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PubMed2006

Comparison of mucosal and parenteral immunisation in two animal models of pneumococcal infection: otitis media and acute pneumonia.

Bacterial clearance and immune responses in a mouse model of pneumonia and a rat model of otitis media following parenteral or mucosal immunisation in both models were compared. Both the immunisation routes were equally effective in inducing bacterial clearance from the lung, upregulated the recruitment of white cells and lead to an increase in the concentration of TNF-alpha, IL-1beta and specific antibody in the bronchoalveolar lavage. Both the routes of immunisation enhanced clearance of bacteria from the middle ear. Parenteral immunisation was most effective overall in enhancing bacterial clearance and recruiting white cells to the middle ear. Both the routes significantly suppressed the levels of TNF-alpha in the middle ear lavage. Mucosal immunisation induced a Streptococcus pneumoniae-specific IgA antibody response. Both the animal models gave highly reproducible disease and provided high levels of sensitivity for testing the efficacy of candidate vaccine antigens. Differences observed in the inflammatory responses require further study.

Animals↗
PubMed2002

Invasive pneumococcal infections in children with asplenia.

BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. OBJECTIVE: To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. METHODS: Children with S. pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2,581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.

Child↗
PubMed1983

Severe pneumococcal infection in patients with neoplastic disease.

A study of pneumococcal bacteremia in 56 patients with neoplastic disease from January 1, 1972 to June 30, 1980 is presented and compared to an earlier study between 1955 and 1971. Patients at highest risk were those with Hodgkin's disease who had been splenectomized, multiple myeloma and chronic lymphocytic leukemia showing an attack rate of 15.6/1000, 12.5/1000, and 10.8/1000, respectively. The attack rate was more than three times higher among patients with Hodgkin's disease in the present series compared to the previous series. In 32% of cases there was no identifiable source for the infection. Four splenectomized patients with Hodgkin's disease developed pneumococcal meningitis and two died. The overall mortality rate was 32% versus a rate of 18% for those treated with appropriate antibiotics for more than 24 hours. There was a significant improvement in overall survival when compared with our previous series. As before, almost one fourth (24%) of our isolates were not among those included in the pneumococcal vaccine presently available. Antibiotic prophylaxis should be considered in high risk patients.

Adolescent↗
PubMedDate not supplied

Pneumococcal vaccine trials in Papua New Guinea: relationships between epidemiology of pneumococcal infection and efficacy of vaccine.

Field trials in Papua New Guinea have shown that pneumococcal capsular polysaccharide vaccine protects children less than 2 years of age from death due to acute lower respiratory infections (ALRI). The vaccine appears to reduce mortality by preventing bacteremia. Evidence suggests that highly invasive "adult" pneumococcal serotypes are comparatively more important as a cause of ALRI in developing countries where ALRI-related mortality is higher than in North America. Capsular polysaccharide vaccines are more likely to be immunogenic for these serotypes than for the "pediatric" serotypes. The evaluation of pneumococcal vaccines in areas where mortality is high should have the highest priority. For such trials investigators should, at minimum, define epidemiologic circumstances in terms of (1) the invasive serotypes of pneumococci, (2) the protective levels of antibody, (3) the antibody response to vaccination, and (4) the general immune status of the population.

Adult↗
PubMedDate not supplied

Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London, 12 December 1996. HIV and pneumococcal infection in Africa. Clinical, epidemiological and preventative aspects.

The pneumococcus (Streptococcus pneumoniae) is a leading cause of morbidity and mortality in tropical and temperate climes. Despite being well recognized as an important pathogen associated with human immunodeficiency virus (HIV) infection in industrialized countries, this interaction has received little attention in Africa. Work on this subject carried out in Nairobi (Kenya) over a period of 5 years (1989-1993) is reviewed. Among epidemiological aspects, nasopharyngeal carriage is discussed and the increased risks for invasive disease and pneumococcal pneumonia, recorded in cross-sectional and prospective studies, are highlighted. Clinical aspects include the wider spectrum of HIV-related invasive pneumococcal disease that is seen in adults, emphasizing that, even with high rates of penicillin resistance, standard benzylpenicillin therapy is effective if started early in disease. Many patients, however, present late in the course of illness and mortality rates for pneumococcal pneumonia are higher in HIV-infected adults. Pneumococcal disease is preventable in immunocompetent adults and, although no efficacy data are available, vaccination is recommended for all HIV-infected adults in industrialized countries. Current research investigating the efficacy of pneumococcal vaccination in HIV-infected adults living in Entebbe (Uganda) and clients of The AIDS [acquired immune deficiency syndrome] Support Organization (TASO) is summarized. The results of this 'double-blind' placebo-controlled trial will be known in July 1998.

Adult↗
PubMed2002

Epidemiology of invasive pneumococcal infection in Taiwan: antibiotic resistance, serogroup distribution, and ribotypes analyses.

From July, 1998, to June, 1999, pneumococcal isolates from 288 patients with invasive disease in Taiwan were serogrouped and tested for their susceptibility to various antibiotics. Automated ribotyping was used to study their molecular epidemiology. The mortality rate among those > or = 65 years was higher than those 18 or 19-64 years (p < 0.001). The total incidence of infection was significantly higher during the cooler season than the warmer season (p = 0.017). Among strains isolated from children aged < or = 18 years, 76% were not susceptible to penicillin, a rate that was significantly higher (p < 0.001) than that for adults (45%), as was the susceptibility to azithromycin, erythromycin, and trimethoprim-sulfamethoxazole (p < 0.005). The most prevalent serogroup encountered in the invasive isolates was 23, followed by 6, 14, 19, and 3. Isolation of Streptococcus pneumoniae in cerebrospinal fluid was at high rate in children under 5 years (p = 0.00012). Molecular typing revealed a high degree of polymorphism among the isolates. Among serogroup 23 and 19 isolates, a high proportion had the same ribotypes, the Taiwan23F-15 and Taiwan19F-14 isolates, suggesting the circulation of a Taiwanese epidemic strain. In Taiwan, S. pneumoniae isolates should be tested for their resistance profile for children < or = 18 years old, as these are more likely to harbor high-level resistance. Control of pneumococcal infection with the 7-valent-conjugated vaccine should also be considered because it is estimated that it would cover nearly 90% of the serotypes among pediatric invasive disease.

Adolescent↗