197

Public Health

HÆMOPHILUS MENINGITIS IN PORTSMOUTH STEPHEN

SYLVIA MCLAUCHLAN

J. WARE

Department of Pœdiatrics, St. Mary’s Hospital, Portsmouth

The clinical features and follow-up data of all twenty-five children admitted to a Portsmouth hospital from Jan. 1, 1972,to July 1, 1975, with hæmophilus meningitis were reviewed. Two children died of meningitis and one of other causes. Four have residual damage—two severe, one definite, and one possible. Outcome tended to be worse in cases with the following features: age less than 9 months at the time of illness, difficult diagnosis, antibiotic treatment before admission, combined treatment with chloramphenicol and ampicillin, and difficulties at home. The continuing high morbidity indicates that children with this disease need careful follow-up.

Summary

INTRODUCTION

DESPITE the use of antibiotics, Hœmophilus influenzœ meningitis continues to cause death and handicap in children. Although mortality is falling,’ American and Scandinavian series indicate a continuing high morbidity, with severe or definite sequelx often occurring in over a quarter of survivors (table I). No up-to-date follow-up studies are available in the U.K. We describe our experience of haemophilus meningitis over a 3½year period.

cal, and developmental assessment-where possible with a sibling to act as a control. Where no sibling was available, a child of the same age and street of residence was seen. The examiners did not know whether a child was a case or a control. A health visitor’s report on early development and home conditions for each child, and a headmaster’s report on behaviour and performance for those of school age were obtained. Clinical, neurological, and developmental examination on the Mary Sheridan scale, together with the Stycar hearing test, were carried out by us. All meningitis cases of school age were subsequently examined by an educational psychologist, and all children with suspected developmental problems were seen by a senior educational psychologist (Miss P. M. Wallace). The Wechsler Intelligence Scale for Children or the McCarthy scale were used. Children with suspect hearing were referred to their local audiology service for formal testing. Questionnaires were sent to those children who had moved from the area, and reports were requested from their local medical attendants. RESULTS

Presentation

pronounced seasonal variation, with peak spring and late autumn. Eighteen of the cases were boys (72%). Children were aged twenty-five 6 weeks to 6 years 5 months, eleven (44%) being less than 1 year old. Fifteen cases (60%) had been correctly diagnosed by the general practitioner, all undiagnosed cases were 2y years or less. Thirteen (52%) had received antibiotics before admission. Length of history ranged from a few hours to 5 days (21 days in one case); eleven (44%) had been ill for 24 h or less. Younger children were no more likely than older ones to have a short hisThere was incidence in

tory.

Lethargy and vomiting, the usual presenting symptoms, were found in twenty-one (84%) children. Diarrhoea was a minor feature in 1 child. Convulsions before admission occurred in five (20%), including one known epileptic child. A 7-week-old child presented with high-pitched screaming.

SUBJECTS

AND METHODS

Case-reports of all twenty-five children admitted to St. Mary’s Hospital, Portsmouth from Jan. 1, 1972, to July 1, 1975, with meningitis caused by Hœmophilus influenzce (proven by cerebrospinal fluid [c.s.F.] culture) were examined. All survivors were contacted, and those still living in the area were requested to attend a special clinic for clinical, neurologi-

On admission, all cases appeared ill, almost always with altered consciousness: two were deeply comatose, and in three shock requiring volume expansion was diagnosed. All were febrile (temperature 37.4—411°C), and 1 child became hypothermic (34-9°C) on the 2nd day, before he died. Signs of meningitis were not present in five (20%) and not very pronounced in a further three

TABLE I-MORTALITY AND MORBIDITY OF H&MOPHILUS

MENINGITIS

*Chlor. 193 mg/kg (22); Amp. 328 mg/kg (32); both (Chlor. 168 mg/kg, Amp. 276/kg) (11); one, then the other (17). tSudden infant death syndrome.

Chlor.=chloramphenicol. Sulp.=sulphonamide. Amp.=ampicillin.

198

(15%):

all these children were aged 12months or less, except aged 2tyears who was deeply comatose and died on the 2nd day. Eight children started to have convulsions after admission, bringing the total with seizures to thirteen (52%). In six (five under the age of 12 months) seizures started 6-12 h after admission; one started immediately, and one after 7days, despite good initial improvement. Improvement in general state usually took 4-5 days, though accurate assessment is not possible retrospectively. Fever generally continued for longer, with only five children having a temperature below 37-3°C after 5 days; secondary temperature spikes following several days without fever were common. one

Laboratory Tests Cerebrospinal fl1:lÍd white-cell

counts ranged from 98 was less than 40 Glucose concentration 000/1. mg/dl (2.4 mmol/1) in eleven out of fourteen (78%). Neither of these findings was significantly influenced by length of history or pre-admission antibiotics, although one child with a white-cell count of 98/1 had received tetracycline for 3 weeks: this was the only case in which the diagnosis on admission was in doubt. Protein concentration ranged from 5 to 60 g/1, those who had received antibiotics having significantly lower concentrations than those who had not. Serum-sodium was low (less than 137 mmol/1) in eleven out of sixteen (70%), however, it was less than 132 mmol/1 in only three. Hypoglyca’mia (glucose less than 2.5mmol/1) was present in two of nine cases. Blood-culture was positive in twenty of twenty-one (95%); the child with negative culture had received oral

to

10

penicillin for and c.s.F. cillin.

2

were

days. All organisms grown from blood sensitive to chloramphenicol and ampi-

Treatment

received chloramphenicol (45-170 mg/kg/day), usually as part of initial triple therapy (with penicillin and sulphadimidine). On the basis of a gram-stain one child was treated for meningococcal meningitis with penicillin and sulphadimidine alone for 12 h until haemophilus was grown. The other two drugs were withdrawn in most cases when the organism was identified, and in ten children ampicillin (110-220 mg/kg/day) was added. Treatment was continued for 9-14 days, usually intravenously for 4-5 days, then orally. One child had a second course for 3ydays because of persistent fever and a low c.s.F. glucose (20 ’mg/dl) at 2 weeks, but none had bacteriological relapse. No neutropenia was detected in any child, nor was the lowest recorded post-treatment blood white-cell count influenced by the dose of chloramphenicol. Nearly all children received anticonvulsants, whether or not seizures had occurred. Five received steroids, and two received intrathecal streptomycin. All

children

Outcome

Deaths.-Two children died within 48 h of admission (table n). One baby aged 6tmonths made a complete recovery, but was found dead in his cot 16 days after admission. Necropsy revealed asphyxia due to inhalation, with no abnormality in the central nervous system. Follaw-up.-Of the twenty-two survivors, seventeen (then aged 1 yr 9 mo-9 yr 7 mo) attended our assess-

TABLE II-DETAILS OF THREE DEAD AND FOUR DAMAGED CHILDREN

199

clinic. Six were of school age. All five survivors who had moved away replied to our questionnaire, and reports were obtained from their local pxdiatrician or community physician, usually after a special examination. Eighteen children (72%) have recovered completely and are developing normally. Two are severely handicapped, and will require institutional care. One has mild but definite brain damage, and one has problems which cannot with certainty be attributed to the meningitis (table II). No child had clinically significant hearing loss, apart from one with unilateral glue ear who has been treated by myringotomy with good results. No neurological problems were encountered among the control ment

children. Possible Factors affecting Outcome in Survivors

Although numbers were too small for any firm conclusions to be drawn the following features were noted: (1) Three of seven children aged’less than 9 months at the time of infection were damaged (two severe cases, one possible), while only one of fifteen over 9 months had definite damage. (2) Three of thirteen children with seizures before or after admission weredamaged (two severe cases and 1 possible), while only one of twelve without seizures had definite damage. Overall, younger children had no increased risk of convulsions, though they tended to have their first seizures shortly after admission, whereas older children had seizures before admission. Outcome was not related to the timing of seizures. (3) All three children with severe or definite damage were undiagnosed and had received antibiotics before admission. (4) Three of ten children treated with chloramphenicol and

ampicillin were damaged (two severely,

one

pos-

sibly) while one of fifteen who received chloramphenicol alone had definite damage. (5) All four damaged children had some kind of home problem (parents separated, unemployment, poor hygiene, poor clinic attendance, Cc) while only six of eighteen undamaged children had such problems. Outcome c.s.F.

was not

related

findings, haemoglobin

to sex,

length

concentrations

sion, dose of chloramphenicol,

or

degree

or

of

history,

on admisduration of

fever. DISCUSSION

Hxmophilus meningitis affects mainly pre-school children, most commonly in the first year of life; incidence decreases with age. It is more common in boys. Although onset may be more gradual than in other forms of meningitis, especially meningococcal, nearly half our children at all ages had been ill for less than 24 h before admission. Diagnosis may be difficult in infancy as signs of meningitis may be very slight or not present, and the disease should be suspected in any vomiting infant who is generally unwell. Suspicion is heightened if the child has received antibiotics. In a gram-stain hxmophilus may closely resemble meningococcus, and any child with suspected bacterial meningitis should be treated for all common pathogens until the results of culture are known, whatever microscopy of the c.s.F. may suggest.

Of the thirteen children with seizures, six had their first convulsion 6-12 h after starting treatment. All but one were less than 1 year old. Whether this timing of seizures was caused by endotoxins released from dying organisms, rapid fluid shift after intravenous therapy, fever, or as part of the natural history of the disease, is not clear. Mean temperature was higher in these children than in those who did not have seizures, though not significantly so, and the age incidence was well below the age when febrile convulsions are most common. Seizures were unrelated to the quantity or type of intravenous fluid given, and though mean serum-sodium was lower in those with convulsions, the difference was not significant. In view of the possible association between seizures and long-term damage in these children, and those investigated by others,8 all children with meningitis should be given anticonvulsants in full dosage on

admission.

Chloramphenicol was the mainstay of our treatment since resistant organisms are very rare.9 In our view it is the drug of choice despite the small risk of granulocytopenia. The addition of ampicillin does not seem to be beneficial, and indeed has been associated with increased long-term morbidity, particularly deafness.7,1O On rare occasions when chloramphenicol produces granulocytopenia, ampicillin in high doses may be given instead, or a combination of sulphonamide and streptomycin if the organism is ampicillin-resistant. II Follow-up.-Because of the small numbers and wide age-range of the children tested, it was not possible to compare their performance directly with that of controls. Our aim was -to identify children in whom the illness had had long-term effects, particularly minor handicaps which might be missed in the pre-school and school setting. Four of the nine adverse prognostic factors identified by Herson and Todd8 were present in our series-i.e., severe coma (one died, one severely damaged), hypothermia (one case, died), seizures, and low age. Several others are suggested: difficult diagnosis, pre-admission antibiotics, addition of ampicillin to chloramphenicol in treatment, and adverse home factors.

Our results, like those of previous workers, indicate that extended follow-up is essential for these children, especially those affected in infancy, since long-term morbidity is still considerable. We thank Mrs J. Taylor and Mrs E. Anderson for organising our special clinics; Mr Robert Stratford and his colleagues at the Department of Psychology, Southampton University, for help with the assessments ; and Dr G. M. Lewis, Dr M. J. Hardman, Dr R. J. Hallett and Dr W. B. O’Driscoll for permission to study their patients.

Requests for reprints should be addressed to S. J. W., Paediatnc Department, Southampton General Hospital, Southampton S09 4XY. REFERENCES

1. 2. 3.

Peter, G., Smith, D. H. Pediatrics, 1975, 55, 523. Dodge, P. R., Schwartz, M. N. New Engl. J. Med. 1965, 272, 1003. Sell, S. H. W., Merrill, R. E., Doyne, E. O., Zimsky, E. P. Pediatrics, 1972,

49, 206. Sproles, E. T., Azerrad, J., Williamson, C., Merrill, R. E. J. Pediat. 1969, 75, 782. 5. Schulkind, M. L., Altemeier, W. A., Ayoub, E. M. Pediatrics, 1971, 48, 411. 6. Feigin, R. D., Stechenberg, B. W., Chang, M. J., Dunkle, L. M., Wong, M. L., Palkes, H., Dodge, P. R., Davis, H.J. Pediat. 1976, 88, 542. 7. Lindberg, J., Rosenhall, U., Nylen, O., Ringner, A. Pediatrics, 1977, 60, 1. 8. Herson, V. C., Todd, J. K. ibid. 1977, 59, 35. 9. Kinmonth, A., Storrs, C. N., Mitchell, R. G. Br. med. J. 1978, i, 694. 10. Gamstorp, I., Klockhoff, I. Devl. Med. Child. Neurol. 1974, 16, 678. 11. Barkin, R. M., Greer, C. C., Schumacher, C. J., McIntosh, K. Am.J Dis. Child. 1976, 130, 1318. 4.

Haemophilus meningitis in Portsmouth.

197 Public Health HÆMOPHILUS MENINGITIS IN PORTSMOUTH STEPHEN SYLVIA MCLAUCHLAN J. WARE Department of Pœdiatrics, St. Mary’s Hospital...
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