Safety and immunogenicity of two Salmonella typhi Vi capsular polysaccharide vaccines.
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Biomedical subjects
Publications and source records attributed to M Cadoz.
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On day 0, four groups of children (3 to 6 months old) randomly received IPV alone or IPV + pertussis, or IPV + DP, or IPV + DTP. At days 28 and 56, all the children received the same IPV + DTP vaccine. Polio neutralizing and diphtheria antibodies were determined at days 0, 28 and 56. No adjuvant and even some inhibitory effect of pertussis was observed at days 28 and 56 on mean polio antibody titers. These results are compared to those observed with diphtheria.
A 23 valent pneumococcal vaccine containing 25 micrograms of each polysaccharide was administered to 30 healthy adults. Adverse reactions were always mild, consisting only of local pain and erythema in most subjects. Pre- and four weeks post-vaccination sera were analysed by radioimmunoassay. Geometric mean titre (GMT) ratios were between 2.3 and 14.3 (overall mean X 5.7) according to type. A level of 300 ng of antibody N/ml, the supposedly protective level, was achieved in at least 86.6% of the subjects for all the serotypes.
Tetravalent meningococcal polysaccharide vaccine (groups A, C, Y and W 135) was administered (s.c.) to 26 healthy children, aged three to 13 years old, in order to assess safety and immunogenicity of the vaccine. Side effects were very mild in all children, generally consisting of local soreness for a few hours following injection. A fourfold increase in bactericidal antibody titres was obtained for the four components in 100% of initially seronegative children. This vaccine thus appears as safe and immunogenic in children as it is in adults.
Haemophilus influenzae meningitis are frequent in Africa in infants between 6 months and two years of age. Type b is observed in 97% of cases. In Dakar, 2% of strains are resistant to ampicillin and 0% to chloramphenicol. Lethality is about 30% and sequellae are very frequent. Prognosis can be predicted by a cotation scale including consciousness, tonus, seizures, nutritional status, delay before treatment and initial bacterial antigen level in CSF.
Authors have searched for Haemophilus influenzae by culture and by detection of capsular antigens in CSF of 1.700 bacterial meningitis in Dakar. Culture has been positive in 71.9%, counter-immunoelectrophoresis in 94.9% and latex (slidex meningitis kit) in 91.2% of cases. Diagnosis results are improved of 39% comparatively with bacteriologic culture. False positive results caused by antigenic cross-reactions have been observed only in 1.3% of others bacterial meningitis. Latex-test is allowing a diagnosis in three minutes and a quantitative determination of antigens (useful for pronostic).
Hundred and fifteen children suffering of purulent meningitis (S.pneumoniae: 19; H.influenzae: 44; N.meningitidis; 23; others: 29) were treated by amoxicillin 200 mg/kg/day in four intramuscular injections. Spinal taps for assay of antibiotic levels in the CSF were taken 1 or 3 or 6 hours after the injection. The levels were respectively for this samples of 6.9 -1.7-1.4 micrograms/ml during the first 48 hours of treatment and 4.4-1.7-1.9 after one week. The concentrations CSF/serum were from 5 to 9.8 per cent at the beginning of treatment.
Two series of patients suffering purulent meningitis were treated: one (137 patients) with amoxycillin (200 mg/kg/day) by 4 intramuscular injections each day, the other with ceftriaxone (163 patients)/42 mg/Kg/day IM by intramuscular injections each day in the first 23 patients and then only one injection by day in the 140 other patients. Bacteriologically the superiority of CFTRX appears the whole studied strains: MIC of CFTRX are four times lower than those of AMOX for pneumococci, ten times lower for H. influenzae, hundred time lower for meningococci. Amongst the add strains the percentage of resistance to AMOX reaches 64 and only 7 to CFTRX. Pharmacologically, after a same dose of 50mg/kg the peak concentrations in CSF has the same level: CFTRX: 6.8 micrograms/ml, AMOX: 6 micrograms/ml. CSF levels remain efficient for 2 hours with AMOX and for 24 hours with CFTRX. The therapeutic index (mean antibiotic concentration in CSF/mean MIC of the strains) is higher with CFTRX than with AMOX (X 4 for pneumococci, X 15 for H. influenzae, X 100 for meningococci). Clinical results are better with CFTRX than with AMOX in each of the aetiological groups except meningococcal meningitis but the only significative difference concerns pneumococcal meningitis. Clinical tolerance of the two treatments was good. However 2 neonates treated with CFTRX has a severe eczematous erythrodermia and 8 other patients treated with CFTRX had diarrhoea due to elimination of the sensitive flora.
The cerebrospinal fluids of 920 Senegalese patients with purulent meningitis wee examined by latex particle agglutination (LA) and the results were compared with those of conventional bacteriology and of counter immuno electro phoresis (C.I.E.). For all three organisms taken globally, CSF culture was positive in 72.7% of the patients, the LA test in 78.8% and the C.I.E. test in 89.0%. The LA test was positive in 17.9% of subjects with negative CSF culture. When the results wee analysed for each organism separately, the LA test was positive in 69.3%, 74.7% and 85.9% respectively of patients with meningococcal, pneumococcal and H. influenzae b meningitis. False agglutinations were found in 6.7% of meningitis due to other pathogens. Cross-reactions and autoagglutinations were rare (0.4% and 3.7% respectively). The sensitivity, specificity, simplicity and rapidity of the LA test make it extremely useful for the diagnosis of purulent meningitis, particularly in Africa.
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In 21 of the 24 cases the diagnosis of purulent meningitis was confirmed by culturing the causal agent and/or by immunological diagnosis. The daily dosage of Rocephin ranged between 15 and 200 mg/kg administered in 2 i.m. injections. A cure was achieved in cases of meningococcal meningitis (1 case with sequelae: blindness in one eye), in 5 out of 6 cases of Haemophilus influenzae meningitis (1 case with severe neuropsychiatric sequelae), in 3 out of 9 cases of pneumococcal meningitis and in 2 out of 4 cases of enterobacterial meningitis. The tolerance was generally excellent. Sterilisation of the cerebrospinal fluid (CSF) was achieved in all 20 cases of meningitis confirmed by culture. The MIC levels are lower than the lowest CSF peak for Rocephin found in this study. The unusual pharmacological behavior of Rocephin makes it possible to achieve and to maintain for a long time highly satisfactory concentration levels in the CSF. These properties of Rocephin should lift the long-standing objections to the use of cephalosporins for the treatment of purulent meningitis.
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Over a period of 5 years (1973--1977), 1083 patients were hospitalised in the Infectious Disease Clinic of the Dakar University Hospital Centre with bacteriologically confirmed purulent meningitis. The pneumococcus was responsible in 462 cases (42.6%). Analysis of 402 records showed that 234 patients (58.2% of cases) died, 123 were completely cured (30.6%) whilst there were neurological sequelae in 45 cases (28% of the survivors). The chief factors in poor prognosis were the existence and depth of changes in conscious level, age over 20 years, a CSF cell count of less than 500 per mm3, a CSF protein level greater than 2 g per 1 and I CSF antigen level over 8 microgram per ml. From a therapeutic standpoint, the percentage mortality was similar with chloramphenicol and with penicillin G, but complete cures were statistically more frequent in the patients treated initially with chloramphenicol.
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Pneumococcal meningitis, because of their frequency and their severity, are regarded as an important problem of Public Health in Africa. In a great number of African countries, particularly Equatorial and Central Africa, the pneumococcus is the first agent of bacterial meningitis. The annual prevalence is estimated as about 14/100 000 persons. The case fatality rate (on 1 600 cases) is 49,5% ; the annual mortality reaches about 7/100 000 (28 000 annual deaths in Africa). The babies and the old persons are more exposed to the risk, with an annual prevalence of 28,5/100 000 before five years old, and of 16,1/100 000 after sixty years old. The risk is small between five and forty five years old. The risk is very high in patients homozygous for sickle-cell disease. The spread of all detected serotypes, by descending frequency is : 1, 5, 6, 3, 23, 12, 2, 14, 9, 18, 19, 4, 8, 29, 40, others (Danish system of nomenclature). The distribution according to age is indicated by the authors. A vaccine with only 8 serotypes (1, 5, 6, 3, 23, 12, 2, 14) could cover 80% of serotypes in Dakar. For the babies, addition to pneumococcal vaccine with polyribose phosphate of Haemophilus influenzae b, could be useful, because high prevalence of meningitis with this germ before five years old in Africa.
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