Bacterial meningitis in patients with sickle cell anemia in Salvador, Bahia, Brazil: a report on ten cases

ABSTRACT Sickle cell anemia (SCA) is a common genetic blood disorder, affecting millions worldwide. According to current evidence, individuals with SCA have more than 300 times greater risk to develop bacterial meningitis (BM) than the general population. Herein we have described the characteristics of a series of BM cases in SCA patients in Salvador, Brazil, during 13 years of hospital-based surveillance. Data on clinical presentation, laboratory parameters and outcomes were collected retrospectively by reviewing medical records. From 1999 to 2011, ten SCA patients were identified among the 2511 cases of BM (10/2511; 0.40%). These patients were more likely to be male (90%) and to be younger (median age 8.5 years). The causative agents were Streptococcus pneumoniae (n = 5) and Haemophilus influenzae (n = 1). The most frequent pneumococcal serotypes were 23 F (2 cases), 14, 18 F, 23B (one case each). Common medical complications were stroke (n = 3); heart failure (n = 2), respiratory problems (n = 2), renal dysfunctions (n = 2) and leg ulcers (n = 1). This study highlights the importance of S. pneumoniae as a causative agent of meningitis in individuals with SCA and shows the diversity of comorbidities associated with this condition.

Cambios en el Patrón Epidemiológico y resistencia Bacteriana de la Meningitis Bacteriana Aguda en Niños en un hospital de referencia

Introducción. Pos-introducción de la vacuna anti-H. influenzae tipo b (HIB) se ha observado en Latinoamérica significantes cambios en el perfil epidemiológico y de la susceptibilidad de los gérmenes causantes de meningitis bacteriana aguda. No se disponen de estudios similares en el Paraguay. Objetivo: Estudiar el panorama epidemiológico actual de la meningitis bacteriana aguda en el Paraguay, posterior a la introducción de la vacuna anti-HIB en el país, en un hospital de referencia. Materiales y métodos: Estudio observacional y retrospectivo en el que se incluyeron todos los casos de meningitis bacteriana aguda en niños 3 meses hospitalizados en el IMT desde enero de 1993 a junio del 2006. Se analizaron las fichas clínicas de los pacientes (pts) incluyendo datos demográficos, etiológicos y la evolución clínica. Los pts fueron estratificados según el año de hospitalización en tres periodos: Periodo I (PER I), que incluyó los que se hospitalizaron entre 1993 y 1997, PER II entre 1998 y 2002 y PER III del 2003 a 2006. Se determinó la CIM a penicilina (PEN) y cefotaxima (CFX) de los aislados de S. pneumoniae (Spn) por el método ipsilométrico (E-test) realizándose la serotipificación por la reacción de Quellung. Resultados: En el periodo de estudio se hospitalizaron 394 pts con meningitis bacteriana aguda. La edad media fue 2.9 + 4 años, con discreto predominio del sexo masculino (relación 1.2/1). La serotipificación realizada en 31 cepas de Spn (a partir del 2000) mostró que solo 50% de los serotipos correspondieron a los incluidos en la vacuna conjugada antineumocóccica actualmente disponible, siendo el 14 (9/31, 29%) el más frecuente. Conclusiones: La introducción de vacuna anti Hib ha producido un importante cambio epidemiológico de la meningitis bacteriana aguda en nuestra institución, constituyendo actualmente el S. pneumoniae el principal causante de meningitis bacteriana aguda. Se siguen observando, sin embargo, casos esporádicos de meningitis bacteriana aguda por HIB. Aunque se constata un significativo incremento de la resistencia de Spn a PEN, la resistencia a CTX se halla todavía <10%.

Abstract Introduction. Post-introduction of the anti-H. influenzae type b (HIB) vaccine has been observed in Latin America a significant changes in the epidemiological profile and susceptibility of germs that cause acute bacterial meningitis. No similar studies have in Paraguay. Aim: Study the current epidemiological situation of acute bacterial meningitis in a referral hospital after the introduction of Hib vaccine in Paraguay. Materials and methods: observational, retrospective study in which all cases of acute bacterial meningitis in children 3 months hospitalized in the IMT from January 1993 to June 2006 included the medical records of patients were analyzed (pts) including demographics, etiologic and clinical outcome. Pts were stratified by year of hospitalization in three periods: Period I (PER I), which included those who were hospitalized between 1993 and 1997, PER II between 1998 and 2002 and PER 2003 to 2006. III CIM was determined penicillin (PEN) and cefotaxime (CFX) isolates of S. pneumoniae (SPN) for the ipsilométrico method (E-test) carried out by the reaction serotyping Quellung. Results: During the study period 394 pts with acute bacterial meningitis were hospitalized. The mean age was 2.9 ± 4 years, with discreet predominance of males (ratio 1.2 / 1). Serotyping performed in 31 strains of Spn (since 2000) it showed that only 50% corresponded to serotypes included in the pneumococcal conjugate vaccine currently available, with 14 (9/31, 29%) the most frequent. Conclusions: The introduction of Hib vaccine has been a major epidemiological change of acute bacterial meningitis in our institution, now constituting the S. pneumoniae the leading cause of acute bacterial meningitis. Are still evident, however, sporadic cases of acute bacterial meningitis HIB. Although a significant increase in resistance of Spn PEN, CTX resistance is observed is still only <10%.

Detection of bacterial meningitis among children in Ulaanbaatar, Mongolia from 2002 to 2010 / Монголын Анагаах Ухаан

Background. Bacterial meningitis is a severe, potentially life-threatening infection that is associated with high rates of morbidity and significant disability in survivors. Overall mortality rates related to bacterial meningitis of around 20% to 25% have been reported by major centers. Our study is to determine the incidence rate and etiology of childhood bacterial meningitis in Ulaanbaatar, Mongolia.Methods. From 2002-2010, a total of CSF 433 and blood 544 samples were obtained from children age 0-5 years old. The following diagnostic criteria for bacterial meningitis in children aged 0-5 years were used: questionnaires, clinical signs and positive CSF culture and/or CSF antigen test results positive N. meningitis serogroups B, A, C, Y, and W-135, Hib or S.pneumonia; and/or positive CSF PCR results; and/or positive blood culture results with CSF pleocytosis (WBC count, >10 cells/uL). Pathogens were identified and serotype or serogroup with standard methods in the reference microbiology laboratory. Detection of bacterial pathogens with a multiplex and real-time PCR assay.Results. From totally 544 suspected cases had been detected bacterial meningitis in 260 (47, 8%) cases and sepsis in 111 [20,4%] cases respectively. The disease in the 83 [27.1 %] etiologically diagnosed patients was due to H.influenza, S. pneumonia was in 71 [36, 4%] cases and N.meningitis in 111 [24, 7%] respectively. Among the positive samples 80.6% (129/160) the specific serogroup and/or serotypes for N.meningitis serogroups A was available in 22(35, 4%) cases, for the Hib 52(96, 3%) and 6(40%) for the S.pneumoniae 7 serotype. The real time PCR assay was more sensitive for detection of meningitis pathogens than conventional methods (culture and latex agglutination), 19% in comparison with latex agglutination (p<0.0026) and by 39% in comparison with culture (p<0.001). Bacterial meningitis was identified 70.0 in 2004 among population, but it reduced until 5.0 in 2009. The incidence of Hib meningitis was 2002-2005y, N.meningitis and S.pneumoniae meningitis were 2006-2008y, S.pneumonia meningitis was more higher 2009-201 Oy comparing with other pathogens.Conclusion. N.meningitidls, S.pneumoniae H.influenzae type b are the leading causative agents of childhood bacterial meningitis in Ulaanbaatar, and the incidence rate is higher than what were reported in other Asian countries.

NTAGI subcommittee recommendations on haemophilus influenzae type b (Hib) vaccine introduction in India.

Background: WHO estimates that Haemophilus influenzae type b (Hib) caused over 8 million cases of serious disease and 376,000 deaths globally in the year 2000. The introduction of Hib vaccines has essentially eliminated Hib disease in countries where they are routinely used. Now, almost all Hib disease cases and deaths occur in countries where Hib vaccines is not incorporated in the routine immunization program. Process: The Hib and Pneumococcal subcommittee of National Technical Advisory Group on Immunization (NTAGI) in India met in April 2008. This paper focuses on the discussions regarding Hib vaccine introduction; the pneumococcal vaccine discussion is being published separately. The subcommittee reviewed the available published and unpublished literature as well as consulted prominent Hib experts to make an informed decision regarding the introduction of Hib vaccine into the routine Universal Immunization Program (UIP) in India. Objectives: The meeting was conducted with the objectives of reviewing the existing Indian, regional and global data on Hib disease (meningitis and pneumonia), the data on safety and immunogenecity of Hib vaccines manufactured in India, as well as the programmatic and operational requirements for the introduction of Hib vaccine in India, with the goal of making a recommendation on the introduction of Hib vaccine into the UIP. Recommendations: The committee noted that Hib diseases burden is suffiently high in India to warrant prevention by vaccination. Hib vaccines have been demonstrated to be safe, both globally and in India, and extremely efficacious in all settings where they have been used. Hib vaccine fits into the UIP immunization schedule. Several Indian manufacturers are currently producing Hib vaccines, and a detailed analysis showed that supplier capacity would be sufficient to meet the present and future demand for India if given sufficient lead time to increase production. Recognizing that it is the poorest children that are most at risk, the Indian Academy of Pediatrics has already recommended this vaccine for routine use in India. This subcommittee strongly recommended that Hib vaccine should immediately be introduced in India’s UIP.

Incidencia de meningitis y neumonías bacterianas agudas en menores de cinco años: Provincia del Guayas – Ecuador, años 2002 – 2005 / Incidence of meningitis or acute bacterial pneumonias in children less than 5 years old: Province of Guayas – Ecuador, year 2002-2005

Tipo de estudio: prospectivo, descriptivo, longitudinal. Objetivos: determinar la situación epidemiológica de meningitis y neumonías causadas por H. Influenzae tipo b (Hib) y documentar el impacto de la vacuna pentavalente en la incidencia de meningitis y neumonías causadas por Hib. Materiales y métodos: se incluyeron a los niños menores de 5 años que acudieron a la Emergencia del hospital del niño “Dr. Francisco de Ycaza Bustamante” con cuadro clínico sospechoso de meningitis y neumonías bacterianas agudas (MBA y NBA) entre los años 2002 – 2005, a quienes se le realizó punción lumbar con estudio citoquímico y cultivo de LCR; y rx standard de tórax con hemocultivo, respectivamente. Resultados: Se incluyeron 1355 pacientes (206 para meningitis bacteriana aguda y 1119 para neumonía bacteriana aguda) que cumplían con las definiciones de casos sospechosos; al final del período se confirmaron 47 casos de meningitis con aislamiento en laboratorio de haemophilus influenzae; y, de las 487 neumonías bacterianas confirmadas, se aisló en 12 de ellas, el Hib. Así mismo se observó la presencia importante del streptococo pneumoniae como agente causal de 9 casos de meningitis bacteriana y 21 casos de neumonías bacterianas agudas. Conclusiones: el impacto de la vacunación en la reducción de las patologías causadas por el Hib es evidente un año después, a partir del año 2004; así como la tendencia sostenida del streptococo pneumoniae como agente causal de MBA y NBA; la vacuna pentavalente no actúa sobre esta bacteria.

Type of Study: Prospective, descriptive and longitudinal. Objectives: Determine the epidemiology of meningitis and pneumonias caused by H. influenzae type B and Document the impact of immunization in the incindence of meningitis and neumonia caused by Hib. Material and method: Children less than 5 years old who went to the emergency department of “Dr. Francisco de Ycaza Bustamente” Children’s Hospital with a clinical history suspected to be meningitis or acute bacterial pneumonia between the years 2002-2005. This patient underwent lumbar tap for citochemical study and culture of the CSF, a chest x-ray and blood culture. Results: A total of 1355 patients were included in the study in which 206 were diagnosed with acute bacterial meningitis and 1119 with acute bacterial pneumonia. At the end of the study 47 cases of meningitis by H. influnenzae was confirmed and 487 bacterial pneumonias were confirmed only 12 were produced by Hib. Streptococcus pneumoniae was the microorganism for 9 of the cases of bacterial meningitis and for 21 of cases of bacteria pneumonia. Conclusions: The impact of immunization in lowering the incidence of these pathologies caused by HiB is evident a year later during year 2004.

Causative Organisms in Children with Bacterial Meningitis(1992-2002)

PURPOSE: This study was performed to assess the difference of organisms causing bacterial meningitis according to time. METHODS: We analyzed retrospectively 40 medical records of bacteriologically proven meningitis from 1992 to 2002. We divided them into two groups; neonate's group(14 cases), and children's group(26 cases). The results of the neonate's group were compared with those of previously reported articles in Korea, in 1970s-1980s. The causative agents of the children's group were analyzed according to the stage before and after the introduction of H. influenza type b(Hib) vaccine. RESULTS: In neonates, Group B streptococci(GBS) was the most common cause of bacterial meningitis. There was a trend in Korea that major causative agents of neonatal bacterial meningitis have changed from gram negative bacteria including E. coli to gram positive bacteria including GBS. In children, H. influenzae was isolated in six out of 11 cases(55%) in 1992-95, before the introduction of Hib vaccine, while two out of seven(29%) were isolated in 1999-2002, after the introduction of the Hib vaccine. CONCLUSION: Our study showed that the most common agent of neonatal bacterial meningitis was GBS. There was a trend that after the introduction of Hib vaccine, the incidence of H. influenza meningitis decreased in children.

H.influenzae and S.pneumoniae percentage in healthy children at ViXuyen (Ha Giang) and Van Don (Quang Ninh)

The study was performed on 496 healthy children under five year- old age living in Hagiang and Quangninh province to discover of carrying of H.influenzae and S.pneumoniae. The results showed that: The carries with H.influenzae in Vixuyen (Hagiang) were 24% and 14.7% in Vandon (Quangninh). Ones with S.pneumoniae were 10.7% in Vixuyen (Hagiang) and 15% in Vandon (Quangninh). Antibiotic resistance level of H.influenzae in Hagiang: co-trimoxarol 34.6%, chloramphenicol 23.1%, ampicillin 7.7%; in Vandon (Quangninh): co-trimoxarol 15%, chloramphenicol 12.8%, ampixiclin 7.5%..; no one of these strains resisted to cefuroxim axetil and norfloxacin. Antibiotic resistance level of S.pneumoniae in Vixuyen (Hagiang): co-trimoxarol 17.5%, chloramphenicol 12.5%, ampixiclin 7.7%.., no one of these strains resisted to benzyn-penixiclin; In Vandon (Quangninh): co-trimoxarol 17.5%, chloramphenicol 12.5%, no one of these strains resisted to benzyn-penixiclin.

Septic Hip in a Child due to H.influenzae: Problems with a Recent Experience / 대한정형외과학회잡지

We report a case of acute septic arthritis of the hip in a child due to H. influenzae with review of the problems encountered. A one year and 9 months-old male child was admitted because of fever, limping and restlessness of 48-hour duration. Under the impression of septic arthritis of the right hip, blind broad-spectrum antibiotic regimen was initially instituted. Fever subsided immediately and two blood cultures yielded no growth, as did joint tapping. But fever recurred on the 8th day of admission. MRI demonstrated fluid collection in the right hip. Arthrotomy yielded thin pus. The antibiotic regimen was shifted to vancomycin, according to the culture report of S. aureus. However, spiking fever continued. On the 4th week of admission, recheck MRI demonstrated fluid collection in and out of the hip joint. A second arthrotomy yielded frank pus. H. influenzae was reported in pus culture for the first time, being susceptive only to chloramphenicol. Fever was down to normal temperature after injection of urfamycin. Radiograph on the 17th day after the 2nd arthrotomy revealed posterior dislocation of the right hip. MRI demonstrated granulation tissue within the acetabulum. Open reduction confirmed granulation tissue without pus. This case suggests: 1. Routine blind antibiotic regimen for gram-positive and negative organisms in the initial phase of treatment may fail in the rare case of H. influenzae. This may lead the surgeon to miss the optimum time of surgical intervention despite early diagnosis, 2. Arthrotomy may fail if not followed by antibiotics sensitive to the pathogen. 3. Delayed pathologic dislocation may ensue due to invasion of granulation tissue.

Effect of Meconium Components on Haemophilus influenzae Growth by Surfactant

PURPOSE: Meconium is a complex mixture with a potential variable composition, it is difficulty to determine which components of meconium are responsible for the surfactant inhibition. We previous reported that Surfactant-TA and Exosurf almost completely inhibited the growth of Haemophilus influenzae at the concentration of 100% without apparent difference in the efficiency. In this study, We have determined the effect of Surfactant-TA on H. influenzae growth by meconium and futher investigated if this effect is caused by methanol or chloroform soluble meconium component. METHODS: Approximately 20gm of meconium was collected from 5 healthy full term newborn infants. That was suspended in distilled water at a concentration of 25mg/ml and filtered by Whatmann filter paper No.3. The filtrate was pooled, lyophilized and stored at-15degrees C. Filtered meconium was extracted with chloroform-methanol (2:1,v/v). Exponential growing H. Influenzae (2.7x 107cells in 0.1ml of PBS) were mixed with 0.2ml of Surfactant-TA (30mg/ml) at serial dilutions ranging from 0.1% to 100%. Mixed solution of bacteria, Surfactant-TA, and meconium (0.1ml) or it's subfractions were incubated at 37degrees C for 90 min. After incubation, the mixtures was serially diluted with PBS. Each diluted mixture were cultivated on chocolate agar plate. Volumes of inoculation were 0.1ml of mixture. Number of viable bacteria were estimated by colony counting after 18hours culture. For transmission electronmicroscopic finding, mixture of bacteria 100% surfactant-TA were proceeded to prepare. RESULTS: 1) Surfactant-TA almost completely inhibited the growth of H. influenzae at the concentration of 100%. 2) The meconium, methanol and chloroform meconium all did not affected the H. influenzae growth inhibition effect of Surfactant-TA. 3) Surfactant destroyed H. influenzae with disruption of cell membranes and leakage of intracellular organelles. CONCLUSIONS: The meconium and it's subfraction all did not affected the H. influenzae growth inhibition effect of Surfactant-TA. So, We speculated that using Surfactant-TA in meconium aspiration pneumonia will be beneficial to reducing severity of respiratory symptom. But more extensive controlled in vivo test need before surfactant therapy can be considered as a treatment modality for like this condition.