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Protein-sparing therapy during pneumococcal infection in rhesus monkeys.

A model was developed in the rhesus monkey to determine if the marked wasting of body proteins associated with sepsis could be prevented by an intravenous supply of various nutritional substrates. All monkeys were given a basic infusion of 0.5 gm of amino acid nitrogen/kg body weight via an indwelling catheter in the jugular vein. Three groups were given diets with no added calories, 85 calories/kg from dextrose or 85 calories from lipid. In each group, six monkeys were inoculated with 3 x 10(8) Streptococcus pneumoniae and four with heatkilled organisms. In the monkeys infused with the amino acids alone, pneumococcal sepsis resulted in a fourfold increase in loss of body proteins compared with calorie-restricted controls. Addition of 85 calories/kg/day of either dextrose or lipid reduced body wasting associated with infectious disease. The calories from lipid were utilized bythe septic host as a source of energy, with a slightly reduced efficiency when compared with the isocaloric infusion of dextrose. The nitrogen sparing of the fat emulsion could not be accounted for by its glycerol content. Therefore, the septic monkey seemed to utilize fatty acids as an energy substrate. It appears that the carbohydrate calories tend to favor the synthesis of peripheral proteins (associated mainly with skeletal muscle), while lipid calories favor synthesis of visceral proteins such as plasma albumin and acute-phase proteins.

Amino Acids

Effects of pneumococcal infection on rat liver microsomal enzymes and lipogenesis by isolated hepatocytes.

Modification in the enzymatic complement and lipogenic functions of rat liver endoplasmic reticulum (ER) were shown to occur during pneumococcal sepsis. Glucose-6-phosphatase, 5'nucleotidase, esterase, and NADPH cytochrome C reductase decreased in activity by as much as 50% with respect to controls. Hydroxymethylglutaryl-CoA and NADH cytochrome C reductases were increased 6-and 2-fold, respectively. Alkaline phosphatase and inosine-5'-diphosphatase did not differ with respect to fasted controls. The lipogenic capacity of the ER was shown to be enhanced. In vitro [14C]acetate incorporation into cholesterol and other lipids by hepatocytes isolated from infected rats was increased 2-to 10-fold. It is concluded that the flow of acetyl-CoA in liver cell of Streptococcus pneumoniae-infected rats is toward lipogenesis rather than ketogenesis.

Animals

Counter-current immunoelectrophoresis for the diagnosis of pneumococcal chest infection.

Counter-current immunoelectrohporesis is a rapid sensitive method for detecting pneumococcal capsular antigens in sputum. A result can be obtained within 45 minutes. The optimum conditions for performing the test are given. Counter-current immunoelectrophoresis works with all the 33 pneumococcal antigens tested except type 14. Better precipitin lines are obtained when the gel-support is acid (pH 6-6) than when it is alkaline (pH 8-6). Omniserum is as effective as group-specific sera for the identification of pneumococcal capsular antigens. The findings suggest that pneumococcal infection was present in 44% of 300 unselected suspected chest infections. Culture for pneumococci was positive in only 15% of these cases. The clinical importance of these findings is still being studied but our experience has shown that patients with chest infections should have effective antipneumococcal antibiotics as part of their regimen and that the laboratory diagnosis may be made quickly and accurately by counter-current immunoelectrophoresis.

Antigens, Bacterial

The role of cytolysin in pneumococcal ocular infection.

A highly purified preparation of pneumococcal cytolysin was responsible for the corneal damage that ensued upon intra-corneal injection of crude cell extract into the rabbit eye. The lysin may produce this pathologic finding by effecting activation or release of corneal degradative enzymes.

Animals

Intracellular survival of Streptococcus pneumoniae in human alveolar macrophages is augmented with HIV infection.

People Living with HIV (PLHIV) are at an increased risk of pneumococcal pneumonia than HIV-uninfected adults, but the reasons for this are still not well understood. We investigated whether alveolar macrophages (AM) mediated control of pneumococcal infection is impaired in PLHIV compared to HIV-uninfected adults. We assessed anti-bactericidal activity against Streptococcus pneumoniae of primary human AM obtained from PLHIV and HIV-uninfected adults. We found that pneumococcus survived intracellularly in AMs at least 24 hours post ex vivo infection, and this was more frequent in PLHIV than HIV-uninfected adults. Corroborating these findings, in vivo evidence showed that PLHIV had a higher propensity for harboring S. pneumoniae within their AMs than HIV-uninfected adults. Moreover, bacterial intracellular survival in AMs was associated with extracellular propagation of pneumococcal infection. Our data suggest that failure of AMs to eliminate S. pneumoniae intracellularly could contribute to the increased risk of pneumococcal pneumonia in PLHIV.

Adult

Severe infection due to Streptococcus pneumoniae in asplenic renal transplant patients.

The medical records of 293 patients who underwent renal transplantation were analyzed for the occurrence of Streptococcus pneumoniae and Haemophilus influenzae infections in relation to splenectomy. Splenectomy was done in 236 (81%) graft recipients before or concomitant with transplantation. Bacteremia developed in five and fulminant sepsis in two from 3 to 32 months after splenectomy. No serious infections with these organisms occurred in the nonsplenectomy group. These results suggest that asplenia may be an additional factor predisposing transplant patients to serious infection. Prevention of these serious pneumococcal infections may be possible with polyvalent pneumococcal vaccine.

Adult

[Current place of the Pneumococcus in infectious pathology].

This work regroups an important number of acute pneumococcal infections with septicemia, which recalls that these infections are of current importance, owing to their frequency and poor prognosis. Present diagnositc, clinical, radiological and bacteriological methods are discussed and criticised. An important, but not exclusive place, is reserved for routine blood culture. Finally, the authors discuss future prospects of acute pneumococcal infections, mainly diagnostic and prophylactic.

Acute Disease

Detection of pneumococcal polysaccharide in the sputum of patients with pneumococcal pneumonia by counterimmunoelectrophoresis.

Each of 41 patients with bacterial pneumonia was placed into 1 of 4 categories based on the relative clinical certainty of the diagnosis of pneumococcal pneumonia. The frequency of pneumococcal polysaccharide in the sputum by counterimmunoelectrophoresis (CIE) was then noted for each diagnostic category of patients. Detection of pneumococcal polysaccharide in sputum correlated with the diagnostic certainty of pneumococcal pneumonia, while results of culture of sputum were less indicative of pneumococcal infection. Saliva of 83 normal individuals failed to give positive tests for pneumococcal polysaccharide despite the presence of alpha-hemolytic streptococci on culture. Furthermore, the mere presence of pneumococci in cultures did not predict a positive test for polysaccharide by CIE nor did the absence of pneumococci mean that polysaccharide would not be detected. This study suggests that detection of pneumococcal polysaccharide appears more rapid, more sensitive, and more specific than sputum cultures in diagnosing pneumococcal infection of the lung.

Counterimmunoelectrophoresis

Pneumococcal isolations from patients with pneumonia and control subjects in a prepaid medical care group.

The incidence of pneumococcal infections and pneumonia among the 150,000 members of a prepaid medical care group in Seattle was assessed by an intensive study of outpatients for one year from June 1971 through May 1972. Respiratory specimens (sputum, pharyngeal, and nasal) from patients with pneumonia or febrile respiratory disease and from age- and sex-matched control subjects were cultured for pneumococci on media and in mice. Total rate of pneumonia was 11 per 1,000. Twenty-four per cent of patients with pneumonia and 12 per cent of control subjects carried pneumococci. The patients with pneumonia from whom the pneumococcus was isolated did not differ clinically on average from those without such isolates. Lobar and bacteremic pneumonia were extremely rare. The rate of pneumococcal infections and carriers was highest in the spring. Although young children had the highest rate of pneumonia from all causes there was no difference in the isolation rate between ill children and control children. The highest rate attributable to pneumococci was in those larger than 40 years of age. Pneumococcal carrier rates were much lower than those reported in the 1930s. Thirty-nine per cent of patients with pneumonia had evidence of viral or mycoplasmal infection, as determined primarily by serologic methods. Pneumococcal pneumonia was not a serious problem in this average, employed population in Seattle.

Adolescent

Mycoplasma pneumoniae and the aetiology of lobar pneumonia in northern Nigeria.

Over a six-month period we studied 74 adult Nigerians who presented consecutively to Ahmadu Bello University Teaching Hospital, Zaria, with lobar or segmental pneumonia. Pneumococcal infection was diagnosed in 50% by the detection of pneumococcal polysaccharide antigen in serum or purulent sputum: 24% had pneumococcal antigenaemia. Twelve patients had evidence of Mycoplasma pneumoniae infection and half of these also had pneumococcal infection. The suggestion that M pneumoniae respiratory infection may predispose to serious bacterial pneumonia is discussed. The initial clinical and radiological features were similar in the pneumococcal and M pneumoniae groups. Raised cold agglutinin titres were not a reliable indication of M pneumoniae infection, perhaps due to altered autoantibody production in Nigerians. Pneumonia was commoner in the dry season, probably related to depressed nasopharyngeal defences caused by drying. Less common causes of lobar pneumonia that were found are also discussed and no cases of legionnaires' disease were identified.

Adult

Host defense against the pneumococcus in T-lymphocyte-deficient, nude mice.

Resistance to pneumococcal infection was tested in T-lymphocyte-deficient, nude (nu/nu) mice. Pneumococcal serum opsonizing activity, in vivo phagocytosis of the pneumococcus, and the mean lethal dose for the pneumococcus were all found to be the same in nude mice as in control (+/+) mice. T-lymphocytes do not appear to play a significant role in the host's defense against the pneumococcus.

Animals

Pneumococcal disease and its prevention with polyvalent pneumococcal polysaccharide vaccines--a review.

Polyvalent pneumococcal polysaccharide vaccines have been shown to be safe, immunogenic and efficacious and are becoming available for use in patients at high risk of developing pneumococcal infections. Precise estimates of the role of the pneumococcus in human respiratory disease are difficult to obtain, as this organism is also a frequent commensal of the upper respiratory tract; and as the optimal techniques for the identification and proof of its role are not widely used. Nevertheless, the pneumococcus remains the principal cause of adult pneumonia and paediatric otitis media, and is also an important cause of death from bacteremia and meningitis. At present it seems likely that in Australia these vaccines will be most useful amongst people over the age of 50 years, those with chronic systemic disease, alcoholics, splenectomized individuals and disadvantaged groups such as Australian aborigines, all of whom are particularly susceptible to pneumo-coccal bacteremia which has a considerable mortality rate. The possibility of preventing pneumococcal otitis media in childhood is still being evaluated. Studies of the role played by the various pneumococcal serotypes in Australian populations are urgently needed.

Adult

Immunologic studies in pneumococcal disease.

Many patients die from pneumococcal disease despite the availability of effective antimicrobial agents. Immunologic studies including detection, typing, and quantitation of serum pneumococcal capsular polysaccharide (PCP) antigen by counterimmunoelectrophoresis (CIE), quantitation of PCP antibody by radioimmunoassay (RIA), and quantitation of serum complement components C3, C4, and C3PA and serum immunoglobulins IgG, IgM, and IgA by the radial immunodiffusion technique of Mancini were performed with the sera of 18 patients. Five patients died (group I), and 13 survived (group II) pneumococcal infection. Both groups were comparable in age, underlying disease, and leukopenia on admission. All patients of group I and 10 of 13 (77%) of group II patients were bacteremic. Two patients in each group had an extrapulmonary focus infection. PCP antigen was detected in the sera of all group I and nine of 13 group II patients. PCP antigen levels were larger than or equal to 15 microng/ml in four of five group I and two of 13 group II patients (p = 0.022). Levels of antibody to PCP exceeded 100 ng/ml of antibody nitrogen (AbN) in 10 of 12 group II and one of five group I patients (p = 0.027) during the course of illness. All group I patients and three of 12 group II patients had decreased levels of one or more complement components on admission (p less than 0.01). One or more complement components remained decreased until death in four group I patients but returned to normal or elevated levels in all group II patients. No difference in serum immunoglobulin concentrations were found.

Adult