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The molecular epidemiology of Streptococcus pneumoniae isolates from carriage and cerebrospinal fluid (CSF) concurrently recovered from the same individual has not yet been reported. By using pulsed-field gel electrophoresis, we demonstrated the genetic linkage among strains from CSF and nasopharynges of two children with pneumococcal meningitis. CASE REPORTS Case 1. A boy 4 years and 10 months old was admitted to the Tropical Diseases Hospital in Goiânia, Brazil, in July 2000 with a 2-day history of prostration, vomiting, and fever. The child had been well until 7 days earlier, when he developed flu-like symptoms and acute otitis media. No antimicrobial therapy had been administered before admission. The patient had never received any kind of bacterial meningitis vaccine and was not attending any day-care center. On examination, he was lethargic and presented signs of meningeal irritation. The axillary temperature was 38.5°C, and the pulse was 78 beats/min. A lumbar puncture disclosed cloudy cerebrospinal fluid (CSF), and laboratorial analysis revealed a white cell count of 390 cells/ml (85% polymorphonuclear cells), a protein level of 116 mg/dl, and a glucose level of 2.5 mg/dl. Gram staining of the CSF showed gram-positive cocci in pairs and chains. The child was treated with ceftriaxone (1.5 g/day intravenously). Culturing of CSF and blood was carried out according to standard procedures (11) and World Health Organization guidelines (18) and yielded Streptococcus pneumoniae susceptible to penicillin and also to other antimicrobial agents (Table 1). The child completed a 12-day course of treatment with ceftriaxone and was discharged from the hospital in good health.Case 2. A 4-month-old boy was admitted to the same hospital in August 2000. He had been well until 1 week before admission, when he developed flu-like symptoms and subsequent yellow nasal discharge. He received erythromycin for 3 days. One day before admission, he presented with fever, vomiting, and irritability. On examination, the axillary temperature was 37.6°C, the pulse was 120 beats/min, and he had a stiff neck and a bulging fontanelle. The child did not attend any day-care center. He had received one dose of Haemophilus influenzae type b (Hib) vaccine, but no pneumococcal vaccine had been administered. A lumbar puncture yielded cloudy CSF, and laboratorial analysis revealed a white cell count of 2,340 cells/ml (98% polymorphonuclear cells), a protein level of 110 mg/dl, and a glucose level of 2.5 mg/dl. Gram staining of the CSF showed gram-positive cocci in pairs and chains. In accordance with a local protocol, treatment with ampicillin and chloramphenicol was then initiated. In our institution, this drug combination is an alternative to ceftriaxone and has also been employed in empirical therapy of bacterial meningitis in children, pending CSF and blood culture results. Since the child did not show clinical improvement, the drugs used for antimicrobial therapy had to be switched to ceftriaxone. Culture of CSF yielded S. pneumoniae, and no p...

Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis being the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib), and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect) and of their carriage status (indirect effect). We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

We present a case of invasive pneumococcal infection in a healthy 10-month-old infant from whom Streptococcus pneumoniae serotype 23F was isolated from the blood and serotype 23B was isolated from the cerebrospinal fluid. Both serotypes were penicillin nonsusceptible. Pulsed-field gel electrophoresis analysis demonstrated that the two serotypes had distinct DNA patterns, indicating that infection did not occur as a result of capsular transformation but as a result of a mixed infection with two distinct pneumococcal serotypes. CASE REPORTIn July 2001, a previously healthy 10-month-old boy was admitted to the Tropical Diseases Hospital in Goiânia, Central Brazil, with a 2-day history of fever, irritability, and vomiting. There was no history of otitis media, pulmonary infection, or immunosuppressive illness. He had received two doses of an oral antimicrobial 12 h before admission, but his parents did not know its name. He had previously received three doses of Haemophilus influenzae type b conjugate vaccine, but he had not been vaccinated against Streptococcus pneumoniae. On admission, he was afebrile. He had meningeal signs and a bulging fontanelle, but the rest of the physical exam was unremarkable. Blood cultures were obtained and a lumbar puncture was performed immediately. The cerebrospinal fluid (CSF) was cloudy, with a white cell count of 6,750 cells/ml (90% polymorphonuclear cells), a protein level of 85 mg/dl, and a glucose level of 63 mg/dl. A Gram stain of the CSF was negative. A complete blood count showed 26,500 leukocytes/mm 3 (14% bands, 56% neutrophils, 26% lymphocytes, and 4% monocytes). The hemoglobin was 9.4 g/dl, the hematocrit was 28.3%, and the platelet count was 274,000/mm 3 . Treatment was begun with ceftriaxone (100 mg/kg of body weight/day) and dexamethasone, and after a 10-day course of treatment, the patient was discharged in good health.Cultures of the patient's blood and CSF grew S. pneumoniae. According to NCCLS standards (9), both isolates were nonsusceptible to penicillin (MIC ϭ 0.125 g/ml) and trimethoprim-sulfamethoxazole (MIC ϭ 4.0 g/ml) and susceptible to chloramphenicol (MIC ϭ 1.0 g/ml for blood and 2.0 g/ml for CSF), ceftriaxone (MIC ϭ 0.06 g/ml), vancomycin (MIC ϭ 0.5 g/ml), and erythromycin (MIC ϭ 0.03 g/ml). Both isolates were serotyped by the Quellung reaction with sera produced by the Statens Seruminstitute, Copenhagen, Denmark. The tests were performed at the Adolfo Lutz Institute, the national reference center for S. pneumoniae located in São Paulo, Brazil. Serotype 23F was identified in the blood, and serotype 23B was identified in the CSF. These results were confirmed by the National Center for Streptococcus in Edmonton, Canada.The genetic relatedness of the two pneumococcal isolates was investigated at the Adolfo Lutz Institute by pulsed-field gel electrophoresis (PFGE) of chromosomal DNA after SmaI digestion, as previously described (8). As shown in Fig. 1, the two isolates presented different DNA restriction patterns (lanes A and B) with seven band differences acc...

ObjectiveTo assess the impact of the Haemophilus influenzae b (Hib) conjugate vaccine in reducing the incidence of meningitis among children under five years old. Methods A 'before-after' design was used to compare Hib meningitis incidence rates in the pre-vaccine (July 1995 -June 1999) and post-vaccine (July 1999 -June 2001 periods in the state of Goiás, central Brazil . Bacterial meningitis case definition was based on World Health Organization criteria. Incidence rates of S. pneumoniae and N. meningitidis were used for comparison purposes. Chi-squared and Student's t tests were used for statistical analysis. P-values below 0.05 were considered as statistically significant. Results 979 children with acute bacterial meningitis were detected throughout the entire period. The incidence rate of Hib meningitis decreased from 10.8 (x10 5 ) in the pre-vaccine period to 2.3 (x10 5 ) in the 2 nd year post vaccination, leading to a risk reduction of 78%, targeted to the 7-23 months age group (p<0.05). A total of 65 cases of Hib meningitis were prevented. An increase in S. pneumoniae meningitis was observed. Vaccine failure was detected in one child. Conclusions This study showed that mass immunization with Hib conjugate vaccine brought about an expressive decline in childhood Hib meningitis in Goiás soon after the first year. Notwithstanding, an enhancement of surveillance using high-accuracy tools is essential to: (i) detect a possible reemergence of Hib; (ii) identify vaccine failure, and (iii) monitor changes in the H. influenzae serotype profile over time.