Invasive Haemophilus influenzae Type b Disease in the Post Hexavalent Era: Ten Years of Molecular Surveillance in Tuscany.

BACKGROUND: The epidemiologic characteristics of invasive Haemophilus influenzae type b disease (HIBD) have markedly changed since the introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine worldwide. The immunization schedule against Haemophilus influenzae type b differs in Europe. METHODS: This is a retrospective observational study which evaluates all the data included in the molecular surveillance register for invasive infectious diseases at the Laboratory of Molecular Diagnosis at Meyer Children's University Hospital from December 2008 to December 2018 with a diagnosis of invasive HIBD in children <5 years of age. RESULTS: We identified 4 cases of HIBD: all the cases presented signs or symptoms of invasive infection and the H. influenzae type b was identified in cerebrospinal fluid, or blood or bronchoalveolar lavage by molecular test. The crude incidence for Hib invasive disease in Tuscany is 0.26/100,000 p-y in children younger than 5 years, significantly different from the incidence rate before the introduction of the Hib vaccination. Vaccination effectiveness can be estimated at 97.9% and the impact of hexavalent (2p+1) vaccine at 99.6%. CONCLUSIONS: This work confirms the high impact of the hexavalent vaccine 2p+1 schedule for HIBD in children <5 years, emphasizing the role of molecular test for HIBD diagnosis and surveillance.

Invasive Haemophilus influenzae Disease at Texas Children's Hospital, 2011 to 2018.

BACKGROUND: Universal vaccination with Haemophilus influenzae type b conjugate vaccines has significantly changed the epidemiology of invasive H. influenzae disease in the United States. We reviewed the epidemiology, clinical features, and outcomes in 61 patients with invasive H. influenzae disease evaluated at Texas Children's Hospital (TCH). METHODS: Cases of invasive H. influenzae disease, defined as isolation of the organism from cerebrospinal fluid, blood, synovial fluid or pleural fluid, during 2011 to 2018 among children cared for at TCH in Houston, TX, were included. RESULTS: We identified 61 cases of invasive H. influenzae disease in children ≤18 years of age. The overall hospitalization rate due to invasive H. influenzae disease increased between 2011 and 2018 (0 vs. 0.64/1000 hospitalizations; P = 0.019). The majority (80%) of infections occurred in children <5 years of age. Of the 61 H. influenzae infections, 24 (39.3%) infections were caused by nontypeable H. influenzae strains, 18 (29.5%) infections were caused by H. influenzae type a, 12 (19.7%) infections were caused by H. influenzae type f, 3 (4.9%) infections were caused by H. influenzae type e and 4 (6.6%) isolates were not typed. A total of 78.7% of the isolates were ß-lactamase negative. The most common clinical presentations were bacteremia without a source, pneumonia and meningitis. CONCLUSIONS: The hospitalization rate for H. influenzae invasive disease increased over an 8-year period at TCH. The overall trend was mainly driven by an increasing number of invasive infections caused by nontypeable H. influenzae and H. influenzae type a. Morbidity was substantial, especially in meningitis cases.

ß-Lactam resistance among Haemophilus influenzae isolates in Poland.

OBJECTIVES: Haemophilus influenzae is a human-specific Gram-negative coccobacillus responsible for a significant number of respiratory tract infections and severe invasive infections such as meningitis and sepsis. The purpose of this study was to characterise the mechanisms of ß-lactam resistance among Polish H. influenzae isolates and to evaluate the resistance detection methods applied. METHODS: This study was conducted on 117 Polish H. influenzae isolates collected in 2012. Minimum inhibitory concentrations were assessed by broth microdilution. All strains were evaluated using the disk diffusion method and the algorithm proposed by the Nordic Committee on Antimicrobial Susceptibility Testing (NordicAST). To detect changes in penicillin-binding protein 3 (PBP3), PCR screening was performed, followed by ftsI gene sequencing. RESULTS: Neither ß-lactamase production nor PBP3 alterations were demonstrated in 76 isolates (65.0%). Susceptibility to ampicillin, amoxicillin, amoxicillin/clavulanic acid, cefuroxime (intravenous) and ceftriaxone was observed in 70.9%, 78.6%, 98.3%, 82.9% and 100% of the isolates, respectively. ß-Lactamase production characterised 21 isolates (17.9%). Screening PCR identified 20 isolates (17.1%) with PBP3 alterations, and according to subsequent ftsI sequencing all these strains were finally recognised as gBLNAR (genetically ß-lactamase-negative, ampicillin-resistant), among which 65.0% were ampicillin-resistant. According to molecular classification of PBP3 alterations, 95.0% of gBLNAR belonged to group II, representing four subgroups IIa-IId. CONCLUSIONS: Haemophilus influenzae resistance to antibiotics requires continuous attention, effective detection methods and a rational policy of antibiotic usage. The algorithm proposed by NordicAST can be applied in routine laboratory work, whereas sequencing of the ftsI gene may be useful in molecular epidemiology studies.

Multiplexed instrument-free meningitis diagnosis on a polymer/paper hybrid microfluidic biochip.

Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Haemophilus influenzae type b (Hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. Because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. Herein, we report a polymer/paper hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) for multiplexed instrument-free diagnosis of these three major types of bacterial meningitis, with high sensitivity and specificity. Results can be visually observed by the naked eye or imaged by a smartphone camera under a portable UV light source. Without using any specialized laboratory instrument, the limits of detection of a few DNA copies per LAMP zone for N. meningitidis, S. pneumoniae and Hib were achieved within 1h. In addition, these three types of microorganisms spiked in artificial cerebrospinal fluid (ACSF) were directly detected simultaneously, avoiding cumbersome sample preparation procedures in conventional methods. Compared with the paper-free non-hybrid microfluidic biochip over a period of three months, the hybrid microfluidic biochip was found to have a much longer shelf life. Hence, this rapid, instrument-free and highly sensitive microfluidic approach has great potential for point-of-care (POC) diagnosis of multiple infectious diseases simultaneously, especially in resource-limited settings.

Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis.

INTRODUCTION: Outcomes following bacterial meningitis are significantly improved by adjunctive treatment with corticosteroids. However, little is known about the levels and significance of intrathecal endogenous cortisol. The aim of this study was to assess cortisol as a biological and diagnostic marker in patients with bacterial meningitis. METHODS: Forty-seven consecutive patients with bacterial meningitis and no prior treatment were evaluated. For comparison, a group of 37 patients with aseptic meningitis and a group of 13 healthy control individuals were included. RESULTS: The mean age of the bacterial meningitis patients was 42 years, and the mean Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores on admission were 12, 13 and 4, respectively. Altogether, 40 patients (85%) were admitted to the intensive care unit, with a median (interquartile range) length of stay of 8 (4 to 15) days. A bacterial etiology was confirmed in 35 patients (74%). The median (interquartile range) cortisol concentration in cerebrospinal fluid (CSF) was 133 (59 to 278) nmol/l. CSF cortisol concentrations were positively correlated with serum cortisol levels (r = 0.587, P < 0.001). Furthermore, CSF cortisol levels correlated with Acute Physiology and Chronic Health Evaluation II score (r = 0.763, P < 0.001), Sequential Organ Failure Assessment score (r = 0.650, P < 0.001), Glasgow Coma Scale score (r = -0.547, P < 0.001) and CSF lactate levels (r = 0.734, P < 0.001). CSF cortisol was only weakly associated with intrathecal levels of IL-6 (r = 0.331, P = 0.02) and IL-8 (r = 0.296, P < 0.05). CSF cortisol levels in bacterial and aseptic meningitis significantly differed (P < 0.001). The CSF cortisol concentration of 46.1 nmol/l was found to be the optimal cutoff value for diagnosis of bacterial meningitis. CONCLUSION: CSF cortisol levels in patients with bacterial meningitis are highly elevated and correlate with disease severity. Moreover, our findings also suggest that intrathecal cortisol may serve as a valuable marker in discriminating between bacterial and aseptic meningitis.

Role of the urokinase plasminogen activator system in patients with bacterial meningitis.

BACKGROUND: The urokinase plasminogen activator system has the potency to promote leukocyte recruitment and blood-CSF barrier breakdown, and thus may play an important pathophysiologic role in bacterial meningitis. METHODS: CSF and serum concentrations of urokinase-plasminogen activator (urokinase [uPA]), uPA receptor (uPAR), and PA inhibitor-1 (PAI-1) were quantified by ELISA in 12 patients with bacterial meningitis, control patients (n = 10) with noninflammatory neurologic diseases, and 10 patients with Guillain-Barré syndrome (GBS), a disease in which blood-CSF barrier disruption occurs without CSF pleocytosis. Casein zymography was used to determine PA-dependent plasminogen activation in the CSF. RESULTS: A marked increase in uPA-dependent plasminogen activation was detected in the CSF of patients with bacterial meningitis vs CSF of patients with GBS and controls. Accordingly, ELISA analysis of CSF revealed intrathecal upregulation of uPA protein in patients with bacterial meningitis. CSF concentrations of uPAR and PAI-1 were also elevated in these patients. The serum of patients with bacterial meningitis showed elevated protein levels of uPA, but not uPAR or PAI-1. Positive correlations were found between blood-CSF barrier breakdown and CSF uPA concentrations, and between CSF pleocytosis and CSF/serum ratios of the potent chemokine uPAR in patients with bacterial meningitis. Furthermore, an adverse clinical outcome in these patients correlated with serum uPA concentrations. CONCLUSION: In bacterial meningitis, the urokinase plasminogen activator system is involved in leukocyte recruitment and breaching of the blood-CSF barrier, and this may contribute to an unfavorable clinical outcome.

Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.

Phase variation of lic1A, lic2A and lic3A in colonization of the nasopharynx, bloodstream and cerebrospinal fluid by Haemophilus influenzae type b.

The role of phase variation of lic1A, lic2A and lic3A in the ability of Haemophilus influenzae type b to colonize the nasopharynx, bloodstream and cerebrospinal fluid (CSF) of infants was investigated. This was achieved by using PCR to determine the number of 5'-CAAT-3' repeats present in each gene, which is indicative of whether each ORF can be expressed. Multiple PCR products of different intensities were amplified from all three genes at each site sampled. This indicated that the nasopharynx, bloodstream and CSF were colonized by a heterogeneous population of organisms, expressing different combinations of lic genes. At each site however, a predominant PCR product was amplified from each gene, indicating that organisms with this genotype were the most abundant. The number of 5'-CAAT-3' repeats in this predominant product varied depending upon whether organisms were isolated from the nasopharynx, bloodstream or CSF. These observations suggest that the expression of different combinations of lic genes may influence the efficiency with which H. influenzae colonizes the nasopharynx, bloodstream and CSF of infant rats.

Recurrent meningitis in the pediatric patient--the otolaryngologist's role.

OBJECTIVE: To assess the etiology of recurrent meningitis in the pediatric patient. DESIGN: Retrospective case series and literature review. SETTING: Tertiary-care pediatric hospital. PATIENTS: Children (< 17-years-old) with recurrent meningitis, treated at Texas Children's Hospital (TCH) between 1984 and 1995. RESULTS: A review of 463 cases of bacterial meningitis over an 11 year period revealed six children aged 3 months to 15 years with the diagnosis of recurrent meningitis. The patient's age, number of episodes of meningitis, diagnostic investigations performed and etiologies of recurrent meningitis were recorded. Fifteen episodes of meningitis were identified in these six patients; Streptococcus pneumoniae represented the bacteriology in 73% of the cases. Two patients were diagnosed with temporal bone abnormalities, two children with immunological deficiencies and no underlying etiology for the recurrent meningitis was identified in the remaining two patients. In this series, one-third of patients had an otolaryngologic etiology for their recurrent meningitis. These six patients, along with a review of the recent literature, will highlight the need for otolaryngological assessment and the importance of considering immunological investigations when managing recurrent meningitis in the pediatric patient. CONCLUSION: We propose that children with recurrent meningitis of unknown etiology undergo: (1) an audiological evaluation; (2) a CT scan of the temporal bones, skull base and paranasal sinuses; and (3) an immunological evaluation.

Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis.

We have recently described the induction of anti-cytokine autoantibodies (Aabs) in the serum as a novel mechanism for cytokine regulation during bacterial infections. Here we use the infant rat-model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially important cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-4 and IL-10 were detected at day 3 post-inoculation (p.i.) with maximum induction at day 8. Thereafter, these levels of cytokines had become undetectable. Increased Aab titres to these cytokines, except IL-4, were registered with peak levels between days 7 and 9. Upon re-inoculation with Hib at day 30, regeneration of Aabs was recorded 7 days later (i.e. at day 37). To control the specificity of these Aabs, preincubation of the CSF with a cytokine inhibited the binding effects of that particular cytokine, but not those of any other cytokine. Aabs dose-dependently inhibited IFN-gamma-induced MHC expression by peritoneal macrophages and TNF-alpha-mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti-cytokine antibodies in the CSF of the meningitis Hib model. Furthermore, the data present a role for the Aabs in cytokine regulation, which is consistent with the previously demonstrated effects of the Aabs in the serum.

Differences in N-acetylmuramyl-L-alanine amidase and lysozyme in serum and cerebrospinal fluid of patients with bacterial meningitis.

N-acetylmuramyl-L-alanine amidase (NAMLAA) specifically degrades peptidoglycan, a major component of bacterial cell walls. Lysozyme degrades peptidoglycan differently by hydrolyzing the aminosugar backbone of peptidoglycan. In another study, it was shown that the two enzymes act synergistically to inactivate the inflammatory properties of peptidoglycan. The presence of lysozyme and NAMLAA was determined in serum and cerebrospinal fluid (CSF) of patients with bacterial meningitis. High concentrations of lysozyme were found in CSF while, surprisingly, NAMLAA was not present. To explain this phenomenon, the degranulation pattern of neutrophils in CSF was compared with that of neutrophils from blood. Specific granules contain lysozyme and the azurophil granules contain both lysozyme and NAMLAA. CD66b expression on the cell surface, indicative for fusion of the specific granules with the cell membrane, was higher in CSF than in blood, while the marker for the azurophil granules was lower.

[Examination of primary SPF swine after experimental infection with Haemophilus parasuis. Clinical symptoms, changes in hematological parameters and in the parameters of the cerebrospinal fluid]. / Untersuchungen an primären SPF-Ferkeln nach experimenteller Infektion mit Haemophilus parasuis. Klinische Symptomatik, Veränderungen von hämatologischen Parametern und von Parametern des Liquor cerebrospinalis.

The objectives of this work were to cause the Glässer's disease (GD) in primary specific pathogen free piglets after experimental infection, to observe the clinical symptoms and to examine the influence of the infection on the haematological parameters. GD was caused by experimental infection of Haemophilus parasuis in seven to eight weeks old specific pathogen free piglets. In relation to the infection route the morbidity was high (83-100%) and 20% of the infected piglets died. Based on the physical examination fever, respiratory distress, cramps and paralysis were observed which are typical for GD. Arthritis and nerval symptoms are also typical but less common in Glässer's disease. PCV was significantly decreased and WBC significant increased before the piglets were euthanatized.

Interaction of the capsular polysaccharide of Haemophilus influenzae type B with C1q.

The Gram-negative pleomorphic bacterium Haemophilus influenza type b (Hib) is the most common cause of bacterial meningitis in children below the age of 2. Virtually all infants between 3 and 18 month of age lack anticapsular antibodies. This is typical for the response to a T-cell-independent antigen. 3-5% of this group harbour Hib in the nasopharynx, but the incidence of disease is 1000-fold less. This implicates other factors in host susceptibility in addition to the absence of such antibodies. Under physiological conditions the purified complement subcomponent C1q interacts with polyribosylribitolphosphate (PRP), the capsular polysaccharide of Hib. The complex formation of C1q, the most basic serum protein, with this polyanion was demonstrated by several methods: agarose gel electrophoresis followed by immunoprecipitation in the gel and Coomassie staining; western blot analysis of C1q-PRP complexes; complex formation in electrophoretic separation of PRP; retardation of electrophoretic mobility of PRP was checked by blotting of this polysaccharide. These results were confirmed by time- and dose-dependent alteration of antigenetic properties detected by C1q-Sandwich-ELISA after coincubation with PRP. Preincubation of serum treated Hib with C1q significantly enhanced the O2-metabolism of polymorphonuclear leucocytes in chemiluminescence assay. Infants of the susceptible age group develop antibodies to several Hib outer membrane proteins (OMP) and lipooligosaccharides (LOS) in response to infection. The complement activation by immune complexes might be inhibited by the formation of C1q-PRP complexes. Our results do not support the thesis that C1q can be activated by the interaction with PRP as shown before for other polyanions. Differing C1q to PRP ratios could be a possible explanation for different host susceptibilities.

The epidemiology of Haemophilus influenzae invasive disease in Scotland prior to immunisation.

Immunisation against Haemophilus influenzae b (Hib) was added to the UK childhood vaccination schedule on 1 October 1992. Based on reports of laboratory isolations from blood and/or CSF, the epidemiology of Haemophilus influenzae invasive disease in Scotland during the last full year before immunisation (1991) is reviewed. In children aged under five years the estimated incidence of infection (25.5 per 100,000) is higher than that previously reported from Scotland, but lower than estimates from Glasgow and other UK studies. However, the age-sex and seasonal distribution is consistent with previous surveys. As in England and Wales, there appears to be regional variation in incidence within Scotland, although this may simply reflect differences in the completeness of laboratory reporting. In addition to 113 laboratory reports of H. influenzae invasive infection, a retrospective search of hospital discharge data and death registrations identified a further 51 and two cases respectively, some of whom may be genuine. In spite of reservations about hospital discharge data, this raises the possibility that there may be an element of under-reporting by laboratories. With the advent of record linkage of hospital discharge data, it would be prudent to monitor the impact of the Hib vaccine programme using this data source in addition to laboratory reports and death registrations.

Cortical visual impairment following bacterial meningitis: magnetic resonance imaging and visual evoked potentials findings in two cases.

Cortical visual impairment (CVI) following bacterial meningitis is a very uncommon complication. Two children with CVI following bacterial meningitis are reported. Bacterial agents were Haemophilus influenzae type B in one and meningococci in the other child. Both children showed only insufficient recovery from CVI, mental retardation and residual neurological symptoms. Flash visual evoked potentials (VEP) showed preserved cortical response at onset of CVI. Re-evaluations several months later showed significantly reduced amplitudes, but normal latencies for P100. Thus, flash VEP does not allow prediction of visual outcome. MRI results have not been reported before. MRI at onset of diagnosis showed occipital parenchymal irregularities with enlarged sulci and subarachnoid spaces. Follow up MRI 15 months after onset of CVI in one patient showed marked atrophy of the occipital cortex, hyperintensities of the cortical white matter and no visible optic radiation. The MRI findings indicate hypoxic-ischaemic lesions in the border zone between the distribution of the great cerebral arteries.

Rapid diagnosis of severe Haemophilus influenzae serotype b infections by monoclonal antibody enzyme immunoassay for outer membrane proteins.

A highly sensitive and specific enzyme immunoassay (EIA) for the detection of Haemophilus influenzae serotype b antigens in body fluids and broth cultures was developed, with a polyclonal antibody directed against polyribose phosphate as the solid-phase reagent and a biotinylated monoclonal antibody directed against H. influenzae type b outer membrane protein as the liquid-phase reagent. H. influenzae type b antigens could be detected in broth cultures containing as little as 50 organisms per ml. The sensitivity and specificity of this system were compared with those of two commercial kits and counterimmunoelectrophoresis. The overall detection of H. influenzae type b antigens in clinical specimens collected from children infected with H. influenzae type b was as follows: with Phadebact, 86 and 86% in cerebrospinal fluid and urine specimens, respectively; with Bactigen, 86, 80, and 92%, with counterimmunoelectrophoresis, 78, 73, and 75%, and with biotin-avidin EIA, 100, 100, and 100% for cerebrospinal fluid, serum, and urine specimens, respectively. In the biotin-avidin EIA, no positive reactions were noted in specimens collected from patients infected with other bacteria or from patients without evidence of bacterial infection, whereas false-positive reactions were found by counterimmunoelectrophoresis and the commercial kits. These results suggest that this monoclonal antibody reacting with the outer membrane protein is more specific and sensitive than the conventional methods using polyclonal antisera for the detection of H. influenzae type b antigens during severe infections in children.

Antibiotic susceptibility of Haemophilus influenzae isolated from cerebrospinal fluid and blood.

The emergence of ampicillin and chloramphenicol resistant Haemophilus influenzae type b in Denmark has created demands for alternative treatments of serious infections with H. influenzae. In this study 102 strains of H. influenzae recovered from cerebrospinal fluid (85) and blood (17) were tested for susceptibility to ampicillin, piperacillin, erythromycin, rifampicin, chloramphenicol, cefuroxime, cefotaxime, ceftazidime, ceftriaxone, moxalactam, aztreonam, and netilmicin by means of the agar dilution method. The majority (97%) was H. influenzae type b and of these strains 94% belonged to biotype I. Nine of the investigated strains were beta-lactamase producers. Ceftriaxone and cefotaxime were the most active agents (MIC90 less than or equal to 0.025 microliter/ml) followed by moxalactam and aztreonam (MIC90 = 0.1 microgram/ml). Except for ampicillin and piperacillin, the MIC was similar for beta-lactamase producers and non-producers. Several of the investigated antibiotics, especially some of the third generation cephalosporins, might constitute valid therapeutical alternatives to conventional drugs in the treatment of severe H. influenzae infections.

Experiencia preliminar con la prueba de aglutinación de látex en la detección precoz de haemophilus influenzae tipo B en meningitis aguda bacteriana / Preliminary experience with latex aglutination test for early detection of type B haemophilus influenzae in acute bacterial meningitis

Estudiamos en forma prospectiva 13 pacientes que ingresaron a la unidad de infecciosos del Hospital Dr. Félix Bulnes Cerda en el período de un año (julio 93-julio 84) con el diagnóstico clínico y de laboratorio de Meningitis Aguda Bacteriana. A cada uno de ellos se practicó tinción de Gram, examen citoquímico, cultivo de líquido cefalorraquídeo, hemocultivos y en forma simultánea Bactogen en líquido cefalorraquídeo, sangre y orina, con el objeto de comparar ambas técnicas de laboratorio. En 5 de los pacientes estudiados, se aisló Hemophilus influenzae tipo B, ya sea en L.C.R. o sangre. El resto se distribuyó entre Neisseria meningitidis (2 casos), Streptococo pneumoniae (2 casos), Salmonella typhimurium (1 caso), Streptococo agalactiae (1 caso). En 2 casos no se logró aislar gérmenes. En los pacientes que se obtuvo Haemophilus Influenzae tipo B (5 casos), la prueba de Bactogen fue positiva en todos ellos, ya sea en LCR, sangre y orina. En un caso a pesar que el bactogen fue positivo, el cultivo resultó negativo. Esto se explicaría por el tratamiento antibiótico que recibió el paciente, previo a su ingreso al hospital. En los pacientes con Meningitis Aguda Bacteriana a otros gérmenes, la prueba del Látex fue negativa. No se observaron falsos positivos. Aunque la casuística es pequeña, creemos que la prueba de aglutinación de látex, podría ser de gran utilidad para una rápida orientación diagnóstica, técnica que debe ser confirmada en nuestro medio, con un mayor número de casos