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BACTERIAL ANTIGEN CONCENTRATIONS IN CEREBROSPINAL FLUID AND PROGNOSIS OF PURULENT MENINGITIS
1361
Letters to the Editor BACTERIAL ANTIGEN CONCENTRATIONS IN CEREBROSPINAL FLUID AND PROGNOSIS OF PURULENT MENINGITIS
SIR,-Several studies, reviewed by Kaplan and Feigin,’ have shown that the concentration of bacterial capsular antigen in the CSF of patients with bacterial meningitis is related to the severity of the illness and to the prognosis. These studies have generally been done on small numbers of cases of meningococcal or Haemophilus influenzae meningitis. We have measured the antigen concentration, in CSF samples taken on admission, in 612 cases of purulent meningitis (90 meningococcal, 250 pneumococcal, and 272 H. influenzae meningitis) seen in 1977-80 at the Fann Hospital in Dakar, Senegal. A latex agglutination test was used. The latex particles were sensitised with monovalent antisera against H. influenzae b, Neisseria meningitis A and C (antisera from Bio Mérieux, Marcy I’Etoile, France), and the fourteen most frequent serotypes of Streptococcus pneumoniae encountered in Dakar (antisera from Statens Serum Institut, Copenhagen). The latex technique was the ’Slidex’ meningitis test (Bio Merieux), which is a variation of the Severin2 and Whittle3 techniques. The threshold concentration of antigen detection was determined for all of the fourteen sensitised latex preparations by the use of purified antigens. The antigen level in CSF samples was determined by successive two-fold dilutions; the highest dilution resulting in a visible agglutination with homologous latex multiplied by the threshold concentration, previously determined, gave the concentration of antigen in the
Microbiology and Infectious Diseases Department, Faculty of Medicine, Dakar, Senegal
F. DENIS M. CADOZ I. DIOP MAR
Bio Mérieux
Marcy l’Etoile, France
M. SAULNIER
PENICILLIN INDUCED HAEMOLYTIC ANAEMIA WITH NEGATIVE DIRECT ANTIGLOBULIN TEST
SIR,-Haemolytic anaemia is a rare complication of penicillin therapy. In reported cases the patient has usually been given large doses of penicillin (at least 10 megaunits daily),’ and the IgG direct antiglobulin (Coombs) test has always been strongly positive. I have seen penicillin induced haemolytic anaemia in a patient with repeatedly negative direct Coombs tests. A 69-year-old man who had had a right hemispheric cerebrovascular accident in 1974, with longstanding history of type 11 diabetes mellitus and essential hypertension, was seen in March, 1980, with cellulitis of the right great
toe. Culture of purulent revealed heavy growth of Staphylococcus aureus, and dicloxacillin 500 mg four times daily was prescribed. Although at first there was some improvement in the swelling and pain, on follow-up examination 2 weeks later a small area of gangrene had developed on the toe, and the patient was admitted on April 1, 1980, to Aultman Hospital. Repeat wound cultures revealed heavy growth of Staph. aureus. On the first hospital day the patient was started on nafcillin 2 g every 4 h intravenously. On hospital day 10 his right first toe was amputated, without complications. His haemoglobin (15’5 g/dl on admission) fell steadily, and by day 14 it was 9 -9 g/dl. At that point, nafcillin was discontinued. Direct Coombs tests on days 13 and 14 were negative. A stool specimen was negative for occult blood on day 13; a later specimen was reported as trace positive. Estimated blood loss during surgery was "minimal" and no major changes in hydration were observed. A glucose-6phosphate dehydrogenase screen was normal on day 16. Serum haptoglobin was 37 mg/dl on day 14 (normal 125-350 mg/dl). After discontinuation of nafcillin the haemoglobin concentration rose steadily and the reticulocyte count increased to a peak of 8 -1% on day 16. On day 17 the patient was started on folic acid 1 mg daily, which was continued until the time of discharge. Discharge haemoglobin was 12 -3g/dl. Because of poor healing of the amputation site, the patient was readmitted in July, 1980. The haemoglobin on hospital day 1 was 15-55 g/dl. On day 2 he underwent a lumbar sympathectomy and postoperatively was given intravenous ampicillin 1 g every 6 h. On day 5 his haemoglobin was 8-66 g/dl and ampicillin was discontinued. Thereafter his haemoglobin rose, and on discharge it was 11-1 1 g/dl despite no haematinic therapy or blood transfusion. Estimated blood loss during surgery was only 400 ml and stool was negative for occult blood on day 9. His reticulocyte count on day 7 was 6’ 7%. Wound healing improved postoperatively and he was discharged on day 9. Follow-up haemoglobin on Oct. 8, 1980, despite no further therapy, was 15-11 g/dl.
drainage
sample. The correlation between CSF antigen concentration and prognosis is summarised in the table. PROGNOSIS AND CSF ANTIGEN TITRE ON ADMISSION IN
612 CASES
OF
PURULENT MENINGITIS SEEN IN DAKAR
In
meningococcal meningitis the prognosis was not related to capsular antigen concentration in CSF. In H. influenzae meningitis there was a highly significant difference in the prognoses associated with high and low titres of
polyribose phosphate (PRP) in CSF: when the PRP level was less than 8 Mg/ml the case fatality rate was 16% and 61% of patients recovered completely, but of patients with PRP levels of 8 g/ml or more 50% died and only 32-5% recovered (p<0 000 1). Coonrod and Rytel4 found that patients with H. influenzae meningitis whose CSF had more than lg/ml of PRP were more likely to have a
subdural effusion than those whose CSF had less than that amount. Feigin and colleagues,,5 noted that the amount of PRP in the initial CSF sample was statistically related to the development of early and permanent sequelae; the incidence and severity of 1.
sequelae rose dramatically when the PRP concentration was above 1.28 pg/ml. For pneumococcal meningitis the critical CSF concentration of polysaccharidal antigen was 8 g/ml in our series, case fatality rates being 42-9% below and 68-5% above this concentration (p<0 000 I). In many cases in Africa the capsular antigen level will be above the highest level seen elsewhere, partly because the patient has been ill for a longer time before diagnosis. CSF antigen titres can be measured in less than half an hour,thus permitting more suitable treatment for patients with the poorest prognosis (highest titres).
Kaplan SL, Feigin RD. Rapid diagnosis of bacterial meningitis disease. In: Rytel MW, ed. Rapid diagnosis in infectious disease. Boca Raton, Florida: CRC Press, 1979: 105-13.
2. Severin WPJ. Latex agglutination in the diagnosis of meningococcal meningitis J Clin Pathol 1972; 25: 1079-82. 3. Whittle HC, Tugwell P, Egler J, Greenwood BM. Rapid bacteriological diagnosis of pyogenic meningitis by latex agglutination. Lancet 1974; ii. 619-21.
5.
1976; 88: 542-48 JI, Siber GR, Cheiffle DW, Smith DH. Rapid diagnosis of Haemophilus
6. Ward
4. Coonrod JD,
Rytel MW. Determination of aetiology of bacterial meningitis by counterimmunoelectrophoresis. Lancet 1972; i: 1154-57.
Feigin RD, Stechenberg BW, Chang MJ, Dunkle LM, Wong ML, Pakes H, Dodge PR, Davis H. Prospective treatment of Haemophilus influenzae meningitis J Pediatr
1.
influenzae type b infectious by latex particle agglutination and counterimmunoelectrophoresis. J Pediatr 1978; 93: 37-42. Garratty G, Petz LD. Drug induced hemolytic anemia. Am J Med 1975, 58: 398-407.
Letters to the Editor BACTERIAL ANTIGEN CONCENTRATIONS IN CEREBROSPINAL FLUID AND PROGNOSIS OF PURULENT MENINGITIS
SIR,-Several studies, reviewed by Kaplan and Feigin,’ have shown that the concentration of bacterial capsular antigen in the CSF of patients with bacterial meningitis is related to the severity of the illness and to the prognosis. These studies have generally been done on small numbers of cases of meningococcal or Haemophilus influenzae meningitis. We have measured the antigen concentration, in CSF samples taken on admission, in 612 cases of purulent meningitis (90 meningococcal, 250 pneumococcal, and 272 H. influenzae meningitis) seen in 1977-80 at the Fann Hospital in Dakar, Senegal. A latex agglutination test was used. The latex particles were sensitised with monovalent antisera against H. influenzae b, Neisseria meningitis A and C (antisera from Bio Mérieux, Marcy I’Etoile, France), and the fourteen most frequent serotypes of Streptococcus pneumoniae encountered in Dakar (antisera from Statens Serum Institut, Copenhagen). The latex technique was the ’Slidex’ meningitis test (Bio Merieux), which is a variation of the Severin2 and Whittle3 techniques. The threshold concentration of antigen detection was determined for all of the fourteen sensitised latex preparations by the use of purified antigens. The antigen level in CSF samples was determined by successive two-fold dilutions; the highest dilution resulting in a visible agglutination with homologous latex multiplied by the threshold concentration, previously determined, gave the concentration of antigen in the
Microbiology and Infectious Diseases Department, Faculty of Medicine, Dakar, Senegal
F. DENIS M. CADOZ I. DIOP MAR
Bio Mérieux
Marcy l’Etoile, France
M. SAULNIER
PENICILLIN INDUCED HAEMOLYTIC ANAEMIA WITH NEGATIVE DIRECT ANTIGLOBULIN TEST
SIR,-Haemolytic anaemia is a rare complication of penicillin therapy. In reported cases the patient has usually been given large doses of penicillin (at least 10 megaunits daily),’ and the IgG direct antiglobulin (Coombs) test has always been strongly positive. I have seen penicillin induced haemolytic anaemia in a patient with repeatedly negative direct Coombs tests. A 69-year-old man who had had a right hemispheric cerebrovascular accident in 1974, with longstanding history of type 11 diabetes mellitus and essential hypertension, was seen in March, 1980, with cellulitis of the right great
toe. Culture of purulent revealed heavy growth of Staphylococcus aureus, and dicloxacillin 500 mg four times daily was prescribed. Although at first there was some improvement in the swelling and pain, on follow-up examination 2 weeks later a small area of gangrene had developed on the toe, and the patient was admitted on April 1, 1980, to Aultman Hospital. Repeat wound cultures revealed heavy growth of Staph. aureus. On the first hospital day the patient was started on nafcillin 2 g every 4 h intravenously. On hospital day 10 his right first toe was amputated, without complications. His haemoglobin (15’5 g/dl on admission) fell steadily, and by day 14 it was 9 -9 g/dl. At that point, nafcillin was discontinued. Direct Coombs tests on days 13 and 14 were negative. A stool specimen was negative for occult blood on day 13; a later specimen was reported as trace positive. Estimated blood loss during surgery was "minimal" and no major changes in hydration were observed. A glucose-6phosphate dehydrogenase screen was normal on day 16. Serum haptoglobin was 37 mg/dl on day 14 (normal 125-350 mg/dl). After discontinuation of nafcillin the haemoglobin concentration rose steadily and the reticulocyte count increased to a peak of 8 -1% on day 16. On day 17 the patient was started on folic acid 1 mg daily, which was continued until the time of discharge. Discharge haemoglobin was 12 -3g/dl. Because of poor healing of the amputation site, the patient was readmitted in July, 1980. The haemoglobin on hospital day 1 was 15-55 g/dl. On day 2 he underwent a lumbar sympathectomy and postoperatively was given intravenous ampicillin 1 g every 6 h. On day 5 his haemoglobin was 8-66 g/dl and ampicillin was discontinued. Thereafter his haemoglobin rose, and on discharge it was 11-1 1 g/dl despite no haematinic therapy or blood transfusion. Estimated blood loss during surgery was only 400 ml and stool was negative for occult blood on day 9. His reticulocyte count on day 7 was 6’ 7%. Wound healing improved postoperatively and he was discharged on day 9. Follow-up haemoglobin on Oct. 8, 1980, despite no further therapy, was 15-11 g/dl.
drainage
sample. The correlation between CSF antigen concentration and prognosis is summarised in the table. PROGNOSIS AND CSF ANTIGEN TITRE ON ADMISSION IN
612 CASES
OF
PURULENT MENINGITIS SEEN IN DAKAR
In
meningococcal meningitis the prognosis was not related to capsular antigen concentration in CSF. In H. influenzae meningitis there was a highly significant difference in the prognoses associated with high and low titres of
polyribose phosphate (PRP) in CSF: when the PRP level was less than 8 Mg/ml the case fatality rate was 16% and 61% of patients recovered completely, but of patients with PRP levels of 8 g/ml or more 50% died and only 32-5% recovered (p<0 000 1). Coonrod and Rytel4 found that patients with H. influenzae meningitis whose CSF had more than lg/ml of PRP were more likely to have a
subdural effusion than those whose CSF had less than that amount. Feigin and colleagues,,5 noted that the amount of PRP in the initial CSF sample was statistically related to the development of early and permanent sequelae; the incidence and severity of 1.
sequelae rose dramatically when the PRP concentration was above 1.28 pg/ml. For pneumococcal meningitis the critical CSF concentration of polysaccharidal antigen was 8 g/ml in our series, case fatality rates being 42-9% below and 68-5% above this concentration (p<0 000 I). In many cases in Africa the capsular antigen level will be above the highest level seen elsewhere, partly because the patient has been ill for a longer time before diagnosis. CSF antigen titres can be measured in less than half an hour,thus permitting more suitable treatment for patients with the poorest prognosis (highest titres).
Kaplan SL, Feigin RD. Rapid diagnosis of bacterial meningitis disease. In: Rytel MW, ed. Rapid diagnosis in infectious disease. Boca Raton, Florida: CRC Press, 1979: 105-13.
2. Severin WPJ. Latex agglutination in the diagnosis of meningococcal meningitis J Clin Pathol 1972; 25: 1079-82. 3. Whittle HC, Tugwell P, Egler J, Greenwood BM. Rapid bacteriological diagnosis of pyogenic meningitis by latex agglutination. Lancet 1974; ii. 619-21.
5.
1976; 88: 542-48 JI, Siber GR, Cheiffle DW, Smith DH. Rapid diagnosis of Haemophilus
6. Ward
4. Coonrod JD,
Rytel MW. Determination of aetiology of bacterial meningitis by counterimmunoelectrophoresis. Lancet 1972; i: 1154-57.
Feigin RD, Stechenberg BW, Chang MJ, Dunkle LM, Wong ML, Pakes H, Dodge PR, Davis H. Prospective treatment of Haemophilus influenzae meningitis J Pediatr
1.
influenzae type b infectious by latex particle agglutination and counterimmunoelectrophoresis. J Pediatr 1978; 93: 37-42. Garratty G, Petz LD. Drug induced hemolytic anemia. Am J Med 1975, 58: 398-407.