Hospital Practice
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
The Challenge of Bacterial Meningitis David H. Smith To cite this article: David H. Smith (1976) The Challenge of Bacterial Meningitis, Hospital Practice, 11:6, 71-80, DOI: 10.1080/21548331.1976.11706951 To link to this article: http://dx.doi.org/10.1080/21548331.1976.11706951
Published online: 06 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [FU Berlin]
Date: 27 November 2016, At: 21:18
cAm
------------------------------------------------------~----
The Challenge of Bacterial Meningitis DAVID B. SMITil
Harvard Medical School
Acute CNS infection, often originating in the otonasopharyngeal structures, remains a major problem in children with respect to frequency and severity of consequences. Optimal chemotherapy is outlined.
In frequency and severity of consequences, bacterial meningitis equals or exceeds several other diseases of children for which active immunization is now practiced. For despite the availability of specific therapy, acute CNS infection arising from bacterial invasion of the meninges remains a life-threatening disease among young children, and among survivors neurologic sequelae arc common and severe. Prompt diagnosis and management has a favorable influence on both immediate and long-term prognosis. Thus physicians caring for children must anticipate the possibility of this diagnosis when findings arc suggestive, and intervene without delay. Until recently, reliable data on incidence were lacking, partly because bacterial meningitis as such is not a reportable disease. However, several community surveys involving large and well-defined populations have helped to fill the gap, indicating an annual attack rate of about 1/2,000 in the five-and-younger age group. In some situations, also, the attack rate of bacterial meningitis has been found to be considerably higher than 1/2,000. For example, a survey in Charleston, S.C., recorded an annual incidence of 3.6/l,ooo for meningitis due to Haemophilus influenzae alone in children from the poorest socioeconomic stratum. This survey also confirmed the role of sickle-cell disease as an added risk factor in pneumococcal meningitis. Thus in black children the attack rate for pneumococcal meningitis was 36 times higher if sickle-cell disease was present. When racial groups were compared in another study, incidence was 314 times higher in black children with sickle-cell disease than in white children who lived in otherwise similar social circumstances. In addition, there is evi-
dcncc that sickle-cell disease also predisposes its victims to H. influenzae meningitis.
Etiology of Meningitis Nearly all bacterial meningitis beyond the neonatal period is caused by one of three organisms: H. influenzae, pneumococci, and meningococci. Mixed bacterial infections are rare, as is the combination of bacterial and viral meningitis. A more important fact is that H. influenzae meningitis clearly predominates among the three bacterial types, causing about 6o% of all cases. Wherever the question has been studied, the occurrence of influenza! meningitis has been found to be rising. Consider the fact that admissions of patients with H. influenzae meningitis at the Children's Hospital of Pittsburgh increased by more than 400% over arecent 25-ycar period; during the same time span, total hospital admissions increased by so%. At the Columbus (Ohio) Children's Hospital, the number of children admitted with H. influenzae meningitis increased by 399% between study period A (1942-50) and study period C (190%
Glucose
50-90 mg/100 ml
30mgl100ml
Protein
20-40 mg/100 ml
450 mg/100 ml
Lactate
0.8-2.4 mg/100 ml
105 mg/100 ml
Lactic dehydrogenase activity
sou
Glutamic oxaloacetic transaminase activity
10.8U
251
u
49.7U
•At onset of disease
Jarvis and Saxena (1972) Winkelstein (1971) Positive Culture Partially Treated
Untreated
Antibiotic therapy prior to lumbar tap may so modify CSF 1wrameters as to confuse the diagnosis, according to study by Jarvis and Saxena; however, Winkel stein found that partial treatment had minimal effect.
Hospital Practin: Junl/ 1976
77
Acute Complications of Bacterial Meningitis Therapy
Complication
Septic shock
Plasma volume replacement, oxygen,? isoproterenol, digitalization, corticosteroids
Brain edema
Mannitol, glycerol, dexamethasone
Hyponatremia
limit fluid intake, carefully watch electrolyte balance
Disseminated intravascular coagulation
? Heparin
Convulsions
Variable with mechanism
Myocarditis
Digitalization
by Haggerty et al at our hospital, using high-dose methylprednisolone; another by Belsey et al in New Orleans, using low-dose dexamethasone). Steroids are probably indicated in the presence of shock, since these children may be steroid-depleted; their proposed inotropic effect may also be of use in the treatment of shock. Seizures occur in about 30% of the cases and must be appropriately managed; over-medication is to be avoided. As a rule, seizures of short duration and low frequency are not clinically serious. On the other hand, recurrent and prolonged seizures involving different foci may be difficult to control despite medication. Focal recurrent seizures may be associated with subdural effusion. A first consideration in treating seizures is to maintain a clear airway, with supplemental oxygen and suction as necessary. Blood pressure must be maintained and any respiratory acidosis corrected. Several drugs are of immediate value: diphenylhydantoin, phenobarbital, diazepam. But diphenylhydantoin in large doses can produce hypotension, and the repeated combination of diazepam and phenobarbital may precipitate respiratory depression; short-acting barbiturates are contraindicated for the same reason. Long-term anticonvulsants may be needed if clinical seizures persist and the EEGs continue to show seizure discharges.
Complications
Subdural tap to relieve significant effusion is perfotmed
by inserting needle near the junction of the fontanel ancl coronal suture; repeated tapping is needed in some instances to control this complication.
78
Hospital Practice June 1976
If looked for assiduously, subdural effusion is detectable in a very high proportion of cases; in some series, up to so% of the children have been affected. Symptoms such as lethargy, unsatisfactory clinical improvement, increasing head size, or focal recurrent seizures should suggest the diagnosis. Fever is not a reliable sign. The diagnosis can be confirmed by transillumination, computerized axial tomography (CAT) scans, and direct subdural tap. Unfortunately, significant subdural effusion most often occurs during infancy, when there may be only vague clues. The physician should certainly consider the possibility if an infant seems unusually sick for the first few days and is still not well after the fourth to eighth day. Transillumination of the skull should be performed without delay, followed by subdural tapping if indicated. Treatment consists of removing 15 to 20 ml of fluid at a time by repeated tapping, daily if necessary. One caution, however, should be noted: repeated subdural tapping of small volumes of fluid may actually in-
----------------------------------~~-duce fluid collection. Thus, therapeutic subdural taps are not recommended for small collections of fluid. Early surgical intervention as formerly practiced seldom seems necessary. However, a neurosur-
geon should be consulted if large volumes of fluid persist for two weeks despite tapping, since a surgical procedure may be required to eliminate the problem. As with other acute complications, the frequency of subdural effusion is highest in children with H. influenzae meningitis, and it is lowest in those with meningococcal meningitis.
Spread of Infection In meningococcal meningitis there is at least a 1% risk that siblings of an affected child will also develop
the disease. More than half of these secondary cases become symptomatic within two to three days following the onset of the primary case. Prophylactic antibiotic therapy can reduce or eliminate this risk. The question of who should receive such therapy is controversial. The risk to professional personnel or casual contacts, such as schoolmates, is extremely small; it is greatest among family members with intimate contact, particularly young children. We therefore recommend that prophylactic antibiotic therapy be given only to such family members. Because of the cited time course of secondary cases, this decision must be made as soon as the diagnosis of the primary case is confirmed. In the past, prophylaxis was accomplished with three days of oral sulfonamide therapy; this treatment
Therapy of Bacterial Meningitis Antibacterial Therapy
Indications
Antibiotic
Dosage Schedule
Route
Ampicillin
Haemophilus inffuenzae, if sensitive; bacterial meningitis of unkown origin; alternate antibiotic for meningococcal, pneumococcal meningitis
75 mg/kg q6hr
IV
Chloramphenicol
H. influenzae, particularly if resistant to ampicillin; bacterial meningitis of unknown origin; alternate antibiotic for meningococcal, pneumococcal meningitis, particularly if patient has penicillin allergy
25 mg/kg q6 hr
IV
Crystalline penicillin G
Pneumococcal, meningococcal meningitis
60,000 U/kg q4hr
IV
Convul~ions•
Anticonvulsant
Dosage Schedule
Indications
Route
Diazepam
Acute convulsions
1 mg/kg/yr of age to a maximum of 10 mg, given over 1-2 min
Paraldehyde
Acute convulsions
0.3 mil/kg (maximum 10 ml)
Acute convulsions
6-10 mg/kg, given over 30 min (less than 25 mglmin, less than 1 gm/dose)
Maintenance
6 mg/kg/day
Acute convulsions
5mg/kg
Maintenance
5/mg/kg/day
Diphenylhydantoin Phenobarbital
IV Per rectum IV PO,IM IM or 1/2 dose IM, 1/2 dose IV PO,IM
Cerebral Edema •
Drug
Indications
Dexamethasone
Unconscious patient with abnormal pupillary reflexes hypertension, decerbrate rigidity, signs of herniation
Mannitol
As above; rebound may be observed; urine output should be monitored
Glycerol
As above; effect not so rapid as with mannitol
Dosage Schedule
Route
2-4 mg/stat 1-2mgq6hr
IV
1.5-2 gm/kg over 10-20 min
IV
1-2 gm/kg q6hr
Per nasogastric tube
•Temperature control, qxygen; prevention of acidosis, overhydration, and hyponatremia- important therapy for convulsions and cerebral edema
Hospital Practice June 1Q76
79
------~~------------------------------------------------------------------------eliminated nasopharyngeal infection and prevented secondary cases of meningitis. At present, however, at least one half of meningococci isolated in this country arc sulfonamide-resistant. Only two other antibiotics effectively eradicate meningococcal colonization of the nasopharynx: rifampin and minocyclinc. Recent reports of toxicity preclude our recommendation of the latter drug; we therefore employ three days of oral rifampin therapy. To prevent secondary cases that may develop days to weeks after the primary case, immunization with a meningococcal vaccine is recommended by some. Unfortunately, vaccines are available for only types A and C meningococci, and efficacy has been proved only in individuals of six years and older. The likelihood of a second case of H. in~uenzae type b meningitis in a family seemed remote until the question was explored. When we studied it, we were surprised to find multiple infections in 3% of the families, a substantial risk indeed. Unfortunately, short-term therapy as used in meningococcal prophylaxis generally docs not eliminate nasopharyngeal colonization with H. influenzae and presumably therefore will not prevent secondary cases. Thus, the physician must keep on the alert and in close touch with the family; if a second child is to become ill, it
will probably be within 48 hours. Immunization Against Meningitis At the opening of this article, I noted that bacterial meningitis is a pediatric problem at least equal in significance to that of many diseases for which immunization is now practiced. How close are we to being able to induce immunity against bacterial menin-
Selected Reading Smith DH et al: Bacterial meningitis: a symposium. Pediatrics 52:586, 1973 Converse GM e. al: Alteration of cerebrospinal fluid findings by partial treatment of bacterial meningitis. J Pediatr 83:220, 1973
Fraser DW et al: Risk factors in bacterial meningitis: Charlestown County, South Carolina. J Infect Dis 127:271, 1973 Sell SHW et al: Long-term sequelae of Haemophilus influenzae meningitis. Pediatrics 49:2o6, 1972 O'Reilly RJ et al: Circulating polyribophosphate in Haemophilus influenzae type b meningitis: correlation with clinical course and antibody response. J Clin Invest 56:1012, 1975 Smith EWP, Haynes RE: Changing incidence of Haemoph-
ilus influenzae meningitis. Pediatrics 50:723, 1972
Ho
Hospital Practit·c June 1976
gitis in early childhood? This is clearly of great practical import to pediatricians and family doctors. The recently licensed vaccines specific for types A and C meningococci arc being introduced primarily for adult populations at high risk. Children older than six years may also benefit, but efficacy has not been documented with younger children. Moreover, preparations similarly derived for type B meningococci are ineffective at any age, for reasons unknown, and, as noted earlier, most cases of meningococcal meningitis arc caused by type B and type C organisms. The meningococcal vaccines are the purified polysaccharide capsular antigen. We have been working with an H. in~uenzae type b vaccine prepared from purified PRP. After this vaccine was shown to be nontoxic and immunogenic in adults, we began tests in infants and young children. Immunizations are well tolerated, and a single injection triggers a significant antibody response in up to 95% of individuals older than two years. On the basis of this type of study, large-scale efficacy trials arc now under way in this country and abroad (in Finland). Preliminary results have been both promising and discouraging. It appears that the vaccine is highly effective in children older than two years but is not effective in younger children. The problem, of course, is that about 70% of all cases of H. influenzae meningitis occur in children younger than two years. Of the several possible alternative approaches, one is to make the bacterial antigen more complex (combining polysaccharide and protein). Studies have been initiated with such a preparation; the results are encouraging and the work is continuing. An alternative approach (being pursued by Robbins and colleagues) derives from the observation that certain Escherichia coli strains possess antigens cross-reactive with PRP; conceivably, feeding of one of these apparently innocuous strains could induce immunity against H. in~uenzaediscase. Pneumococcal vaccines are being tested for prevention of otitis media; the prevention of pneumococcal meningitis is not being evaluated. For the present, then, physicians in practice should be kept informed of ongoing programs to achieve safe and effective immunity in the age groups most vulnerable to bacterial meningitis. Their immediate focus, however, must be on ensuring early diagnosis and prompt therapy, including necessary supportive care - which are critical to the survival of healthy children affected with acute bacterial meningitis. D
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
The Challenge of Bacterial Meningitis David H. Smith To cite this article: David H. Smith (1976) The Challenge of Bacterial Meningitis, Hospital Practice, 11:6, 71-80, DOI: 10.1080/21548331.1976.11706951 To link to this article: http://dx.doi.org/10.1080/21548331.1976.11706951
Published online: 06 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [FU Berlin]
Date: 27 November 2016, At: 21:18
cAm
------------------------------------------------------~----
The Challenge of Bacterial Meningitis DAVID B. SMITil
Harvard Medical School
Acute CNS infection, often originating in the otonasopharyngeal structures, remains a major problem in children with respect to frequency and severity of consequences. Optimal chemotherapy is outlined.
In frequency and severity of consequences, bacterial meningitis equals or exceeds several other diseases of children for which active immunization is now practiced. For despite the availability of specific therapy, acute CNS infection arising from bacterial invasion of the meninges remains a life-threatening disease among young children, and among survivors neurologic sequelae arc common and severe. Prompt diagnosis and management has a favorable influence on both immediate and long-term prognosis. Thus physicians caring for children must anticipate the possibility of this diagnosis when findings arc suggestive, and intervene without delay. Until recently, reliable data on incidence were lacking, partly because bacterial meningitis as such is not a reportable disease. However, several community surveys involving large and well-defined populations have helped to fill the gap, indicating an annual attack rate of about 1/2,000 in the five-and-younger age group. In some situations, also, the attack rate of bacterial meningitis has been found to be considerably higher than 1/2,000. For example, a survey in Charleston, S.C., recorded an annual incidence of 3.6/l,ooo for meningitis due to Haemophilus influenzae alone in children from the poorest socioeconomic stratum. This survey also confirmed the role of sickle-cell disease as an added risk factor in pneumococcal meningitis. Thus in black children the attack rate for pneumococcal meningitis was 36 times higher if sickle-cell disease was present. When racial groups were compared in another study, incidence was 314 times higher in black children with sickle-cell disease than in white children who lived in otherwise similar social circumstances. In addition, there is evi-
dcncc that sickle-cell disease also predisposes its victims to H. influenzae meningitis.
Etiology of Meningitis Nearly all bacterial meningitis beyond the neonatal period is caused by one of three organisms: H. influenzae, pneumococci, and meningococci. Mixed bacterial infections are rare, as is the combination of bacterial and viral meningitis. A more important fact is that H. influenzae meningitis clearly predominates among the three bacterial types, causing about 6o% of all cases. Wherever the question has been studied, the occurrence of influenza! meningitis has been found to be rising. Consider the fact that admissions of patients with H. influenzae meningitis at the Children's Hospital of Pittsburgh increased by more than 400% over arecent 25-ycar period; during the same time span, total hospital admissions increased by so%. At the Columbus (Ohio) Children's Hospital, the number of children admitted with H. influenzae meningitis increased by 399% between study period A (1942-50) and study period C (190%
Glucose
50-90 mg/100 ml
30mgl100ml
Protein
20-40 mg/100 ml
450 mg/100 ml
Lactate
0.8-2.4 mg/100 ml
105 mg/100 ml
Lactic dehydrogenase activity
sou
Glutamic oxaloacetic transaminase activity
10.8U
251
u
49.7U
•At onset of disease
Jarvis and Saxena (1972) Winkelstein (1971) Positive Culture Partially Treated
Untreated
Antibiotic therapy prior to lumbar tap may so modify CSF 1wrameters as to confuse the diagnosis, according to study by Jarvis and Saxena; however, Winkel stein found that partial treatment had minimal effect.
Hospital Practin: Junl/ 1976
77
Acute Complications of Bacterial Meningitis Therapy
Complication
Septic shock
Plasma volume replacement, oxygen,? isoproterenol, digitalization, corticosteroids
Brain edema
Mannitol, glycerol, dexamethasone
Hyponatremia
limit fluid intake, carefully watch electrolyte balance
Disseminated intravascular coagulation
? Heparin
Convulsions
Variable with mechanism
Myocarditis
Digitalization
by Haggerty et al at our hospital, using high-dose methylprednisolone; another by Belsey et al in New Orleans, using low-dose dexamethasone). Steroids are probably indicated in the presence of shock, since these children may be steroid-depleted; their proposed inotropic effect may also be of use in the treatment of shock. Seizures occur in about 30% of the cases and must be appropriately managed; over-medication is to be avoided. As a rule, seizures of short duration and low frequency are not clinically serious. On the other hand, recurrent and prolonged seizures involving different foci may be difficult to control despite medication. Focal recurrent seizures may be associated with subdural effusion. A first consideration in treating seizures is to maintain a clear airway, with supplemental oxygen and suction as necessary. Blood pressure must be maintained and any respiratory acidosis corrected. Several drugs are of immediate value: diphenylhydantoin, phenobarbital, diazepam. But diphenylhydantoin in large doses can produce hypotension, and the repeated combination of diazepam and phenobarbital may precipitate respiratory depression; short-acting barbiturates are contraindicated for the same reason. Long-term anticonvulsants may be needed if clinical seizures persist and the EEGs continue to show seizure discharges.
Complications
Subdural tap to relieve significant effusion is perfotmed
by inserting needle near the junction of the fontanel ancl coronal suture; repeated tapping is needed in some instances to control this complication.
78
Hospital Practice June 1976
If looked for assiduously, subdural effusion is detectable in a very high proportion of cases; in some series, up to so% of the children have been affected. Symptoms such as lethargy, unsatisfactory clinical improvement, increasing head size, or focal recurrent seizures should suggest the diagnosis. Fever is not a reliable sign. The diagnosis can be confirmed by transillumination, computerized axial tomography (CAT) scans, and direct subdural tap. Unfortunately, significant subdural effusion most often occurs during infancy, when there may be only vague clues. The physician should certainly consider the possibility if an infant seems unusually sick for the first few days and is still not well after the fourth to eighth day. Transillumination of the skull should be performed without delay, followed by subdural tapping if indicated. Treatment consists of removing 15 to 20 ml of fluid at a time by repeated tapping, daily if necessary. One caution, however, should be noted: repeated subdural tapping of small volumes of fluid may actually in-
----------------------------------~~-duce fluid collection. Thus, therapeutic subdural taps are not recommended for small collections of fluid. Early surgical intervention as formerly practiced seldom seems necessary. However, a neurosur-
geon should be consulted if large volumes of fluid persist for two weeks despite tapping, since a surgical procedure may be required to eliminate the problem. As with other acute complications, the frequency of subdural effusion is highest in children with H. influenzae meningitis, and it is lowest in those with meningococcal meningitis.
Spread of Infection In meningococcal meningitis there is at least a 1% risk that siblings of an affected child will also develop
the disease. More than half of these secondary cases become symptomatic within two to three days following the onset of the primary case. Prophylactic antibiotic therapy can reduce or eliminate this risk. The question of who should receive such therapy is controversial. The risk to professional personnel or casual contacts, such as schoolmates, is extremely small; it is greatest among family members with intimate contact, particularly young children. We therefore recommend that prophylactic antibiotic therapy be given only to such family members. Because of the cited time course of secondary cases, this decision must be made as soon as the diagnosis of the primary case is confirmed. In the past, prophylaxis was accomplished with three days of oral sulfonamide therapy; this treatment
Therapy of Bacterial Meningitis Antibacterial Therapy
Indications
Antibiotic
Dosage Schedule
Route
Ampicillin
Haemophilus inffuenzae, if sensitive; bacterial meningitis of unkown origin; alternate antibiotic for meningococcal, pneumococcal meningitis
75 mg/kg q6hr
IV
Chloramphenicol
H. influenzae, particularly if resistant to ampicillin; bacterial meningitis of unknown origin; alternate antibiotic for meningococcal, pneumococcal meningitis, particularly if patient has penicillin allergy
25 mg/kg q6 hr
IV
Crystalline penicillin G
Pneumococcal, meningococcal meningitis
60,000 U/kg q4hr
IV
Convul~ions•
Anticonvulsant
Dosage Schedule
Indications
Route
Diazepam
Acute convulsions
1 mg/kg/yr of age to a maximum of 10 mg, given over 1-2 min
Paraldehyde
Acute convulsions
0.3 mil/kg (maximum 10 ml)
Acute convulsions
6-10 mg/kg, given over 30 min (less than 25 mglmin, less than 1 gm/dose)
Maintenance
6 mg/kg/day
Acute convulsions
5mg/kg
Maintenance
5/mg/kg/day
Diphenylhydantoin Phenobarbital
IV Per rectum IV PO,IM IM or 1/2 dose IM, 1/2 dose IV PO,IM
Cerebral Edema •
Drug
Indications
Dexamethasone
Unconscious patient with abnormal pupillary reflexes hypertension, decerbrate rigidity, signs of herniation
Mannitol
As above; rebound may be observed; urine output should be monitored
Glycerol
As above; effect not so rapid as with mannitol
Dosage Schedule
Route
2-4 mg/stat 1-2mgq6hr
IV
1.5-2 gm/kg over 10-20 min
IV
1-2 gm/kg q6hr
Per nasogastric tube
•Temperature control, qxygen; prevention of acidosis, overhydration, and hyponatremia- important therapy for convulsions and cerebral edema
Hospital Practice June 1Q76
79
------~~------------------------------------------------------------------------eliminated nasopharyngeal infection and prevented secondary cases of meningitis. At present, however, at least one half of meningococci isolated in this country arc sulfonamide-resistant. Only two other antibiotics effectively eradicate meningococcal colonization of the nasopharynx: rifampin and minocyclinc. Recent reports of toxicity preclude our recommendation of the latter drug; we therefore employ three days of oral rifampin therapy. To prevent secondary cases that may develop days to weeks after the primary case, immunization with a meningococcal vaccine is recommended by some. Unfortunately, vaccines are available for only types A and C meningococci, and efficacy has been proved only in individuals of six years and older. The likelihood of a second case of H. in~uenzae type b meningitis in a family seemed remote until the question was explored. When we studied it, we were surprised to find multiple infections in 3% of the families, a substantial risk indeed. Unfortunately, short-term therapy as used in meningococcal prophylaxis generally docs not eliminate nasopharyngeal colonization with H. influenzae and presumably therefore will not prevent secondary cases. Thus, the physician must keep on the alert and in close touch with the family; if a second child is to become ill, it
will probably be within 48 hours. Immunization Against Meningitis At the opening of this article, I noted that bacterial meningitis is a pediatric problem at least equal in significance to that of many diseases for which immunization is now practiced. How close are we to being able to induce immunity against bacterial menin-
Selected Reading Smith DH et al: Bacterial meningitis: a symposium. Pediatrics 52:586, 1973 Converse GM e. al: Alteration of cerebrospinal fluid findings by partial treatment of bacterial meningitis. J Pediatr 83:220, 1973
Fraser DW et al: Risk factors in bacterial meningitis: Charlestown County, South Carolina. J Infect Dis 127:271, 1973 Sell SHW et al: Long-term sequelae of Haemophilus influenzae meningitis. Pediatrics 49:2o6, 1972 O'Reilly RJ et al: Circulating polyribophosphate in Haemophilus influenzae type b meningitis: correlation with clinical course and antibody response. J Clin Invest 56:1012, 1975 Smith EWP, Haynes RE: Changing incidence of Haemoph-
ilus influenzae meningitis. Pediatrics 50:723, 1972
Ho
Hospital Practit·c June 1976
gitis in early childhood? This is clearly of great practical import to pediatricians and family doctors. The recently licensed vaccines specific for types A and C meningococci arc being introduced primarily for adult populations at high risk. Children older than six years may also benefit, but efficacy has not been documented with younger children. Moreover, preparations similarly derived for type B meningococci are ineffective at any age, for reasons unknown, and, as noted earlier, most cases of meningococcal meningitis arc caused by type B and type C organisms. The meningococcal vaccines are the purified polysaccharide capsular antigen. We have been working with an H. in~uenzae type b vaccine prepared from purified PRP. After this vaccine was shown to be nontoxic and immunogenic in adults, we began tests in infants and young children. Immunizations are well tolerated, and a single injection triggers a significant antibody response in up to 95% of individuals older than two years. On the basis of this type of study, large-scale efficacy trials arc now under way in this country and abroad (in Finland). Preliminary results have been both promising and discouraging. It appears that the vaccine is highly effective in children older than two years but is not effective in younger children. The problem, of course, is that about 70% of all cases of H. influenzae meningitis occur in children younger than two years. Of the several possible alternative approaches, one is to make the bacterial antigen more complex (combining polysaccharide and protein). Studies have been initiated with such a preparation; the results are encouraging and the work is continuing. An alternative approach (being pursued by Robbins and colleagues) derives from the observation that certain Escherichia coli strains possess antigens cross-reactive with PRP; conceivably, feeding of one of these apparently innocuous strains could induce immunity against H. in~uenzaediscase. Pneumococcal vaccines are being tested for prevention of otitis media; the prevention of pneumococcal meningitis is not being evaluated. For the present, then, physicians in practice should be kept informed of ongoing programs to achieve safe and effective immunity in the age groups most vulnerable to bacterial meningitis. Their immediate focus, however, must be on ensuring early diagnosis and prompt therapy, including necessary supportive care - which are critical to the survival of healthy children affected with acute bacterial meningitis. D
