Untreated Meningitis Research Articles

A study of clinico-bacteriological profile and to determine incidence of meningitis in late onset sepsis in newborn unit of tertiary care teaching hospital in Northern India

Background: The daily risk of mortality in first 4 weeks of life is almost 30-fold higher than post-neonatal period. Late onset sepsis (LONS) and meningitis still continue to be major causes of mortality and morbidity in newborn period. Our study was done to study clinical profile of enrolled newborns with LONS along with incidence of meningitis in them. The objective of this study was to study clinico-bacteriological profile and to determine associated incidence of meningitis in neonates with late onset sepsis (LONS) in a hospital setting in Northern India.Methods: It was a hospital based prospective observational study conducted over a period of 12 months enrolling 122 newborn with >72 hours of age fulfilling inclusion criterias.Results: Out of total 122 enrolled newborn, 37 (30.3%) neonates had meningitis. 71 (58.20%) were of term gestation with majority 61 (50.0%) in age group of 4-7days of life. Incidence of LONS in low birth weight and very low birth weight were 54% and 13.5%. Most commonly seen symptoms in at admission were lethargy, refusal to feed and fever. Blood culture was positive in 45 (36.88%) in neonates with Acinetobacter baumanii, klebsiella pneumonia and Escherichiae coli being most commonly seen organisms. Cerebrospinalfluid (CSF) culture was positive in 4 (10.81%) newborns. Mean duration of hospital stay was 24.75±13.96 days. Mortality in neonatal meningitis was 3 (3.2%).Conclusions: Our study proved that about one third of newborn admitted with LONS also had coexistent meningitis. Thus CSF analysis is a must and it should not be missed as untreated meningitis can be devastating for newborn. Antibiotics must be added as per antibiogram of specified institute.

Cost-effectiveness of expanding childhood routine immunization against Neisseria meningitidis serogroups C, W and Y with a quadrivalent conjugate vaccine in the African meningitis belt.

BackgroundNeisseria meningitidis constitutes a major public health problem among countries in the African meningitis belt. Following regional vaccination campaigns for serogroup A and subsequent increases in protection against this serogroup, non-A serogroups such as C and W now pose significant epidemic threats, particularly in young children.ObjectiveTo evaluate the cost-effectiveness of broadening coverage from conjugate serogroup A to quadrivalent ACWY vaccination.MethodsWe developed a 40-year Markov state transition model with annual cycles to simulate costs and clinical outcomes in children aged 1 to 10 in the 26 countries of the African meningitis belt. The incidence of CWY meningitis cases among an unvaccinated population was held constant at inter-epidemic rates of 50 per 100,000/year and 150 per 100,000/year. The country-specific cost and probability of access to meningitis care, vaccine efficacy, the mortality risk among treated and untreated meningitis cases, the risk of clinical sequelae and their respective disability weights were based on published sources. Vaccination cost was based on international prices lists, presented in 2014 US$.ResultsAt an incidence rate of 50 per 100,000/year, routine conjugate vaccination is highly cost-effective in 14 out of 26 countries with a cost/DALY averted ranging from US$555-US$787. At the higher incidence rate of 150 per 100,000/year, quadrivalent vaccination is cost-effective in all 26 countries with a cost/DALY averted ranging from US$105-US$250. The annual incidence rate at which routine conjugate quadrivalent vaccination is expected to be economically justifiable ranges from 13 per 100,000/year in Nigeria to 142 per 100,000/year in Burundi.ConclusionRoutine quadrivalent conjugate vaccination against Neisseria meningitidis is cost-effective at incidence rates well below the epidemic threshold among children living in the African meningitis belt.

Amoxicillin-induced aseptic meningoencephalitis

Meningitis is usually produced by an infectious agent, but there are multiple noninfectious causes. Drug-induced aseptic meningitis (DIAM) is an important entity and has been reported as an uncommon adverse reaction with numerous agents. Thus, DIAM constitutes a diagnostic and patient management challenge. We present a patient with three episodes of aseptic meningitis due to amoxicillin, and then review the literature on this rare idiosyncratic event which may occur after local or systemic drug administration. A 77-year-old man was admitted to our hospital with fever, headache, and neck stiffness. Seven days before admission he had a dental and gingival inflammation. He was treated with two oral doses of 500 mg daily of amoxicillin for one week. The seventh day he awoke with the complaints that prompted hospital admittance. Amoxicillin was stopped 1 day before his admission. From his history we knew of two similar episodes: The first episode was after a dental procedure 3 months before this incident. He had received a 1-week course of postprocedure amoxicillin of 500 mg daily and had similar headache, fever, and chills during the entire course of treatment. He wasn't admitted to the hospital, because he stopped taking amoxicillin and he felt spontaneous pain relief after taking symptomatic pain treatment. The second episodes was 6 months after his first admission, he had been admitted to our hospital with the same symptoms. Amoxicillin was stopped and changed with intravenous (IV) ceftriaxone (CTRX) for 10 days due to suspected partial untreated meningitis. The patient improved rapidly within 2 days and was discharged from the hospital. On the basis of these three confirmed episodes of meningitis after recurrent exposure to amoxicillin, with repetitive negative testing for viral, bacterial, and mycobacterial micro-organisms, we diagnosed aseptic meningitis induced by amoxicillin. To our knowledge, this is the seventh well documented publication of such a severe side effect of a commonly used antibiotic.

Routes, dynamics, and correlates of cochlear inflammation in terminal and recovering experimental meningitis

To examine the routes, dynamics and correlates of cochlear inflammation in meningitis to provide information on the pathogenesis of the associated hearing loss and indications for rational pharmacotherapeutical intervention. A well-established rat model of Streptococcus pneumoniae meningitis was employed. Eight rats were inoculated intrathecally and not treated, whereas 26 were inoculated and treated with ceftriaxone. Six rats were sham-inoculated, making a total of 40 rats. The rats were sacrificed when reaching terminal illness or after 7 days, followed by light microscopy. Routes of cochlear inflammatory infiltration were examined. The volume fraction of inflammatory infiltration was estimated and correlated to bacterial and leukocyte counts in cerebrospinal fluid (CSF) and blood. The perilymphatic space was infiltrated with inflammatory cells via cochlear aqueduct, whereas the endolymphatic space was infiltrated from the spiral ligament. Rosenthal's canal was infiltrated through osseous spiral lamina canaliculi. In the untreated group, the degree of inflammation correlated with time of death, whereas antibiotic treatment reversed this development. Perilymphatic inflammation correlated significantly with the CSF leukocyte count, whereas endolymphatic inflammation correlated with spiral ligament inflammation. Meningogenic inflammation of the rat cochlea occurs via the cochlear aqueduct and the spiral ligament capillary bed. The spiral ganglion is infiltrated through the osseous spiral lamina. The degree of inflammation correlates positively with time of death in untreated meningitis, whereas antibiotic treatment leads to subsiding infiltration during recovery.

Role of leukocytes in cerebral autoregulation and hyperemia in bacterial meningitis in rabbits.

The effect of leukocytes on regional cerebral blood flow (rCBF) and cerebrovascular autoregulation in experimental meningitis was determined in rabbits. Four groups of animals were studied. Cerebrospinal fluid (CSF) leukocyte migration was prevented in two groups by pretreatment with 1.5 mg/kg of IB4, a monoclonal antibody directed against CD11/18 leukocyte adhesion receptors. Intracisternal inoculation was performed with saline (control and control-IB4 groups) or Haemophilus influenzae type b (Hib and Hib-IB4 groups). Eighteen hours later, rCBF was determined with radiolabeled microspheres. Autoregulation was assessed by graded hemorrhagic hypotension. Compared with untreated meningitis (Hib group), IB4-pretreated meningitis (Hib-IB4 group) was associated with a reduced CSF leukocyte count (1,980 +/- 880 vs. 200 +/- 110 cells/microliter; P < 0.05) and an elevated CSF colony count (2.87 +/- 0.08 vs. 5.63 +/- 0.72 log10colony-forming units/ml; P < 0.05). Compared with control, baseline CBF was elevated in both untreated and IB4-pretreated meningitis (51 +/- 2, 54 +/- 2, 66 +/- 5, and 102 +/- 17 ml.100 g-1.min-1 in control, control-IB4, Hib, and Hib-IB4 groups, respectively). The degree of hyperemia in meningitis was related to the CSF colony count, with a high CBF occurring in animals with high colony counts. During hypotension, CBF remained at or above baseline in the Hib group and both control groups, indicating preservation of cerebrovascular autoregulation in untreated Hib meningitis. In the Hib-IB4 group, the elevated baseline CBF was not maintained during hypotension, falling to 51% of baseline at a cerebral perfusion pressure of 30 mmHg and indicating impairment of cerebrovascular autoregulation. These results suggest that CSF leukocytes are not primarily responsible for the hyperemic response in Hib meningitis. Cerebral hyperemia may be induced either directly by bacterial components or indirectly by components of the inflammatory cascade that precede CSF leukocyte migration.

Microvascular Changes during the Early Phase of Experimental Bacterial Meningitis

We investigated the temporal profile of the changes in regional CBF (rCBF) and intracranial pressure (ICP) during the early phase of pneumococcal meningitis in the rat. rCBF, as measured by laser-Doppler flowmetry, and ICP were continuously monitored during 6 h post infection (p.i.). Brain edema formation was assessed by brain water content determinations. Meningitis was induced by intracisternal injection of 75 microliters of 10(7) colony-forming units/ml pneumococci (n = 7). In control animals (n = 6), saline was injected. There was no change in the rCBF or ICP of controls throughout the experiment. However, there was a dramatic increase in rCBF and ICP associated with brain edema formation in untreated meningitis animals. rCBF increased to 135.3 +/- 33.8% (mean +/- SD) in the untreated animals at 1 h p.i. and reached 211.1 +/- 40.5% at 6 h p.i. (p less than 0.05 compared with controls). ICP increased from 2.9 +/- 1.4 to 10.4 +/- 4.7 mm Hg at 6 h p.i. (p less than 0.05 compared with controls). Brain water content was significantly elevated (79.69 +/- 0.24 compared with 78.94 +/- 0.16% in the control group, p less than 0.05). We investigated the effect of dexamethasone (3 mg/kg i.p.), which was given prior to the induction of meningitis (n = 3) or at 2 h after pneumococcal injection (n = 5), indomethacin (10 mg/kg i.v., n = 5), and superoxide dismutase (SOD; 132,000 U/kg i.v. per 6 h, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

The half-hour synthetic 1–24 corticotropin testof adrenocortical reserve in children

Stimulation of the adrenal cortex by intravenous administration of synthetic 1–24corticotropin can be utilized as a rapid and economical means for assessing adrenocortical reserve in children. Since the test can be performed in 30 minutes, adrenal function in rapidly changing clinical conditions can be studied, and iatrogenic adrenocortical suppression more easily monitored. The present study reports the plasma 17-hydroxycorticosteroid responses of 9 normal control children, 6 1/2 to 12 years of age, to both 1–24 corticotropin and saline infusions and also describes the responses of 17 patients requiring adrenocortical evaluation and of 5 children with untreated meningitis. The synthetic corticotropin was a reliable stimulator of a rise in plasma 17-hydroxycorticosteroid levels. Among the 5 children with meningitis, 3 had a fivefold increase in resting plasma 17-hydroxycorticosteroid levels, in comparison with the concentrations in nonstressed individuals and responded to synthetic corticotropin with a further elevation of 17-hydroxycorticosteroid. Two patients with a ninefold elevation of resting plasma levels failed to respond to corticotropin. These results give no indication of adrenocortical insufficiency but suggest the upper limits of response during stress.

LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS

1. In experimental Type I pneumococcal meningitis of dogs central cord involvement is common after the 2nd day of the disease. 2. These central cord lesions may progress toward extensive suppurative myelitis. 3. Abscesses are infrequent; they arise either as direct perivascular extensions of the meningeal disease or at the site of infected purpuric lesions. 4. In prolonged untreated meningitis of reinfected animals, nothing resembling the disappearance of exudate following crisis in pneumonia occurs. The tendency is toward organization. 5. Late lesions are characterized by the marked development of a perivascular clasmatocytic apparatus, similar to, but more extensive than that hitherto reported in experimental herpetic encephalitis.