Circulating innate and adaptive immunity against anti-Haemophilus influenzae type b.

Haemophilus influenzae type b (Hib) are one of most dangerous microbes that occupies the paediatric nasopharyngeal as a commensal opportunistic bacterium, which may lead to meningitis in uncontrolled infection. Colonisation of pharyngeal tissues is the starting point for most H. influenzae infections, which may develop into invasive diseases, such meningitis. The vaccination against Hib in specific, as well as against most of vaccines preventable diseases; in general, play a major role in reducing children (< 5 years old) Hib meningitis from 57/100,000 to the lowest known Hib meningitis incidents in the history. First invented Hib vaccine was licensed in 1985 and contained Hib capsular polysaccharide (CPS); afterward, conjugate vaccines have been innovated and licensed on the road to improve Hib vaccine efficacy. Polyribosylribitol phosphate (PRP) is the main vaccine unite structure. Since anti-CPS antibodies in the serum reflect the extent of the acquired immunity against Hib infections, the concentration of ⩾ 0.15 g/ml of anti-CPS is believed to be an indicator for short-term protection from invasive Hib diseases, whereas one-month post-completion of primary Hib immunization concentration of ⩾ 1.0 g/ml is trusted to be immunological protective. As considered that serum anti-CPS antibodies are effectively linked to protection, the evaluation of antibodies concentration and reconsideration of published worldwide populations antibodies concentration are consider vital strides on the way to accurate valuation of Hib immunity that induced by vaccination; either direct or herd. As documented, some populations; worldwide, still susceptible to invasive Hib infections. Several populations worldwide remain vulnerable to Hib-related infections. We believe that up-to-date review article regarding circulated Hib immunology, represented in anti-Hib antibodies and worldwide Hib incidences will provide a precious information for microbiologists, public health officials, epidemiologists, immunologists, and strategic preventive healthcare executives.

Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis.

BACKGROUND: Oral glycerol reduces severe neurologic sequelae in childhood bacterial meningitis, but the mechanism awaits elucidation. We conducted a prospective, randomized, double-blind study in which the effects of glycerol and intravenous dexamethasone were compared with placebo recipients in an intensive care setting in India. METHODS: Thirty-six children at age 2 months to 12 years with meningitis were treated with ceftriaxone and were randomized to receive also either dexamethasone intravenously, or glycerol orally, or both agents, or neither. The illness was monitored with preset criteria. The primary outcome measures were the changes in plasma osmolality and in urine output. RESULTS: Nine children received glycerol, 8 dexamethasone, 11 both agents, and 8 only placebo. The leading agents identified were Streptococcus pneumoniae, Haemophilus influenzae type b, and Staphylococcus aureus. Only the glycerol recipients increased plasma osmolality by up to 3% from the mean baseline of 294 mOsm/kg in the glycerol and 295 mOsm/kg in the glycerol-dexamethasone group. This change occurred within 6 hours, the critical period of treatment, and lasted <24 hours. Blood pressure was not affected, nor did urine output increase. The dexamethasone-only and placebo-only recipients showed immediate decrease in serum osmolality. CONCLUSIONS: Because excretion of the cerebrospinal fluid is inversely associated with plasma osmolality, we suggest that the glycerol-induced osmolality increase reduce the volume of cerebrospinal fluid, enhanced water movement back to the plasma by osmosis, increased cerebral blood flow, and thus, improved brain oxygenation.

The paradox of Hemophilus infuenzae type B bacteremia in the presence of serum bactericidal activity.

We investigated the role of serum bactericidal activity in Hemophiplus influenzae type b infections in infants with meningitis and in a rat model. In infected infants, 13/22 admission sera had bactericidal activity against the infecting strain, and bacteremia was as frequent in those with bactericidal activity (54%) as those without (56%). The coexistence of bactericidal activity and bacteremia was reproduced and studied in experimentally infected weanling rats. Serum from such rats kills in vitro 95% of conventionally broth-grown bacteria within 10 min, but does not kill organisms obtained from the infected animals. Thus bactericidal activity as conventionally determined for H. influenzae b may have no relevance in vivo, Incubation of broth-grown bacteria in normal rat serum for 30 min at 37 degrees C produces a resistance like that of in vivo organisms. This phenotypic conversion depends on factors that are of molecular weight less than 1,000, stable to 100 degrees C, but destroyed by ashing. When injected intravenously into nonimmune animals, broth-grown bacteria are quickly cleared, while serum-preincubated bacteria are not. The latter, however, are cleared when injected into bacteremic rats (half-life 30 min). Bacteremia in the rats may persist despite this capacity for clearance because bacteria are entering the blood from extravascular fluids, which contain greater than 90% of the total bacterial burden.

Immunization histories given by adult caregivers accompanying children 3-36 months to the emergency department: are their histories valid for the Haemophilus influenzae B and pneumococcal vaccines?

OBJECTIVE: To obtain immunization histories from adult caregivers accompanying children to the emergency department (ED), to determine the accuracy of the caregiver's report for the Haemophilus influenzae B (Hib)and 7-valent pneumococcal vaccine (PCV7). METHODS: This was a prospective, observational study of children age 3 to 36 months presenting to the Albert Einstein Medical Center ED during the period of November 1, 2004, through January 31, 2005. Caregivers were asked to complete a questionnaire about their child's immunization status and if the child's vaccinations were up-to-date. Immunization records were obtained from the child's most recent primary care physician (PCP) to determine whether the caregiver's report was correct for PCV7 and Hib. Children were considered delayed if they were more than 30 days past due date for one or both vaccines according to the PCP records. RESULTS: Of 205 PCP offices contacted, we were able to obtain 173 immunization records for our analysis. Examination of vaccine records showed that 109 (63.0%) of the 173 children were up-to-date on both immunizations. When the child's caregiver was asked if shots were up-to-date, 159 (91.9%) of 173 said that all shots were given, and only 14 (8.1%) of 173 reported being behind schedule. Of the adults reporting the child up to date, 105 (66.0%) of the 159 children were confirmed to be up-to-date. Thus, 34.0% of caregivers were incorrect in stating that their child's immunization status was up-to-date for both these vaccines. CONCLUSIONS: Caregiver report was determined to be inaccurate for Hib and PCV7. Despite 91.5% of caregivers stating that shots were up-to-date, only 66.0% were correct that their child was up-to-date with these 2 vaccines. The ED physician should use caution in making clinical decisions based on the history given by a caregiver regarding their child's immunization status.

Meningitis in an adult caused by Hemophilus influenzae, biotype III.

An elderly woman had an abrupt onset of symptoms consistent with bacterial meningitis without an obvious source of infection. The organism, isolated from the blood and CSF, was a nonserotypeable Hemophilus influenzae, biotype III. To our knowledge, this is the first reported case of meningitis caused by this organism.

Serum C-reactive protein as detector of pretreated childhood bacterial meningitis.

Serum C-reactive protein (CRP) levels were measured at presentation to the hospital in 15 children with proven bacterial meningitis (BM) pretreated with antibiotics. CRP exceeded the upper normal limit of 19 mg/l in all cases; the mean value was 195 mg/l (range, 55 to 375 mg/l). On the other hand, CRP levels were normal in 12 patients with viral meningitis or meningoencephalitis. Rapid determination of serum CRP should be performed whenever BM is suspected.

Anemia with Haemophilus influenzae meningitis.

The hematologic values in patients with Haemophilus influenzae meningitis were contrasted with those of patients with other types of bacterial meningitis and aseptic meningitis in an attempt to determine whether anemia is either specific for or more common in patients with H influenzae meningitis. Patients with H influenzae meningitis had significantly lower admission hemoglobin values because they were significantly younger than the other two groups. The H influenzae meningitis patients with the lowest hemoglobin values on admission had been sicker for longer periods prior to diagnosis and had higher initial white cell counts. Patients with H influenzae meningitis, aged 3 to 24 months, developed lower hemoglobin values during hospitalization than did patients with other forms of meningitis. Anemia occurs with all forms of bacterial meningitis but is uncommon in aseptic meningitis. The anemia observed in patients with H influenzae meningitis, particularly those less than 2 years of age, is generally more severe than that observed in other forms of bacterial meningitis.

Pathogenesis of Haemophilus influenzae meningitis.

The hypoxia induced by decreased cerebrocortical blood flow contributes to the neurologic deficits found in many survivors of Hib meningitis. Because reduced blood flow is measurable within 48 hours of acquisition of bacteria, the inability of antibiotic therapy to prevent sequelae is more easily understood insofar as damage has already occurred by the time treatment is initiated. Hydrocephalus is probably due to severe choroid plexus necrosis with aqueductal occlusion. These deficiencies, along with the neuronopathy, contribute to permanent cerebrocortical deficits, including impaired learning ability.

Interleukin 6 activity in infants and children with bacterial meningitis. The Collaborative Study on Meningitis.

Concentrations of interleukin 6 (IL-6) in cerebrospinal fluid (CSF) and serum of infants and children with bacterial meningitis were determined and correlations were sought with other indices of inflammation and with outcome. Forty-two patients ages 1 month to 15 years (mean, 2.5 years) were studied. IL-6 activity was detectable (greater than 50 units/ml) in 30 of 36 CSF samples collected at admission from patients with meningitis and in 1 of 23 controls with fever and normal CSF findings. Mean values were 36,000 units/ml (range, 151-156,000). IL-6 activity in CSF persisted during the first 5 days of illness. IL-6 concentrations at admission were not associated with clinical findings, CSF leukocyte, protein and glucose concentrations, serum C-reactive protein concentration and neurologic complications or sequelae. IL-6 was also detected in the serum of 3 of 14 patients with meningitis and in 0 of 7 controls with no infectious disease. The presence of IL-6 was not associated with bacteremia or with duration of fever before admission. The presence of IL-6 in the CSF of pediatric patients with bacterial meningitis is in accordance with available data on other cytokines and suggests their role as mediators of meningeal inflammation.

Fulminating haemophilus influenzae b meningitis.

Haemophilus influenzae type b (HIb) is the most common cause of bacterial meningitis in children with a mortality rate ranging from 1.6% to 14%. Most patients have a 2-3 day history of symptoms prior to admission. A few have fulminating disease with rapid neurological deterioration. Review of 191 cases of HIb meningitis revealed a mortality rate of 2.1% but all who died had fulminating meningitis (FM). Four of six patients with FM died. FM patients had symptoms for less than 24 hours before rapid neurological deterioration with increased ICP, seizures, coma and/or respiratory arrest. Review of 10 FM cases revealed that on admission, 5 had hypotension, 3 had thrombocytopenia, and 8 had coma. Typical CSF changes were seen in only 7. All fatal cases died within 24 hours. Brain swelling and tonsillar herniation were found at autopsy. SDS-PAGE outer membrane protein subtyping did not show one "killer strain". Animal and autopsy data suggest that diminished CSF outflow and cerebral edema contribute to increased ICP. To improve survival of FM patients, initial treatment must (1) decrease ICP below levels impairing cerebral perfusion, (2) maintain adequate ventilation and blood pressure, and include (3) LP when stable, (4) antibiotics, and (5) close monitoring. Utilizing these principles, two FM patients survived without major sequelae.

Thrombocytosis in children with Hemophilus influenzae meningitis.

A retrospective study of thrombocytosis in children with Hemophilus influenzae meningitis was performed. Forty-five percent of patients had a platelet count greater than 500 X 10(9)/l during hospitalization. The mean platelet count was 284 X 10(9)/l on admission, and gradually increased to 648 X 10(9)/l on day 11 of hospitalization. These results document that thrombocytosis is common among children with H. influenzae meningitis and suggest that it is probably a recovery phenomenon.

[Pharmacokinetics of ceftazidime in the cerebrospinal fluid]. / Pharmacocinétique de la ceftazidime dans le liquide céphalorachidien.

A compound potentially effective in the treatment of meningitis should reach high concentrations in CSF. In animal experimental models, ceftazidime levels of 5-25 micrograms/ml were demonstrated during administration of doses generating serum levels similar to those achieved in humans. Human studies later confirmed CSF levels of 5-10 micrograms/ml in patients with meningitis. Ceftazidime CSF kinetic properties are adequate for use of this compound in patients with meningitis due to susceptible organisms.

[Rapid diagnosis of the type of meningitis (bacterial or viral) by the assay of serum procalcitonin]. / Diagnostic rapide du type de méningite (bactérienne ou virale) par le dosage de la procalcitonine sérique.

OBJECTIVE: It has been shown that serum procalcitonin (PCT) can be used to differentiate bacterial from viral meningitis in children in all cases. The aim of this study was to demonstrate the interest of PCT in the management of suspected meningitis in adults. PATIENTS AND METHODS: We conducted a prospective study including 179 consecutive patients admitted to the emergency department for suspected meningitis. All samples were taken at patient admission. The discriminant potential between bacterial and viral meningitis was studied for cerebrospinal fluid parameters (cytology, protein, glucose, lactate) and serum parameters (C reactive protein, PCT). RESULTS: Thirty-two patients had bacterial meningitis, 90 had viral meningitis and meningitis was ruled out in 57. Among all studied parameters, the most discriminant for distinguishing between bacterial and viral meningitis in 100% of the cases proved to be serum procalcitonin with a threshold value of 0.93 ng/ml. CONCLUSION: Serum procalcitonin is an interesting parameter in the emergency department for management of meningitis suspicion in adults.

Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil.

Following routine childhood vaccination against Haemophilus influenzae type b (Hib) disease in Brazil in 1999, passive laboratory surveillance reported increasing numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from meningitis cases. To characterize this increase, we analyzed data on 3910 H. influenzae isolated from cerebrospinal fluid or blood from meningitis cases that were sent to the national reference laboratory for serotyping from 1990 to 2008. Hib accounted for 98% of H. influenzae meningitis isolates received during 1990-1999 versus 59% during 2000-2008, while non-b serotypes increased from 1% to 19% and NTHi increased from 2% to 22% of H. influenzae isolates received during the two periods. Higher proportions of non-b serotypes and NTHi than Hib were isolated from blood rather than cerebrospinal fluid. Estimated incidence rates for H. influenzae meningitis for Sao Paulo state remained below 1 case per million population during 2000-2008, although annual incidence of NTHi meningitis (mean, 0.03 cases per 100,000 population) increased in several age groups. Changes in surveillance for H. influenzae following introduction of Hib conjugate vaccine likely contributed to increased numbers of non-b and nontypeable H. influenzae meningitis isolates received at the national reference laboratory.

Serologic responses of children with meningitis due to Haemophilus influenzae type b.

The immunologic responses of 100 children hospitalized with meningitis due to Haemophilus influenzae type b were measured by the bactericidal antibody assay (BAA) and radioimmunoassay (RIA) for detection of antibody. Short-term (14-17 days after onset of illness) responses were detected by RIA alone in 20 children, by BAA alone in six, and by both tests in 23. The more sensitive RIA detected 20 children who would have been labeled "immunologically unresponsive" had only BAA been used. The magnitude of the antibody response was clearly related to age. Of 26 children with no immediate antibody response, 11 still had no rise in titer of antibody when restudied two to 20 months later; the remaining 15 had subsequent increases in titer. Nine of 10 children who showed an immediate antibody response remained positive when additional blood smaples were taken two to 18 months later. Over half of the children initially unresponsive to H. influenzae type b meningitis subsequently developed specific antibodies. The remainder, who failed to acquire detectable antibodies at either the acute stage of illness or late in convalescence, deserve further investigation as to the nature of their immunologic hyporesponsiveness to H. influenzae type b meningitis.

White blood cell count, erythrocyte sedimentation rate and serum C-reactive protein in meningitis: magnitude of the response related to bacterial species.

White blood cell count (WBC), erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) were determined upon diagnosis of 61 children with bacterial meningitis in order to compare the responses evoked by different bacteria. The age of the patients and the duration of their symptoms were similar in all groups. WBC and ESR corresponded significantly with the bacterial species. The mean WBC in Haemophilus influenzae (n = 44), meningococcal (n = 11) and pneumococcal (n = 6) infection were 14,605/microliters 19,391/microliters and 23,833/microliters, respectively (for H. influenzae and pneumococci p less than 0.001). The mean ESR varied from 58 mm/h (meningococci) to 100 mm/h (pneumococci) (p less than 0.025). CRP was the test least influenced by the nature of the bacteria. The characteristics of CRP suggest its superiority over WBC and ESR as a detector of bacteremic infections. WBC is unsuitable for screening of systemic H. influenzae disease.

Two-dimensional electrophoresis analysis of human serum proteins during the acute-phase response.

The serum of patients with meningitis, due to infection by Haemophilus influenzae type b, was analyzed. Several known acute-phase proteins were separated by two-dimensional electrophoresis and estimated quantitatively. In addition, hitherto undescribed reactants were recognized. Gels were calibrated and relevant spots related to master spot numbers in the human serum protein database.

Lipoprotein alterations in children with bacterial meningitis.

Abnormalities in serum lipids, including hypertriglyceridemia, are common during infectious disorders. However, the lipoprotein pattern during infections, particularly in children, has been investigated to only a limited extent. We have monitored alterations in serum lipoproteins in eight children with a severe bacterial infection (meningitis) by a quantitating method measuring cholesterol and triglycerides in each major class. The levels of triglycerides in serum and in low-density lipoproteins were markedly elevated during the infection, whereas the amount of cholesterol in high-density lipoproteins was decreased. The cholesterol to triglyceride ratio was decreased in low-, as well as in high-density lipoproteins. These lipoprotein abnormalities may, at least in part, be explained by a depressed lipolytic activity of lipoprotein lipase, the key enzyme for removal of triglycerides in man. Serum triglycerides and the levels of cholesterol in high-density lipoproteins, as well as the ratio between these parameters, may be used as indicators of inflammatory activity.