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[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

Role of non-capsulated Haemophilus influenzae as a respiratory pathogen in children.

During a 12-month surveillance period from 1981-1982, non-capsulated Haemophilus influenzae was detected in nasopharyngeal aspirates from 64 (14%) of the 449 children hospitalized for middle or lower respiratory infection. An antibody response to H. influenzae was indicated in 15(23%) of the 64 patients with H. influenzae present in nasopharyngeal aspirate and in 10 (3%) of the 385 patients with a negative finding. Thus, serological evidence of H. influenzae infection was demonstrated in 25 (6%) of all the 449 children with respiratory infection. Of 13 patients with cultures positive for H. influenzae acute otitis media, an antibody response was seen in only 4 (30%) patients. H. influenzae infection was associated with infections caused by other microbes in 20 children (80%), with viral infections in 60% and with pneumococcal infections in 24% of cases. An infection focus was present in 15 (79%) of the 25 patients with H. influenzae infection; pneumonia was present in 10 cases and acute otitis media in 9 cases. Non-specific laboratory evidence of bacterial infection was seen in 11 patients (58%); C-reactive protein was increased in 7 and erythrocyte sedimentation rate in 9 patients. It is concluded that non-capsulated H. influenzae is a genuine respiratory pathogen in children. H. influenzae infections appear to be secondary to preceding viral or other bacterial infections in children who are carriers of this strain.

Adolescent

Overwhelming pneumococcal sepsis 25 years after splenectomy.

In a 47-year-old healthy male, the syndrome of overwhelming pneumococcal sepsis, associated with diffuse intravascular clotting, appeared 25 years after a post-traumatic splenectomy. Although no other disease was present, the course was fulminant and the outcome fatal. Splenectomy for any condition and in all ages, augments the risk to severe pneumococcal infection.

Humans

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

Specific metabolic effects imposed by Streptococcus pneumoniae upon the response to femoral fracture in the rat.

The possible potentiation of an infection upon the metabolic consequences of trauma was tested in rats using a 2 X 2 block design which included control, femoral fracture, pneumococcal infection, and fracture plus infection groups. Infection introduced unique metabolic effects different from those of starvation, femoral fracture, or both together. Infection-induced effects included an accelerated conversion of 14C-alanine to glucose, higher serum haptoglobin, alpha2-macrofetoprotein, copper, and ceruloplasmin values, and lower serum iron, zinc, and transferrin concentrations. The first three of these infection-induced effects were diminished in rats with a femoral fracture. No measured effect of infection was increased in traumatized rats.

Animals

[Phlebitis of infectious etiology].

Various infections are sometimes at the origin of phlebitis. Because of the different therapeutic consequences, this etiology should be considered whether it is a case of deep phlebitis of a limb, migratory recurrent phlebitis, or the type of phlebitis called "iron wire". The principal diseases that may lead to phlebitis are : tuberculosis, typhoid fever, rickettsiosis, and streptococcal, staphylococcal, and pneumococcal infections. Certain viruses may have a role but so far there is no formal proof. Focal pathology of dental or tonsillar origin involves in some cases an aseptic venous lesion. Bacterial or mycotic suppurative thrombophlebitis related to an intravenous catheter is the price paid for the use, often unnecessarily, of this method of perfusion.

Bacterial Infections

Alternative C3 pathway activiation in pneumococcal glomerulonephritis.

Glomerulonephritis following pneumococcal infection has been observed, but possible immunopathologic mechanisms have not been adequately explored. Multiple serologic studies as well as light, immunofluorescence and electron microscopic evaluation of kidney biopsy tissue from a 4 year old girl with pneumococcal glomerulonephritis were performed. Clinical studies at the onset of the disease showed normal serum C3 and C4 levels (third and fourth components of complement) with progression to selective C3 hypocomplementemia from days 2 to 58. A serum factor capable of breaking down C3 in normal human serum was present during the period of maximum C3 hypocomplementemia. Renal glomerular histology revealed a mesangial proliferative glomerulonephritis. Glomerular bound C3 and type 14 pneumococcal antigen were associated with similar, but less extensive, deposits of properdin. Minimal immunoglobulin M (IgM) and C4 were seen, but immunoglobulin G (IgG) and fibrinogen were absent. Ultrastructurally, subepithelial "humps" and intramembranous electron dense deposits were noted. It is hypothesized that the pneumococcal polysaccharide can activate the alternate complement pathway and may be responsible for a limited course of glomerulonephritis.

Antigens, Bacterial

Concurrent primary pneumococcemia, disseminated intravascular coagulation, and sickle cell anemia.

Fulminant pneumococcal infections are rare in teen-agers with sickle cell anemia. A 16-year-old black male with sickle cell anemia was treated as an outpatient for cryptogenic pain crisis, which delayed antibiotic therapy for primary pneumococcal septicemia for seven hours. This patient did not appear ill upon initial presentation but rapidly developed disseminated intravascular coagulation and died.

Adolescent

Endometritis and neonatal sepsis due to Streptococcus pneumoniae.

Attention is called to the rarely described clinical entity of pneumococcal infection involving both mother and neonate. A case is described in which neonatal sepsis and puerperal endometritis were documented by isolating Streptococcus pneumoniae type 3 from both mother and child. Clinical implications and a review of relevant literature are briefly discussed.

Adolescent

Modification by fiber of toxic dietary effects.

There is evidence that type of diet may affect the course of chemical carcinogenesis. In experiments with acetylaminofluorene, rats maintained on stock diet exhibit fewer tumors than do rats fed semi-purified diets. Rats fed stock diet augmented with high levels of sodium cyclamate (2.5-10%), amaranth (5%) or Tween (15%) showed normal weight gain, whereas addition of these toxicants to a fiber-free basal diet caused severely restricted weight gain and decreased survival. The latter effect can be overcome by addition of 10% pectin, alfalfa or cellulose to the basal diet. On the other hand, mice fed a fiber-free diet survived pneumococcal infection better than did mice fed modified stock diets. The mechanism(s) by which fiber affects carcinogenicity or toxicity are unelucidated. The effect of fiber and other aspects of diet on drug action is an area of research that should be developed.

2-Acetylaminofluorene

Early deaths in Jamaican children with sickle cell disease.

In Jamaican children with homozygous sickle cell (SS) disease diagnosed at birth two-year survival was 87%, compared with 95% in children with sickle cell-haemoglobin C (CS) disease, and 99% in normal controls. Death among those with SS disease occurred most often between the ages of 6 and 12 months. Principal causes were acute splenic sequestration and pneumococcal infection. Neonatal diagnosis of haemoglobinopathies must be followed by close observation if mortality is to be reduced by early diagnosis and treatment of these complications.

Age Factors

Epidemiological studies of Streptococcus pneumoniae in infants: methods of isolating pneumococci.

A prospective study of the natural history of pneumococcal infection, which involves serial culture studies in healthy infants from 6 weeks of age onward, is in progress in our laboratory. This report describes results of a comparison of several methods for the isolation and identification of Streptococcus pneumoniae from the nasopharynges and throats of these infants. Sheep blood agar, sheep blood agar with gentamicin sulfate (gentamicin agar), and mouse inoculation with 4-h broth cultures were used. Gentamicin agar proved superior to plain sheep blood agar as a solid culture medium, especially in enhancing the recovery of pneumococci from throat cultures. With gentamicin agar, similar carrier rates were found for both culture sites (nasopharynx and throat). In addition, gentamicin agar proved superior to mouse inoculation for the recovery of carrier strains from 131 nasopharyngeal culture samples processed by both methods. Sixty of 131 samples were positive for pneumococci, 25% of which would have been missed had mouse inoculation alone been used. In only three instances did we recover a strain by mouse inoculation that failed to grow on gentamicin agar; conversely, 15 strains were isolated on gentamicin agar but could not be recovered from mice. The latter observation might be explained by the fact that certain carrier strains may be relatively mouse avirulent. The use of blood agar containing gentamicin appears to offer a simple and inexpensive method for the recovery of S. pneumoniae and, in our opinion, provides an ideal method for the identification of pneumococcal carriers as well as for the recovery of these strains from clinical material such as sputum or ear exudates, where other and less fastidious organisms may also be present.

Agar

Sensitivity to penicillin of S. pneumoniae strains isolated from various pathological conditions.

297 S. pneumoniae strains isolated from patients with different pneumococcal infections during 1990-1991 were tested for the sensitivity to antibiotics--by the diffusimetric method to 9 antibiotics (Penicillin (6 micrograms), Ampicillin (10 micrograms), Erythromycin (15 micrograms), Oxacyllin (5 micrograms), Streptomycin (50 micrograms), Tetracycline (50 micrograms), Chloramphenicol (50 micrograms), Rifampicin (6 micrograms), and Kanamycin (30 micrograms) and by MIC determination to Penicillin and Erythromycin. 30% of S. pneumoniae strains were resistant to Penicillin and Erythromycin corresponding to a MIC > or = 1 UP/ml or > or = 1 microgram E/ml. The most active antibiotics were Chloramphenicol and Rifampicin and the less active: Tetracycline, Kanamycin and Streptomycin. A relation between the origin and serotype of the strains and the sensitivity to antibiotics was revealed. The strains from the throat, conjunctive and otic secretions and belonging to serotypes 19, 6 and 14 showed the highest levels of resistance to all antibiotics. A good correlation between MIC and diffusion method results was observed to Erythromycin and no correlation to Penicillin. In this last case the results of MIC determination to Penicillin were better correlated with the results of inhibitions diameters to Oxacyllin, method which have to be recommended.

Anti-Bacterial Agents