Guidelines for the prevention of sepsis in asplenic and hyposplenic patients.

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has a mortality of up to 50%. The spectrum of causative organisms is evolving as are recommended preventive strategies, which include education, prophylactic and standby antibiotics, preventive immunizations, optimal antimalarial advice when visiting endemic countries and early management of animal bites. However, there is evidence that adherence to these strategies is poor. Consensus-updated guidelines have been developed to help Australian and New Zealand clinicians and patients in the prevention of sepsis in asplenic and hyposplenic patients.

Ozbug: an email mailing list for physicians that works.

Very few studies of the quality of electronic mailing lists have been published. Ozbug was established in 1997 as a moderated and closed mailing list for infectious diseases physicians in Australia and New Zealand. A broad range of clinical and professional issues is discussed by -subscribers. An email survey of subscribers in 2002 indicated a high degree of satisfaction with the service.

Streptococcus pneumoniae PstS production is phosphate responsive and enhanced during growth in the murine peritoneal cavity.

Differential display-PCR (DDPCR) was used to identify a Streptococcus pneumoniae gene with enhanced transcription during growth in the murine peritoneal cavity. Northern dot blot analysis and comparative densitometry confirmed a 1.8-fold increase in expression of the encoded sequence following murine peritoneal culture (MPC) versus laboratory culture or control culture (CC). Sequencing and basic local alignment search tool analysis identified the DDPCR fragment as pstS, the phosphate-binding protein of a high-affinity phosphate uptake system. PCR amplification of the complete pstS gene followed by restriction analysis and sequencing suggests a high level of conservation between strains and serotypes. Quantitative immunodot blotting using antiserum to recombinant PstS (rPstS) demonstrated an approximately twofold increase in PstS production during MPC from that during CCs, a finding consistent with the low levels of phosphate observed in the peritoneum. Moreover, immunodot blot and Northern analysis demonstrated phosphate-dependent production of PstS in six of seven strains examined. These results identify pstS expression as responsive to the MPC environment and extracellular phosphate concentrations. Presently, it remains unclear if phosphate concentrations in vivo contribute to the regulation of pstS. Finally, polyclonal antiserum to rPstS did not inhibit growth of the pneumococcus in vitro, suggesting that antibodies do not block phosphate uptake; moreover, vaccination of mice with rPstS did not protect against intraperitoneal challenge as assessed by the 50% lethal dose.

Peritoneal culture alters Streptococcus pneumoniae protein profiles and virulence properties.

We have examined the properties of Streptococcus pneumoniae cultured in the murine peritoneal cavity and compared its virulence-associated characteristics to those of cultures grown in vitro. Analysis of mRNA levels for specific virulence factors demonstrated a 2.8-fold increase in ply expression and a 2.2-fold increase in capA3 expression during murine peritoneal culture (MPC). Two-dimensional gels and immunoblots using convalescent-phase patient sera and murine sera revealed distinct differences in protein production in vivo (MPC). MPC-grown pneumococci adhered to A549 epithelial cell lines at levels 10-fold greater than those cultured in vitro.

Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for Pneumococcal pneumonia.

IgG to capsular polysaccharide (CPS) of Streptococcus pneumoniae is thought to provide the greatest degree of protection against pneumococcal disease. Serum obtained at hospital admission from 14 (27%) of 51 patients with bacteremic pneumococcal pneumonia and 11 (37%) of 30 with nonbacteremic pneumococcal pneumonia contained IgG to CPS of the infecting serotype; these percentages are similar to the prevalence of IgG to CPS in a control population. However, when compared with antibody from healthy adults, this IgG had far less capacity to opsonize the infecting pneumococcal serotype for phagocytosis in vitro by normal human polymorphonuclear leukocytes or to protect mice against experimental challenge. Failure to opsonize correlated closely with failure to protect mice, and each of these parameters correlated well with poor avidity for CPS. Future vaccine studies may need to examine the functional capacity of antibodies as a surrogate for infection, in addition to measuring their concentration in serum.

Genetic relatedness among nontypeable pneumococci implicated in sporadic cases of conjunctivitis.

Nontypeable Streptococcus pneumoniae is a common cause of epidemic conjunctivitis. A previous molecular fingerprinting study identified a clone of nontypeable pneumococcus that was responsible for a recent outbreak of conjunctivitis. In the present study, we examined the extent to which pneumococci that cause sporadic cases of conjunctivitis are related to this epidemic strain. Using arbitrarily primed BOX-PCR, we have determined that, of 10 nontypeable pneumococci causing sporadic conjunctivitis, 5 were clonal and closely related to a previous outbreak strain, whereas 5 others were genetically diverse.

A brief history of the pneumococcus in biomedical research.

Because of its importance in human disease, Streptococcus pneumoniae has been the subject of intensive study at both the clinical and basic scientific levels for more than a century. In a number of instances, important advances in basic biology have resulted. Among these are the development of Gram's stain for identification of bacteria in patient specimens, investigations of the role of the bacterial capsule in resistance to phagocytosis by cells of the host immune system, demonstration that molecules other than proteins are capable of eliciting host humoral immune responses, development of safe and effective vaccines composed of isolated bacterial exopolysaccharides, confirmation of the efficacy of penicillin against serious gram-positive infections, and perhaps most important confirmation that DNA alone encodes genetic information.

IgG responses to protein-conjugated pneumococcal capsular polysaccharides in persons who are genetically incapable of responding to unconjugated polysaccharides.

We have previously shown that the capacity to make IgG to pneumococcal capsular polysaccharides (PCPs) is inherited as an autosomal, mixed codominant trait. The purpose of this study was to determine whether this genetically determined unresponsiveness could be overcome by injection of protein-conjugated pneumococcal vaccines. Seven healthy adults who had failed to produce IgG to five or more of 10 representative PCPs after receiving pneumococcal vaccine and whose parents, siblings, and/or offspring had a similar lack of responsiveness received a series of protein-conjugated polysaccharide vaccines. Excellent IgG responses to most of the PCPs tested were eventually observed in five of the seven subjects after they received octavalent diphtheria toxoid-conjugated vaccine. Administration of certain protein-conjugated PCPs leads to IgG responses in some persons who lack the capacity to respond to unconjugated PCPs.

Enteroaggregative Escherichia coli as a potential cause of diarrheal disease in adults infected with human immunodeficiency virus.

Stools of 68 human immunodeficiency virus (HIV)-infected adults with diarrhea and 60 without diarrhea were examined for enteroaggregative Escherichia coli (EAggEc) by HeLa cell adherence assay. EAggEc were present in stools of 30 patients with and 18 without diarrhea (P = .05). CD4 cell counts of patients with EAggEc and diarrhea were significantly lower than those of patients with EAggEc without diarrhea (P = .02). There was no difference in the mean duration of diarrheal symptoms or in the number of stools per day between patients with EAggEc and those without. None of the EAggEc strains were positive by polymerase chain reaction for adherence fimbria, but 11 strains were positive for EAggEc heat-stable toxin EAST/1. Of the EAggEc strains, 51% were resistant to trimethoprim-sulfamethoxazole and 65% were resistant to ampicillin. EAggEc may be a pathogen in HIV-infected patients with diarrhea; HIV-infected patients with EAggEc appear to be more symptomatic when HIV disease is more advanced.

BOX-polymerase chain reaction-based DNA analysis of nonserotypeable Streptococcus pneumoniae implicated in outbreaks of conjunctivitis.

Nonserotypeable isolates predominate in epidemic conjunctivitis caused by Streptococcus pneumoniae. Previous evaluations of outbreaks of pneumococcal conjunctivitis have relied on epidemiologic factors and the nontypeability of the isolates to infer that a single clone was involved. In the present study, BOX-polymerase chain reaction DNA analysis was used to characterize nonserotypeable S. pneumoniae isolated by conjunctival culture during a recent conjunctivitis outbreak and to compare these isolates with those from outbreaks described earlier. The recent outbreak was caused by a single pneumococcal clone. Outbreaks in separate parts of the United States in 1980-1981 were all caused by the same clone. Cluster analysis revealed a high degree of genetic relatedness among isolates causing conjunctivitis compared with that among other nonserotypeable S. pneumoniae, with the closest relatedness being found among the 1996 and 1980-1981 conjunctival isolates.

Emergence of antibody to capsular polysaccharides of Streptococcus pneumoniae during outbreaks of pneumonia: association with nasopharyngeal colonization.

Antibody to pneumococcal capsular polysaccharides (PPS) of Streptococcus pneumoniae plays a major role in protecting the host against pneumococcal infection. A variable proportion of healthy adults have antibody to PPS, often in the absence of recognized pneumococcal infection. To determine whether exposure to pneumococci or colonization by pneumococci, or both, stimulates the emergence of antibody to PPS, we studied outbreaks of pneumonia at two military camps. Of the men who were present at a military training camp during an outbreak of pneumonia due to S. pneumoniae serotype 1 but who did not develop pneumonia, 27.8% had IgG antibody to PPS 1, whereas only 3.6% of controls had this antibody. In another outbreak caused by S. pneumoniae serotypes 7F and 8, 35.9% of asymptomatic soldiers who had nasopharyngeal colonization by one of these strains had antibody to the relevant PPS, and another 30.8% who originally did not have antibody developed it within 30 days; thus, 66.7% of these soldiers had antibody to the relevant PPS. These data show that serotype-specific antibody promptly appears following exposure to an outbreak of pneumococcal pneumonia and is probably mediated through acquisition of nasopharyngeal pneumococcal carriage.