Role of Pneumolysin's complement-activating activity during pneumococcal bacteremia in cirrhotic rats.
(25/2520)
We investigated the role of pneumolysin's complement-activating activity during Streptococcus pneumoniae bacteremia in a hypocomplementemic, cirrhotic host. Isogenic mutant pneumococcal strains, in which pneumolysin was expressed from a plasmid, were used. These strains included H+C+, expressing wild-type pneumolysin with both cytolytic and complement-activating activity; PLY-, carrying the plasmid without the pneumolysin gene; and, H+C-, expressing pneumolysin with cytolytic activity only. In control rats, intravenous infection with 2.0 x 10(7) CFU of H+C+ per ml of blood resulted in a decrease in bacteremia of 3.5 log units by 18 h postinfection and 55% mortality. By contrast, cirrhotic rats infected similarly with the H+C+ strain demonstrated a 0.2-log-unit increase in bacteremia by 18 h postinfection and 100% mortality. Both control and cirrhotic rats cleared the PLY- strain more effectively from their bloodstreams by 18 h postinfection (6.2 and 5. 6 log unit decreases, respectively). Infection with the PLY- strain also resulted in low mortality (0 and 14%, respectively) for control and cirrhotic rats. When infected with the H+C- strain (without complement-activating activity), both groups cleared the organism from their bloodstreams nearly as well as they did the PLY- strain. Furthermore, the mortality rate for control and cirrhotic rats was identical after infection with the H+C- strain. These studies suggest that pneumolysin production contributes to decreased pneumococcal clearance from the bloodstream and higher mortality in both control and cirrhotic rats. However, pneumolysin's complement-activating activity may uniquely enhance pneumococcal virulence in the hypocomplementemic, cirrhotic host. (+info)
Look, Ma! No pneumococcus!
(26/2520)
Pneumococcal diseases, caused by the bacterium Streptococcus pneumoniae, include pneumonia and otitis media, which accounts for some 12 million doctor visits per year in the United States alone. Each year around the world, pneumococcus causes 1.2 million deaths due to pneumonia, 39% of which are in children under the age of five. In a three-year Phase III clinical trial involving 38,000 children, in which half of the infants received a new pneumococcal vaccine and half received a placebo vaccine, the new vaccine demonstrated an efficacy rate of 100% against bacterial meningitis and bacteremia, the two most deadly pneumococcal afflictions. (+info)
Bacterial vaccines and serotype replacement: lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae.
(27/2520)
Conjugate vaccines have reduced the incidence of invasive disease caused by Haemophilus influenzae, type b (Hib), in industrialized countries and may be highly effective against Streptococcus pneumoniae. However, the serotype specificity of these vaccines has led to concern that their use may increase carriage of and disease from serotypes not included in the vaccine. Replacement has not occurred with the use of Hib vaccines but has occurred in trials of pneumococcal vaccines. Mathematical models can be used to elucidate these contrasting outcomes, predict the conditions under which serotype replacement is likely, interpret the results of conjugate vaccine trials, design trials that will better detect serotype replacement (if it occurs), and suggest factors to consider in choosing the serotype composition of vaccines. (+info)
Respiratory diseases among U.S. military personnel: countering emerging threats.
(28/2520)
Emerging respiratory disease agents, increased antibiotic resistance, and the loss of effective vaccines threaten to increase the incidence of respiratory disease in military personnel. We examine six respiratory pathogens (adenoviruses, influenza viruses, Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumoniae, and Bordetella pertussis) and review the impact of the diseases they cause, past efforts to control these diseases in U.S. military personnel, as well as current treatment and surveillance strategies, limitations in diagnostic testing, and vaccine needs. (+info)
In-vitro activities of 16 non-beta-lactam antibiotics against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae.
(29/2520)
MICs of 16 non-beta-lactams were determined by agar dilution for 283 penicillin-susceptible, 122 intermediate and 23 fully penicillin-resistant isolates of pneumococci. Penicillin-resistant pneumococci were more likely to be resistant to tetracyclines, macrolides and related compounds. In the latter group, quinupristin/dalfopristin was the only compound whose activity was not influenced by penicillin resistance. Among the fluoroquinolones, clinafloxacin and trovafloxacin showed excellent activity. Strains resistant to macrolides, tetracycline and penicillin were concentrated in serogroups 6, 9, 14, 19 and 23. (+info)
Epidemiology of Streptococcus pneumoniae infections at the Edinburgh City Hospital: 1980-95.
(30/2520)
We present data on pneumococcal isolates collected from deep and superficial sites over a 16-year period at the Edinburgh City Hospital. The 10 most frequent serotypes overall were 6, 19, 11, 9, 3, 14, 1, 15 and 18 in children and 19, 23, 6, 6, 9, 11 3, 15, 14, 22 and 4 in adults. Over 88% (2588/2932, 88.3%) of these pneumococci were of serotypes represented in the 23-valent polysaccharide pneumococcal vaccine. Within the 20-45 years age group, 228/434 (52.5%) of specimens were from HIV-infected individuals. The isolations showed a seasonal distribution with peaks in February and troughs in September. The annual numbers of blood culture isolates showed an upward trend. Recurrent isolations were more frequent in HIV-infected individuals (49/132, 37%) than in non-HIV-infected individuals (218/2421, 9.9%) (relative risk = 5.05, 95% confidence interval, 3.46-7.03). The prevalence of resistance to penicillin and erythromycin was lower than that reported in other parts of the UK. (+info)
Dissemination of a chloramphenicol- and tetracycline-resistant but penicillin-susceptible invasive clone of serotype 5 Streptococcus pneumoniae in Colombia.
(31/2520)
A national surveillance conducted in Colombia between 1994 and 1996 identified serotype 5 Streptococcus pneumoniae as the second most frequent cause of invasive disease in children younger than 5 years of age. All 43 serotype 5 isolates collected during this period were shown to be susceptible to penicillin, erythromycin, cefotaxime, and vancomycin, but most (38 of 43, or 88%) were highly resistant to chloramphenicol. In order to clarify a possible genetic relatedness among these isolates, additional microbiological and molecular characterizations were performed. Most (40 of 43, or 93%) of the isolates were found to be resistant to tetracycline. Pulsed-field gel electrophoresis (PFGE) patterns of chromosomal DNAs revealed that all the 43 isolates were closely related and that 38 of the 43 isolates were representatives of a "Colombian clone" of S. pneumoniae isolates which were recovered throughout the 3-year surveillance period from patients in 13 hospitals located in five Colombian cities. Isolates belonging to this Colombian clone were resistant to chloramphenicol and tetracycline, hybridized with the cat and tetM DNA probes in the same 340-kb SmaI fragment, and had identical PFGE patterns after both SmaI and ApaI digestions. (+info)
The epidemiology of pneumococcal infection in children in the developing world.
(32/2520)
Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain. (+info)