Haemophilus Influenzae Meningitis Research Articles

Efficacy and Prolonged Safety of Haemophilus influenzae Type b Conjugate Vaccines.

The purpose of this study was to find data proving the influence of the Haemophilus influenzae type b (Hib) conjugate vaccination on the frequency of invasive Hib illness. A systematic literature search was conducted on the PubMed database to identify peerreviewed publications pertaining to the epidemiology of Haemophilus influenzae meningitis, both before and after the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines. The search query employed a combination of relevant keywords, including "invasive," "Haemophilus," "influenzae," "meningitis," and specific serotype b (Hib). Additionally, terms related to epidemiology, burden, risk factors, impact, Hib vaccine, Hib conjugate vaccine, combination vaccine, vaccine production, efficacy, immunisation coverage, surveillance, review, clinical aspects, outcomes, and various age groups (adults and children) were incorporated. The search encompassed articles published till now. Subsequently, relevant research papers concerning Haemophilus influenzae meningitis were subjected to a comprehensive review and analysis. The Hib conjugate vaccination has shown to be extremely effective when administered to the entire population. However, changes to the immunisation protocol appear to be required in order to effectively manage invasive Hib illness.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and tetralogy of fallot; Case report and literature review

WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome is a rare primary immunodeficiency disorder characterized by susceptibility to human papillomavirus (HPV) infections, neutropenia, and hypogammaglobulinemia. WHIM syndrome is caused by a gain-of-function mutation CXCR4, leading to increased responsiveness of neutrophils and lymphocytes to CXCL12. This results in an accumulation of atypical hypersegmented mature neutrophils in the bone marrow and peripheral blood neutropenia. This case report discusses a 10-year-old girl who was diagnosed with WHIM syndrome at the age of four years following Haemophilus influenzae meningitis. She was found to have Tetralogy of Fallot at birth, which was surgically repaired when she was one year old. She was also found to have significant neutropenia during surgery and received multiple doses of G-CSF with a good response. She presented to the hospital at the age of four years with fever, neck stiffness, lethargy, and headache and was diagnosed with H. influenzae meningitis. Her immunology workup revealed significant neutropenia and hypogammaglobulinemia, as well as low antibody levels to H. influenza type B, tetanus toxoid, and Streptococcus pneumonia, despite up-to-date vaccination. Furthermore, decreased levels of T cells and B cells were detected. The patient was started on IgG replacement therapy and Bactrim prophylaxis. Bone marrow biopsy revealed granulocytic hyperplasia and occasional hypersegmented neutrophils, suggesting myelokathexis. Genetic testing revealed a heterozygous CXCR4 mutation with a premature stop codon (p.Ser338Ter), confirming the diagnosis of WHIM syndrome. This case report highlights the association of WHIM syndrome with congenital heart defects, such as Tetralogy of Fallot. A literature review revealed three other cases of congenital heart defects in patients with WHIM syndrome, indicating a potential role for CXCR4 and CXCL12 in septum formation. The rarity of the disorder and the lack of a universal screening tool makes the diagnosis of WHIM syndrome difficult. Therefore, physicians should consider WHIM syndrome in patients with congenital heart defects, particularly if they have recurrent HPV infections, neutropenia, and hypogammaglobulinemia.

Serum immunoglobulin levels in children with acute bacterialmeningitis

To assess serum level of immunoglobulins (IgG, IgA, IgM) in children with acute bacterial meningitis before therapy and at the end of intensive antibiotic therapy and in COMparison 1 heallity age aiid scx mittchicd vonirsls. Out of 37 vases adinived ta Thi-Als Atheer pediatric hospital (Mosul city) between January 2005 and July 2007, 29 cases proved to be a case of Haemophilus influenzae meningitis. Two died during the follow up period and 27 completed the study. Also included 30 apparently healthy age and sex matched subjects taken as control group. Initially from both group (patients and control) Sml venous blood samples were taken and assay of serum immunoglobulin (IgG, IgA, IgM) were done by single radial immunodiffusion method using commercial kits. After two weeks of intensive antibiotic therapy another blood samples were taken from the patients and assay of serum immunoglobulin levels were done using the same method and the same commercial kits. Initially before therapy there was a significant reduction in all immunoglobulin levels (IgG, IgA, IgM) in children with acute bacterial meningitis in comparison to controls. After 2 weeks of intensive antibiotic therapy, there was no significant difference in the mean serum immunoglobulin levels between the patients and controls. Acute bacterial meningitis as a disease and the intensive antibiotic therapy do affect the humoral immune response as reflected by the serum immunoglobulin levels (IgG, IgA, IgM).

Vaccine Decision-making in a Time of Conflicting Recommendations: A Call to Go Beyond Politics.

Vaccine Decision-making in a Time of Conflicting Recommendations: A Call to Go Beyond Politics.

A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami.

Alazami syndrome is a rare autosomal recessive neurodevelopmental disorder due to loss-of-function variants in the La ribonucleoprotein 7 (LARP7) gene. Children with Alazami syndrome are most often affected by a combination of primordial dwarfism, intellectual disability, and distinctive facial features. Previous cases have been primarily found in consanguineous families from the Middle East, Asia, and North Africa. We present a 21-month-old Caucasian male from the Midwest United States with nonconsanguineous parents who presented with frequently reported findings of unusual facial features, poor growth, cardiac and genitourinary findings, and developmental delay; less-frequently reported findings, including transient erythroblastopenia of childhood (TEC) and immune deficiency; and never-before reported findings of periventricular nodular heterotopia and stroke. He developed stroke during a hospitalization for Hemophilus influenzae meningitis. The possible contributions of LARP7 to TEC, immune deficiency, brain malformation, and stroke are discussed. Guidelines for the care of Alazami patients are proposed.

An Outlook on Breastfeeding Assessment Tools- A Review

Breastfeeding is a biological inheritance shared by women all around the world. It is the ‘natural’ way to feed new born babies, and the best source of nutrition for infants. After birth, loose stools and pneumonia are more frequent and serious in the formula fed babies, and can cause deaths. Otitis media, haemophilus influenza meningitis, and urinary tract infection are less frequent in babies who are fed human milk. Infants who are formula fed have a greater chance of developing chronic illnesses, such as asthma, diabetes mellitus type l, and intestinal diseases like inflammatory bowel disease. Coordination of mother and infant is most important for breast feeding to be successful. Ineffective breast feeding can contribute to mortality among new born babies and infants. Hence various breastfeeding assessment tools have been developed to advise and promote mother’s comfort, motivation, and assess the infant's neurobehavioural development. In this review, the literature to find out the most commonly used breastfeeding assessment tools, their salient features, advantages and disadvantages, acceptability, usage and validation have been reviewed.

COVID-19: Cross Reactive Immunity, Herd Immunity, and Convalescent Serum Therapy

Objective: To present various types of vaccines and viral infections which can induce cross-reactive immunity against COVID-19. In addition, this article discusses the role of herd immunity and convalescent serum therapy in preventing and controlling SARS CoV-2. The study also determined the claims and counterclaims about their protective and therapeutic effects.
 Method: Non-systematic review was done using different articles done on cross-reactive immunity against COVID-19 through vaccinations, previous infections, herd immunity and the therapeutic effects of convalescence serum. The search was done on the PubMed, Google Scholar, and Science Direct, WHO, Euro-surveillance, CDC databases. 
 Results: Many observational correlational studies reported that BCG decreases the incidence and mortality from COVID-19. Furthermore, homology between the COVID-19 virus and the measles, mumps, and rubella (MMR) viruses was discovered. Few studies suggested the presence of cross-immunity between MMR vaccine and SARS-CoV-2. Similarly, few studies suggested protective effects of Oral Polio Vaccine (OPV) against SARS-CoV-2; since both viruses are positive-single-strand RNA (+ssRNA). Diphtheria, pertussis, and tetanus (DPT) vaccines, particularly those that include inactivated whole pertussis vaccine, might induce B and T cell cross-reactive immunity against SARS-CoV-2. Other vaccines against Streptococcus pneumonia, Haemophilus influenza, and Meningococcal meningitis vaccines are suggested also to induce some immunity against Covid-19. It is hypothesized that infections with other Coronaviruses may cause protection against SARS-CoV-2. However, the studies done on these suggestions were mostly observational that can carry a high chance of inherent biases. There are also claims and counterclaims about the effect of herd immunity and convalescence serum on the prevention and control of Covid-19. So, appropriately designed RCTs are needed to prove or disprove their protective and therapeutic effects.
 Conclusions: There are claims and counterclaims about the protective effects of different vaccines, previous infections, and herd immunity and regarding the therapeutic effects of convalescence serum. Comparing with other vaccines, BCG was suggested to have the highest cross-reactive epitopes against SARS-Cov-2 virus. MMR, OPV, DPT, Influenza, Pneumococcal and meningococcal vaccines are suggested to protect against Covid-19. Previous infection with other Corona viruses, herd immunity and convalescence serum may play roles in the prevention and control of Covid-19. Many large clinical trials are undergoing nowadays and their results are needed to prove or disprove the cross-immunity related to SARS-CoV-2 and the effect of convalescence serum.

Haemophilus influenzae Meningitis Direct Diagnosis by Metagenomic Next-Generation Sequencing: A Case Report.

Current routine real-time PCR methods used for the point-of-care diagnosis of infectious meningitis do not allow for one-shot genotyping of the pathogen, as in the case of deadly Haemophilus influenzae meningitis. Real-time PCR diagnosed H. influenzae meningitis in a 22-year-old male patient, during his hospitalisation following a more than six-metre fall. Using an Oxford Nanopore Technologies real-time sequencing run in parallel to real-time PCR, we detected the H. influenzae genome directly from the cerebrospinal fluid sample in six hours. Furthermore, BLAST analysis of the sequence encoding for a partial DUF417 domain-containing protein diagnosed a non-b serotype, non-typeable H. influenzae belonging to lineage H. influenzae 22.1-21. The Oxford Nanopore metagenomic next-generation sequencing approach could be considered for the point-of-care diagnosis of infectious meningitis, by direct identification of pathogenic genomes and their genotypes/serotypes.

Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children.

Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs TLR4 rs4986790 (896A > G) and TLR9 rs187084 (−1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in TLR4 was significantly higher in patients with Haemophilus influenzae meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–5.4; p = 0.021), whereas the frequency of variant genotypes in TLR9 was significantly lower in patients with H. influenzae meningitis than controls (OR, 0.4; 95% CI, 0.2–0.9; p = 0.036). No such differences were found with other causative pathogens, such as Streptococcus pneumoniae and Neisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant TLR4 genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52–109.80; p = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07–131.49; p = 0.044) than those with the wild-type TLR4 genotype. Our study suggests an association between H. influenzae meningitis and genetic variation between TLR4 and TLR9 in Angolan children.

Two cases of type-a Haemophilus influenzae meningitis within the same week in the same hospital are phylogenetically unrelated but recently exchanged capsule genes

Haemophilus influenzae causes common and sometimes severe adult and pediatric disease including chronic obstructive respiratory disease, otitis media and infections of the central nervous system. Serotype b strains, with a b-type capsule, have been the historical cause of invasive disease, and the introduction of a serotype b-specific vaccine has led to their decline. However, unencapsulated or non-b-type H. influenzae infections are not prevented by the vaccine and appear to be increasing in frequency. Here we report two pediatric cases of severe central nervous system H. influenzae infection presenting to the same hospital in San Diego, California during the same week in January 2016. Due to good vaccine coverage in this part of the world, H. influenzae cases are normally rare and seeing two cases in the same week was unexpected. We thus suspected a recent transmission chain, and possible local outbreak. To test this hypothesis, we isolated and sequenced whole genomes from each patient and placed them in a phylogenetic tree spanning the known diversity of H. influenzae . Surprisingly, we found that the two isolates (SD2016_1 and SD2016_2) belonged to distantly related lineages, suggesting two independent transmission events and ruling out a local outbreak. Despite being distantly related, the two isolates belong to two different lineages that have exchanged capsule loci in the recent past. Therefore, as in other bacterial pathogens, capsule switching by horizontal gene transfer may be an important evolutionary mechanism of vaccine evasion in H. influenzae .

Clinical characteristics of 84 children with invasive Haemophilus influenzae infection from 2014 to 2018

Objective: To investigate the clinical characteristics of invasive Haemophilus influenzae (HI) infection in children. Methods: The clinical manifestations, laboratory examinations and treatment outcomes of 84 children with HI infection confirmed by bacterial culture in 7 tertiary children's hospitals from 2014 to 2018 were analyzed retrospectively. Results: Among the 84 cases, 50 were males. The age was 1.54 years (ranged from 5 days to 13 years).Twenty cases (24%) had underlying diseases and 48 cases (57%) had not received antibiotics before collecting specimens. Eighty-two cases (98%) had fever and 75 cases (89%) had clear infection foci, among which 31 cases (37%) had meningitis and 27 cases (32%) had pneumonia. Blood culture was positive in 62 cases (74%), cerebrospinal fluid culture was positive in 10 cases (12%), blood culture and cerebrospinal fluid culture were both positive in 11 cases (13%). Antibiotics susceptibility test showed that 27% (22/82) of all HI strains produced β-lactamases and 48% (37/77) strains were resistant to ampicillin. The drug resistance rates to cefuroxime, ampicillin-sulbactam, trimethoprim-sulfamethoxazole and azithromycin were 25% (20/80) , 20% (9/45) , 71% (44/62) and 19%(11/58), respectively. All strains were sensitive to meropenem, levofloxacin and ceftriaxone. After sensitive antibiotic therapy, 83% (70/84) of all patients were cured and improved, the mortality rate and loss of follow-up rate were 13% (11/84) and 4% (3/84) respectively. Conclusions: Meningitis and pneumonia are common presentation of invasive HI infections in children. Mortality in HI meningitis children is high and the third generation of cephalosporins, such as ceftriaxone can be used as the first choice for the treatment of invasive HI infection.

Real-time PCR for the diagnosis of invasive Haemophilus influenzae bacteraemia and meningitis in children: A diagnostic accuracy study of over 2,000 samples

results in a paediatric patient cohort and to review discordant results. Methods: A retrospective audit of all blood and CSF samples from a tertiary referral paediatric hospital sent to the Irish Meningitis and Sepsis Reference Laboratory over a four-year period. All PCR tests performed for H. influenzae which had a contemporaneous culture performed were included in the analysis. Results: For the blood PCR test, there were 10 positive samples out of 1,367 samples tested. The sensitivity was shown to be 60% (95% CI 14.6–94.73%) and the specificity was 99% (95% CI 98–99.7%). For the CSF assay, the sensitivity was 100% (95% CI 15.8–100%) with a specificity of 99% (95% CI 99.2–99.9%) and there were 5 positive samples by PCR out of the 1,224 samples tested. Ten patients had positive PCR results, with a negative corresponding culture (blood=7, CSF=3). Three of the 10 cases were deemed to be primary H. influenzae infections, while seven were deemed to be likely co-infection (respiratory syncytial virus=2, Influenza=2, measles=1, rotavirus=1, Staphylococcus aureus pneumonia=1). Conclusions: The incidence of invasive H. influenzae disease was low in this population. The sensitivity and specificity of the assay in CSF was excellent, but the sensitivity of the assay in blood was lower at 60%. Most patients with discordant PCR/culture results had viral co-infections. A more rational approach to requesting PCR is required in paediatric patients.

Bacterial hypervirulence in haemophilus influenzae meningitis identified by whole genome sequencing

Haemophilus influenzae is a commensal of the human nasopharynx but can cause invasive disease including meningitis.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection

ObjectivesScreening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. MethodsEligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. ResultsThe study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. ConclusionPID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial

Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya. We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)-Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0·5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks-4 months, 5-17 months), and by baseline CD4% (<10, 10-14, 15-19, and ≥20). Data were obtained in an observer-blind manner, and the vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01148459. Between July 30, 2010, and May 24, 2013, we enrolled 200 children to our study and randomly assigned 99 to receive RTS,S/AS01 and 101 to receive rabies vaccine. 177 (89%) of the 200 children enrolled completed 14 months of follow-up. Serious adverse events were noted in 41 (41·4%, 95% CI 31·6-51·8) of 99 RTS,S/AS01 recipients and 37 (36·6%, 27·3-46·8) of 101 rabies-vaccine recipients (relative risk 1·1, 95% CI 0·8-1·6). 20 (20·2%, 95% CI 12·8-29·5) of 99 RTS,S/AS01 recipients and 12 (11·9%, 6·3-19·8) of 101 rabies-vaccine recipients had at least one serious adverse event within 30 days after vaccination, mainly pneumonia, febrile convulsions, and salmonella sepsis. Five (5·1%, 95% CI 1·7-11·4) of 99 RTS,S/AS01 recipients and four (4·0%, 1·1-9·8) of 101 rabies-vaccine recipients died, but no deaths were deemed related to vaccination. Mortality was associated with five cases of pneumonia (1% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), five cases of gastroenteritis (3% RTS,S/AS01 recipients vs 2% rabies-vaccine recipients), five cases of malnutrition (2% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), one case of sepsis (1% rabies-vaccine recipients), one case of Haemophilus influenza meningitis (1% rabies-vaccine recipients), and one case of tuberculosis (1% RTS,S/AS01 recipients). RTS, S/AS01 was well tolerated when given to children with WHO clinical stage 1 or 2 HIV disease along with high antiretroviral and co-trimoxazole use. Children with HIV disease could be included in future RTS,S/AS01 vaccination programmes. GlaxoSmithKline Biologicals SA and PATH Malaria Vaccine Initiative.

Clinical findings and management of patients with meningitis with an emphasis on Haemophilus influenzae meningitis in rural Tanzania

IntroductionThe spectrum of meningitis pathogens differs depending on the age of patients and the geographic region, amongst other. Although meningitis vaccination programs have led to the reduction of incidence rates, an imbalance between low- and high-income countries still exists. MethodsIn a hospital-based study in rural northern Tanzania, we consecutively recruited patients with confirmed meningitis and described their clinical and laboratory characteristics. ResultsA total of 136 patients with meningitis were included. Fever (85%), meningism (63%) and impairment of consciousness (33%) were the most frequent clinical symptoms/signs. Nearly 10% of all patients tested were positive for malaria. The majority of the patients with bacterial meningitis (39%), especially those under 5years of age, were confirmed to be infected with Haemophilus influenzae (26%), Streptococcus pneumoniae (19%) and Neisseria meningitidis (15%). Haemophilus influenzae represented the dominant causative organism in children under 2years of age. ConclusionOur study emphasizes the importance of recognizing warning symptoms like fever, meningism and impairment of consciousness, implementing laboratory tests to determine responsible pathogens and evaluating differential diagnoses in patients with meningitis in sub-Saharan Africa. It also shows that Haemophilus influenza meningitis is still an important cause for meningitis in the young, most probabaly due to lack of appropriate vaccination coverage.

Recurrent meningitis due to anatomical defects: The bacteria indicates its origin

Introduction: Recurrent meningitis is a rare disease. Anatomical abnormalities and immunodeficiency states are predisposing factors. Four cases, in which immunodeficiency was excluded, are presented. The causal microorganism led to the detection of the anatomical defect responsible for the recurrences. Patients and methods: Retrospective review of 4 cases with clinical diagnosis of recurrent bacterial meningitis. Results: Case 1: a thirty-month-old boy, with unilateral hearing loss, was diagnosed with Mondini abnormality by magnetic resonance imaging (MRI) after 2 episodes of Haemophilus influenzae meningitis. Surgical repair was after third recurrence. Case 2: a fourteen-year-old girl was diagnosed by MRI with cribriform plate defect after 3 episodes of meningitis due to Streptococcus pneumoniae. Ventriculoperitoneal shunt was placed. Case 3: a girl with meningitis due to Staphylococcus aureus at 2 and 7 months. MRI shows occipital dermal sinus requiring excision. Complication with cerebellar abscesses because of a coexisting dermoid cyst. Case 4: a child with meningitis due to Streptococcus bovis at 9 days and Enterococcus faecium, Klebsiella pneumoniae and Escherichia coli at 7 months, with positive cultures to Citrobacter freundii and

Meningitis recurrente por defectos anatómicos: la bacteria indica su origen

IntroductionRecurrent meningitis is a rare disease. Anatomical abnormalities and immunodeficiency states are predisposing factors. Four cases, in which immunodeficiency was excluded, are presented. The causal microorganism led to the detection of the anatomical defect responsible for the recurrences. Patients and methodsRetrospective review of 4 cases with clinical diagnosis of recurrent bacterial meningitis. ResultsCase 1: a thirty month-old boy with unilateral hearing loss, diagnosed with Mondini abnormality by magnetic resonance imaging (MRI) after 2 episodes of Haemophilus influenzae meningitis. Surgical repair after third recurrence. Case 2: fourteen year-old girl diagnosed by MRI with cribriform plate defect after 3 episodes of meningitis due to Streptococcus pneumoniae. Ventriculoperitoneal shunt was placed. Case 3: girl with meningitis due to Staphylococcus aureus at 2 and 7 months. MRI shows occipital dermal sinus requiring excision. Complication with cerebellar abscesses because of a coexisting dermoid cyst. Case 4: child with meningitis due to Streptococcus bovis at 9 days and Enterococcus faecium, Klebsiella pneumoniae and Escherichia coli at 7 months, with positive cultures to Citrobacter freundii and E. faecium later on. Spinal MRI led to the diagnosis of Currarino syndrome with CSF fistula, which was surgically repaired. The 4 patients had undergone image studies reported as normal during the first episodes. ConclusionsIn patients with recurrent meningitis the possibility of an anatomical defect should be considered. The isolated microorganism should help to locate it. It is essential to know the normal flora of the different anatomical sites. The definitive treatment is usually surgical.

Factors Affecting Time to Death From Start of Treatment Among Children Succumbing to Bacterial Meningitis

Many risks of death in childhood bacterial meningitis are well-identified, but factors influencing survival time have received less attention. Better understanding of this issue could help explain why adjuvant medications have performed unevenly in different trials. In a post hoc analysis of prospectively collected data from a large bacterial meningitis treatment trial in Luanda, Angola, we compared time to death after initiation of antimicrobial treatment among 206 children with etiology and other patient characteristics. The risks of dying very quickly (0-4 hours), quickly (4-8 hours) or after longer periods were analyzed by logistic regression. Median time to death was 18.5 hours, half the time in Streptococcus pneumoniae (11.8 hours) compared with Haemophilus influenzae (26.8 hours) meningitis. Of all deaths caused by pneumococcal or H.influenzae meningitis, 42% versus 16%, respectively, occurred within the first 8 hours. In addition, patients who succumbed within 8 hours, unlike those dying later, had a short disease history, shock, hypoglycemia and poor cerebrospinal fluid white cell response. Time to death in Angola is so short that hardly anything, except perhaps modern intensive care, is likely to improve outcome in a patient with meningitis, especially the pneumococcal disease.

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.