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PubMed1988

Update on bacterial meningitis.

Recently, advances in identifying the etiologic agent, improving antibiotic therapy, and understanding the pathogenesis of complications of bacterial meningitis have been made. The acute and long-term sequelae and their courses have been documented. Acridine orange staining of the cerebrospinal fluid may identify bacteria in children with partially treated meningitis when gram-staining is not helpful. Monoclonal antibodies for meningococcus group B antigen have been developed and may prove useful for testing cerebrospinal fluid. Several newer cephalosporins have been shown to have excellent in vitro activity against the bacteria commonly associated with meningitis. They are indicated in the treatment of infants between 4 and 8 weeks of age, children in septic shock, children with liver disease, and children with infection with gram-negative enteric agents or bacteria resistant to ampicillin and chloramphenicol. Vasculitis and cerebral infarction may result in some of the complications, such as seizures and hemiparesis, noted in children, and their consequences can be documented by various neuroimaging procedures. The prognosis for ataxia is good, while that for sensorineural deafness is poor. The majority of children will have neither intellectual deficits nor difficulty with academic achievement. An effective vaccine against Haemophilus influenzae type b has been developed and is recommended for children between 18 and 60 months of age.

Adolescent↗
PubMedDate not supplied

Influenza a common viral infection among Hajj pilgrims: time for routine surveillance and vaccination.

BACKGROUND: The annual Hajj pilgrimage to Mecca, Saudi Arabia brings over two million people to a small confined area. Respiratory tract infection is the most common disease transmitted during this period. For most of the etiologic agents of upper respiratory tract infections, no vaccine or prophylaxis is available, except for influenza. Yearly influenza vaccination of high-risk groups is recommended, but no special recommendations are available for those performing the Hajj or other similar large congregational activities. Viral surveillance studies are being carried out through more than 100 centers around the world to identify newly emerging viruses. Saudi Arabia is not one of those centers and no routine surveillance takes place. METHODS: Five hundred Hajj pilgrims presenting with upper respiratory tract symptoms from different parts of the world were screened by way of a throat swab for viral culture, including influenza A and B, parainfluenza, respiratory syncytial virus (RSV), adenovirus, herpes simplex virus (HSV), and enteroviruses. Information was collected on age, sex, nationality, smoking habits and upper respiratory tract symptoms. Vaccination status for influenza and meningococcus was obtained by self-declaration, since most pilgrims did not have their vaccination cards with them. Only those with symptoms including at least fever, reported by the patient to be >38.3 degrees C, and/or sore throat were included. Pilgrims with any other symptoms, especially myalgia and fatigue alone, were excluded, since many of the physical chores during the pilgrimage may contribute to such symptoms. RESULTS: Fifty-four patients (10.8%) had positive viral throat cultures. Of these, 27 (50%) were influenza B, 13 (24.1%) were HSV, 7 (12.9%) were RSV, 4 (7.4%) were parainfluenza, and 3 (5.6%) were influenza A. No enteroviruses or adenoviruses were detected, and no multiple infections were detected. Only 22 (4.7%) pilgrims received the influenza vaccine. When the results are applied to the total number of pilgrims in 2003, an estimate of 24,000 cases of influenza is obtained. CONCLUSION: The findings from this study suggest a high incidence of influenza as a cause of upper respiratory tract infection among pilgrims, estimated to be 24,000 cases per Hajj season, excluding those becoming ill from contact with Hajj pilgrims returning home. They also indicate a very low vaccination rate for the influenza vaccine; as well as poor knowledge of its existence. Continued surveillance during the Hajj pilgrimage is necessary. The influenza vaccine should be a priority for those attending the Hajj pilgrimage, and should also be considered for antiviral prophylaxis.

Adolescent↗
PubMed1991

Development of a protocol for early treatment of endemic meningitis in children in Vanuatu.

Meningitis is endemic in Vanuatu and other Pacific island countries and has a high case fatality rate. The incidence in the southern island of Tanna is especially high. This descriptive study of 64 cases in children (under 15 years) on that island was undertaken over a 21-month period from January 1988 to September 1989. Meningococcus was identified in 23 cases (36%) and Pneumococcus in 12 (19%). The age distribution showed a high rate in under 1 year olds. The symptoms of fever, convulsion and vomiting were most common. Bulging fontanelle (in children under 1 year), neck rigidity, and altered level of consciousness were the most frequent signs. These signs were as frequent in meningococcal as pneumococcal infections and were used to develop a simple protocol for use in primary care. Delay in treatment or referral because of patients seeking traditional medicine is a major problem yet to be overcome. Only a weak association between admissions with meningitis and underweight or crowding was found in this study.

Adolescent↗
PubMedDate not supplied

The impact of new technologies on vaccines.

Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these efficiently in plants. These recombinant antibodies are opening out an era of highly specific and safe therapeutic interventions. Human recombinant antibodies would be invaluable for treating patients with terminal tetanus and rabies. Antibodies are already in use for treatment of cancer, rheumatoid arthritis and allergies. An advantage of preformed antibodies directed at a defined target and given in adequate amounts is the certainty of efficacy in every recipient, in contrast to vaccines, where the quality and quantum of immune response varies from individual to individual.

Animals↗
PubMed1977

[Recurrent meningococcal menigitis and congenital cerebrospinal fluid rhinorrhea].

In a 20-year old patient there were 5 relapses of meningococcus meningitis during a period of 14 years following the first illness. The development of the last relapse was atypical. A congenital cranio-nasal fistula and liquorrhea was found, inflammatory changes in the lumbar and nasal, an expressed cystic-adhesive membrane process during pneumoencephalography. Frequent relapses are connected with a congenital cranio-nasal fistula and a formation of the focus of infection in the membranes of the cerebral base.

Adult↗
PubMed2005

Available carbon source influences the resistance of Neisseria meningitidis against complement.

Neisseria meningitidis is an important cause of septicaemia and meningitis. To cause disease, the bacterium must acquire essential nutrients for replication in the systemic circulation, while avoiding exclusion by host innate immunity. Here we show that the utilization of carbon sources by N. meningitidis determines its ability to withstand complement-mediated lysis, through the intimate relationship between metabolism and virulence in the bacterium. The gene encoding the lactate permease, lctP, was identified and disrupted. The lctP mutant had a reduced growth rate in cerebrospinal fluid compared with the wild type, and was attenuated during bloodstream infection through loss of resistance against complement-mediated killing. The link between lactate and complement was demonstrated by the restoration of virulence of the lctP mutant in complement (C3(-/-))-deficient animals. The underlying mechanism for attenuation is mediated through the sialic acid biosynthesis pathway, which is directly connected to central carbon metabolism. The findings highlight the intimate relationship between bacterial physiology and resistance to innate immune killing in the meningococcus.

Animals↗
PubMed2003

Direct-test PCR for detection of meningococcal DNA and its serogroup characterization: standardization and adaptation for use in a public health laboratory.

A direct PCR test (DT-PCR) was established to detect Neisseria meningitidis DNA in clinical samples from patients with suspected bacterial meningitis. Specific primers for the 16S rDNA of N. meningitidis were designed to amplify a 600 bp DNA fragment. One hundred and ninety-three clinical samples were analysed, corresponding to 114 samples from patients diagnosed as positive and 79 as negative for infection by N. meningitidis using conventional methods (culture, latex agglutination and counterimmunoelectrophoresis). These samples were submitted to PCR by two different clinical sample preparation approaches (with and without DNA extraction and purification) and submitted to different PCR protocols to improve the results. In agarose gel detection, the sensitivity value for DT-PCR was 88.5 % and, using dot-blot DNA detection, the sensitivity increased to 96.4 %. The detection limit for meningococcus in cerebrospinal fluid was 2x10(2) c.f.u. ml(-1). Serogroup prediction was done using a multiplex PCR protocol and the sensitivity was 83 % for agarose gel DNA detection and 96.4 % using dot-blot DNA detection.

Cerebrospinal Fluid↗
PubMed1997

Meningococcal disease in Africa.

Neisseria meningitidis (the meningococcus) is responsible for endemic and meningococcal disease in Africa. Meningococci are placed into 12 serogroups based on their capsular polysaccharide antigens. Group-B meningococci are responsible for sporadic endemic disease. In the meningitis belt of sub-Saharan Africa, the large spreading epidemics which occur every 5-10 years are usually caused by group-A meningococci, with attack rates of 400-500/100,000 population. In the last epidemic, infection spread from the original meningitis belt to Kenya, Uganda, Rwanda, Zambia and Tanzania. Most cases of meningococcal disease are of meningitis and meningococcal septicaemia is a rare presentation except in South Africa. It is important to exclude meningococcal septicaemia since this carries the highest mortality (up to 75%). Treatment involves intravenous chloramphenicol (or intramuscular, oily chloramphenicol), a drug which is preferable to penicillin because penicillin-resistant meningococci have already emerged in Africa. Dexamethasone treatment of meningococcal meningitis is unproven and may even be deleterious in developing countries. Prevention of epidemic meningococcal disease could be achieved by mass vaccination with protein-conjugate, group-A and -C polysaccharides, but these new vaccines are likely to be expensive.

Adult↗
PubMed2005

Are antibodies to the capsular polysaccharide of Neisseria meningitidis group B and Escherichia coli K1 associated with immunopathology?

As polysialic acid (PSA), the capsule of Group B meningococcus (GBM) and Escherichia coli K1, is a component of mammalian glycopeptides, there is concern that vaccines against PSA could induce immunopathology. Purified PSA is not immunogenic; however, as a component of bacteria or bound to proteins, it induces protective antibodies. In this review, we did not unearth data indicating an association of IgG anti-PSA with immunopathology in experimental animals or humans. We found no increased incidence of autoimmunity from GBM infections in our review of the natural history/sequellae of Neisseria meningitis infections. Accordingly, we propose that clinical trials of PSA conjugate vaccines, be considered.

Animals↗
PubMed2002

Replication of Neisseria meningitidis within epithelial cells requires TonB-dependent acquisition of host cell iron.

Neisseria meningitidis (meningococcus [MC]) is able to enter and replicate within epithelial cells. Iron, an essential nutrient for nearly all organisms, is an important determinant in the ability of MC to cause disease; however, its role in MC intracellular replication has not been investigated. We analyzed the growth of MC within the A431 human epithelial cell line and the dependence of this growth on iron uptake. We present evidence here that chelation of iron from infected tissue culture cells with Desferal strongly inhibited intracellular replication of wild-type (wt) MC. We also provide genetic evidence that iron must be acquired by MC from the host cell in order for it to replicate. An hmbR mutant that is unable to use hemoglobin iron and could not grow in tissue culture media without iron supplementation replicated more rapidly within epithelial cells than its wt parent strain. An fbpA mutant that is unable to utilize human transferrin iron or lactoferrin iron replicated normally within cells. In contrast, a tonB mutant could not replicate intracellularly unless infected cultures were supplemented with ferric nitrate. Taken together, these findings strongly suggest that MC intracellular replication requires TonB-dependent uptake of a novel host cell iron source.

Bacterial Proteins↗
PubMed2001

Generation and characterization of a PhoP homologue mutant of Neisseria meningitidis.

Two-component regulatory systems are important regulators of virulence genes in a number of bacteria. Genes encoding a two-component regulator system, with homology to the phoP/phoQ system in salmonella, were identified in the meningococcal genome. Allele replacement was used to generate a meningococcal knock-out mutant of the regulator component of this system, and its phenotype was examined. The mutant displayed many differences in protein profiles compared with wild type, consistent with it being a gene-regulatory mutation. Many of the growth characteristics of the mutant were similar to those of phoP mutants of salmonella: it was unable to grow at low concentrations of magnesium and was sensitive to defensins and other environmental stresses. Magnesium-regulated differences in protein expression were abrogated in the mutant, indicating that the meningococcal PhoP/PhoQ system may, as in salmonella, respond to changes in environmental magnesium levels. These results are consistent with the PhoP homologue playing a similar role in the meningococcus to PhoP in salmonella and suggest that it may similarly be involved in the regulation of virulence genes in response to environmental stimuli in the meningococcus. In support of this conclusion, we found the mutant grew was unable to grow in mouse serum and was attenuated in its ability to traverse through a layer of human epithelial cells. Identification of those genes regulated by the meningococcal PhoP may provide a route towards the identification of virulence genes in the meningococcus.

Alleles↗
PubMedDate not supplied

[A modification to the method for determining the antilysozyme activity of meningococcal strains].

A method of determination of antilysozyme activity in the meningococcus strains has been suggested which consisted in preparing the meningococcus strains culture suspension in liquid media with different lysozyme concentration, incubation of mixtures for some time at 37 degrees C determination of residual lysozyme contents with the use of highly sensitive gel bacterial medium.

Carrier State↗
PubMed1975

Meningitis, pneumonitis, and arthritis caused by Neisseria meningitidis group Y.

Neisseria meningitidis subgroup Y, although commonly isolated from the nasopharynx, rarely has caused meningitis in nonmilitary individuals. Meningococcus (serogroup Y) caused pneumonitis, meningitis, and arthritis in a previously healthy woman. Findings from examination of spinal fluid were minimal, but the clinical aspects of the illness were similar to those seen with other meningococcal serotypes.

Adult↗
PubMed1985

Correlation between G2m(n) immunoglobulin allotype and human antibody response and susceptibility to polysaccharide encapsulated bacteria.

To determine whether genetic factors influence the human antibody response to polysaccharides, we correlated Ig allotypes with the concentrations of antibody to 14 bacterial capsular antigens in 130 actively immunized Caucasian adults. The 88 individuals possessing G2m(n), an allotype antigen of IgG2 subclass heavy chains, had significantly higher postimmunization antibody levels to Haemophilus influenzae type b (Hib) and 8 of 11 pneumococcal types (P less than 0.05) than the 42 lacking this antigen. For Hib, pneumococcus type 14, and meningococcus group C, an increased response was observed in IgG class but not in IgM or IgA classes of antibody. The G2m(n) positive individuals also had higher preimmunization antibody levels to most polysaccharide antigens. Total IgG2 concentrations were correlated with the mean postimmunization antibody concentrations to pneumococci (P = 0.005), but this correlation was independent of G2m(n) by multiple regression analysis. To determine if the lack of G2m(n) was associated with increased susceptibility to infection, we compared the frequencies of various Ig allotypes in 98 children infected with Hib and 98 matched controls. Caucasian children with Hib infections other than epiglottitis were significantly more likely to lack the G2m(n) allotype than controls (P less than 0.05). G2m(n) negative Caucasian children less than or equal to 18 mo old have a 5.1-fold higher risk of nonepiglottitic Hib infections than G2m(n) positive children (P less than 0.01). We conclude that allotypic variants of the gamma-2 heavy chain genes, or genes in linkage equilibrium with them, exert a regulatory influence on the caucasian antibody response to a variety of immunologically distinct bacterial polysaccharide antigens. Young Caucasian children of the low responder phenotype, i.e., those lacking the G2m(n) allotype, are genetically predisposed to Hib and perhaps other bacterial infections.

Adult↗
PubMed1986

[Previous antibiotic treatment in meningococcal infections].

Seventy four cases of meningococcal infection were studied. They attended the "Valle del Nalón" Hospital in Asturias, from february 1979 until january 1985. Seven children died (9.4%). We divided them into two groups: A, without any previous antibiotic treatment when they arrived at the hospital (58 cases), and B, with previous antibiotic treatment (16 cases). All the children who died belonged to group A. Only 56.2% from group B had petechias, contrasting greatly with the 93.1% in group A. The most predominant meningococcus was from the serum group B. In the 22 cases of meningitis brainstem auditory evoked response was carried out to detect any hearing impairment. This was found in 21.7% of the cases.

Child↗
PubMed1997

Management of clusters of meningococcal disease. PHIS Meningococcus Working Group and Public Health Medicine Environmental Group.

Guidance on the management of clustered cases of meningococcal disease has been revised following a review of the clusters that occurred in England and Wales between 1 April 1995 and 31 March 1996. Public health action is indicated for confirmed and probable cases but not in response to possible cases. The importance of microbiological confirmation is re-emphasised. Intervention is recommended for defined target groups when two or more confirmed or probable cases occur in a preschool group or school within a four week period. We present a framework to assist in the management of clusters of invasive serogroup C infections in larger and less defined communities.

Cluster Analysis↗
PubMed2005

Differential cytokine genotype frequencies among Canadian Aboriginal and Caucasian populations.

Genetic diversity related to the human immune response is a key factor in individual and population survival throughout human history. Population diversity in disease susceptibility and resistance have been identified and linked to differences in cytokine mRNA and protein expression levels. Polymorphisms in the regulatory regions of cytokine genes can influence gene transcription levels and they have been associated with susceptibility to, and/or severity of, autoimmune disorders such as rheumatoid arthritis, meningococcus and sepsis. It is reported here that in two study populations, Canadian Aboriginal individuals have a higher frequency of cytokine single-nucleotide polymorphisms favouring a low production of TNFalpha, IFNgamma and IL-10 and high production of IL-6 as compared to a Caucasian population. We postulate that the evolution of this unique cytokine genotype profile may be linked to the Aboriginal adaptation to selection pressures related to an environment in which helminthic, parasitic and fungal infections predominated.

Cytokines↗