Journal of Infection (I992) 25, 321-328

EPIDEMIOLOGY Meningococcal

disease in Wales: clinical features, outcome and public health management

S. R. P a l m e r , * J. C o r s o n , * R. Hall, I S. P a y n e , ~ J. L u d l o w , 2 B. D e e r e , 3 H. Jones, 4 S. Kaul, s J. S t u b b i n s , s R. W i l l i a m s , s M. W a l a p u , 6 A. S p e n c e , 7 P. Jenkins s a n d D. D o n a l d 9

* Public Health Laboratory Service, Communicable Disease Surveillance Centre, Welsh Unit, Abton House, Wedal Road, Cardiff CF4 3 Q X and 1 Clwyd Health Authority, 2East Dyfed Health Authority, a Gwent Health Authority, 4 Gwynedd Health Authority, 5Mid Glamorgan Health Authority, 6Pembrokeshire Health Authority, 7Powys Health Authority, 8 South Glamorgan Health Authority and 9 West Glamorgan Health Authority, Wales, U.K. Accepted for publication 14 April I992

Summary In Wales, in 1988 , 119 patients with meningococcal disease were identified, so giving a crude annual incidence of 4'2 patients per IOOOOO population. The combined classical clinical features of fever, vomiting, neck stiffness, headache and purpuric rash were identified in only 9 % of patients. Fever and vomiting were the commonest symptoms, both being present in 6o % of patients. A rash was noted in 77 % of patients but neck stiffness in only 39 %. Rash was more common in children, headache and photophobia in adults. A total of 13 patients died, the fatality rate increasing with age from 3 % in infants to 2o % in older teenagers and adults. Only 15 % of 75 patients admitted to hospital by general practitioners were known to have received intravenous or intramuscular penicillin before admission as recommended by the Chief Medical Officers of the Health Departments in the U.K. Only 24 % of patients received rifampicin to clear nasopharyngeal carriage before or at discharge from hospital. Altogether, 375 household contacts of patients were identified. At least 84 % of them received chemoprophylaxis.

Introduction Infection with Neisseria meningitidis classically causes acute meningitis with or w i t h o u t septicaemia. Early recognition and t r e a t m e n t are essential for a successful outcome. 1 A combination of fever, vomiting, neck stiffness and p u r p u r i c rash are usually considered to be characteristic features b u t in I987, d u r i n g the most recent meningococcal disease epidemic in Wales, local clinicians reported that atypical presentations were becoming more common. It has been suggested that the pattern o f disease m a y vary with the strain of m e n i n g o c o c c u s ) We therefore sought to clarify the range o f clinical presentations. W e also took the o p p o r t u n i t y to review the use of penicillin before the admission of patients to hospital as well as the public health aspects. oi63-4453/92/o6o32I +08 $08.00/0

© I992 The British Society for the Study of Infection

322

S. R. P A L M E R E T A L .

Methods

All Medical Officers for Environmental Health in Wales agreed to complete a questionnaire for each case of meningococcal disease reported in their areas during I988, and to include data from general practitioners, hospital clinicians and microbiologists. Patients were identified from statutory notifications, reports of laboratory isolations of N. meningitidisfrom blood and C S F as well as from data provided by Manchester Public Health Laboratory (PHL) Meningococcal Reference Laboratory. Patients with clinical features of meningitis but whose diagnosis was not confirmed by blood or C S F culture, were considered to have meningococcal disease when a purpuric rash and an abnormal C S F were reported also. Results

A total of z 19 patients (63 males) were identified. T h e y included zo without an organism cultured from blood or C S F and without evidence of a purpuric rash. In five of these IO, diplococci were seen in the C S F ; in the other five, the C S F was abnormal. T h e crude annual incidence, in z988, in Wales was 4.2 p a t i e n t s / I o o o o o population. T h e age-specific incidence was 83/IOOOOO in infants, 35/100000 in z-4-year-old children, 5 / I o o o o o in 5-I4-year-old children and I / z o o ooo in adults. T h e peak incidence was between January and April, with a smaller peak towards the end of the year. T h e fatality rate was 3 % ( z / 3 I ) in infants, i o % (5/5I) in 1- 4 year olds, I 8 % (3/I7) in 5 - I 4 year olds and 2o % (4/20) in older teenagers and adults. Microbiology

A m o n g the zo5 of the I I i meningococcal strains identified at Manchester Public Health Laboratory, there were 77 group B strains (74 % sulphonamide sensitive), 27 group C strains (63 % sulphonamide sensitive), and I group Y strain (sulphonamide sensitive). T h e r e were 26 different serotypes, the most c o m m o n being Bzbnt (23 patients), B I 5 P I . I 6 (I2 patients), Bnt nt ( I I patients), Bnt P I . I 5 (seven patients) and Cnt nt (nine patients). Analysis of postal codes of patients showed only two postal areas in which there was more than one case of the same type (two patients with Bzbnt in postal area S A I o and three patients with Cnt nt in postal area CF3). Twelve patients with culture-confirmed infection died; in one, the organism was untyped, three had type Bzbnt, and three had type Cnt nt. Of the others, one had type B 15 P I. 16, one had type BI5 nt, one had type Bnt nt, one had type C2a PI.2 and one had type Y I 4 nt. Clinical features

Clinical details were reported for 96 patients (Table I). Of these, I7 (I 8 %) had a positive blood culture but did not have neck stiffness, photophobia, or positive C S F culture; neither were diplococci seen in the CSF. T h e y were considered to have had septicaemia without meningitis. T h e s e patients comprised 3/25 ( i 2 % ) infants, 5/39 (x3 %) I - 4 year olds, 5/I4 (36%) 5-x4 year olds and 4/18 (22 %) older teenagers and adults. T h e case fatality rate was

Meningococcal disease in Wales

323

T a b l e I Symptoms and signs reported in cases of meningococcal disease in

Wales Age in years

Number with clinical data Fever Vomiting Fever and vomiting Refusal of feeds Loss of appetite Listless Floppy Pallor Photophobia Headache Neck stiffness Rash -Purpuric rash -Other rash only Fever, vomiting and rash Neck stiffness and rash Neck stiffness or rash Neck stiffness, rash and headache Neck stiffness, vomiting and headache Convulsions Coma Shock

< I

I- 4

5-I4

15-

Total

25 (IOO%)

39 (IOO%)

I3 (IOO%)

I8 (IOO%)

96(IOO%)

20(80%) 14(56%) 13 (5 2 %) 16(64 %) -13(52%) 5(20%) 8(32%) 3(12%) -5 (20 %) I9(76%) I3 (52 %) 6(24%) 9 (36 %)

35(90%) 31(79%) 28 (72 % ) 15 (38 %) 18(46%) 27(69%) I2(3I %) I2(3I %) 3(8%) IO(26 %) I9(49 %) 35(90%) 32(82%) 3(8%) 24(62%)

II(85%) II(85%) 8 (62 % ) -5(38%) 5(38%) 1(8%) 6(46%) 2(I5%) 9 (69 %) 5 (38 %) II(85%) 9(69%) 2(I5% ) 5 (38 %)

13(72%) I2(67 %) 9 (50 %) -7(39%) 5(28%) -2(II%) 5(28%) 13 (72 o/o) 8 (44 %) 9(50%) 8(44%) 1(6%) 5 (28 %)

82(85%) 68(7I %) 58 (60 %) -30(31%) 50(52%) 18(19% ) 28(29% ) I3(I4%) 32 (33 %) 37(39%) 74(77%) 63(66%) II(II %) 43 (45 %)

3 (I2 %)

17 (44 %)

5 (38 %)

3 (17 %)

25 (26 %)

2i (84 %)

37(95%)

I2 (92 %)

14(78%)

84(88%)

1(4°/o)

5(13%)

4(3I %)

3(17%)

13(14%)

4(16%)

I2(3I %)

5(38%)

5(28%)

26(27%)

3(I2%) 1(4%) 3(I2%)

6(I5% ) 3(8%) 8(2I %)

I(8%) I(8%) --

I(6%) 5(28%) 4(22%)

II(II%) 10(10%) I5(I6%)

4 / I I (36 %) in n o n - m e n i n g i t i s patients compared with 9/85 (IX %) in others (Odds Ratio 4"8, 95 % C.I. o'95-24"I5, Fisher's exact P = o'o4). T h e triad o f fever, neck stiffness and a rash was reported in only I3 % patients, while either neck stiffness or a rash was present in 87 % patients. M o s t infants were reported to have fever b u t only 2o ~/o had neck stiffness. Neck stiffness together with a rash was observed in only two infants. H a l f of the children aged I - 4 years of age h a d neck stiffness and 9o % h a d a rash. In the 5 - r 4 year olds, neck stiffness was less c o m m o n t h a n in y o u n g e r children (P < o'o5). In older teenagers and adults, headache was a c o m m o n feature b u t only h a l f o f t h e m h a d a rash. Neck stiffness or p u r p u r i c rash in patients with type B2bnt meningococci, the c o m m o n e s t strain, were just as c o m m o n as in patients with other strains. Patients infected with type B I 5 Pr. I6 strains were

324

S.R. P A L M E R E T A L .

significantly less likely to have had neck stiffness than patients infected with other strains (0/8 v s . 38/88, Fishers exact P = 0.02). Deaths

One infant died. He had had coryza for 3-4 days and a non-purpuric rash on one arm for 3 days. At 13.o0 hours on the day of his death, he was noted to be feverish and listless, and he vomited. At 23.00 hours he was comatose and had generalised convulsions. A purpuric rash was noted. Five children aged 1-4 years died. A I-year-old child became ill in the evening, refused to feed, and was listless. By the following mid-morning a purpuric rash had developed. T h r e e hours later the child was taken to hospital in shock and died at 17.3o hours. A 2-year-old child was ill for 3 days with vomiting and diarrhoea. At 23.00 hours the child suddenly became feverish, listless and floppy with pallor. One and a half hours later the child was taken to hospital in shock, comatose and with a purpuric rash. A 2-year-old child was feverish at 22.00 hours. T h e following day the GP visited and made the diagnosis of odds media. By 2 I.OO hours on the third day, the child was grey, floppy and listless with neck stiffness and a purpuric rash. An hour later, the child was taken to hospital in coma and died 20 days later. A 4-year-old child was ill with vomiting for I day and then developed headache and a purpuric rash. T h e following day, the child was admitted to hospital in shock. A 3-year-old child was ill at 23.00 hours with vomiting. By 09.00 hours the next day he was listless. At 13.oo hours a purpuric rash was noted. He died 12 h later in hospital. T h r e e children aged 5-14 years died. A 7-year-old child went to bed with a sore throat and during the night vomited. T h e next day he developed fever and by 16.oo hours a purpuric rash was observed. T h e GP was called but the patient died while admission to hospital was being arranged. Post-mortem, the meninges were normal but the adrenal glands were haemorrhagic. A 6-year-old child was ill with vomiting and a purpuric rash. T h e following day the child was taken to hospital. An 8-year-old child was ill with fever, vomiting, loss of appetite and headache, but no rash. T h e patient died in the ambulance on the way to hospital. Four teenagers and adults died. A i6-year-old developed fever, headache and sore throat at 07.00 hours, followed 12 h later by photophobia, a purpuric rash and diarrhoea. T h e patient was admitted to hospital 12 h later and died that day. A diabetic teenager was ill at 09.00 hours with fever, headache and a sore throat. At midday she arrived at a casualty department and was admitted to hospital because of poor diabetic control. She did not have neck stiffness or other evidence of meningitis. T h e following day at 09.00 hours, a diffuse macular and blotchy rash was noted. This developed 24 h later into a purpuric rash with shock and grand real seizures. A 22-year-old patient who had had a sore throat for 2 weeks became ill at

Meningococcal disease in Wales

325

18.00 hours with severe headache. At 02.oo hours, the patient vomited and by Io.oo hours the following morning neck stiffness was noted. On admission to hospital at I5.oo hours, the patient was comatose and shocked with fever and a purpuric rash; the patient died 3 h later. A 54-year-old patient was ill at 20.00 hours with fever, a purpuric rash and haematemesis. Six hours later the patient was admitted to hospital and died r2 h after the onset of illness.

Management Eleven (x5 %) of 75 patients known to have been admitted to hospital by a general practitioner were reported to have received penicillin before admission. Eight patients admitted by GPs were noted to have both neck stiffness and purpuric rash before admission but only two were given penicillin. One GP was reported to have said that he did not know that intravenous penicillin was advised in this situation. Of the I3 patients who died, seven were known to have been admitted to hospital by their general practitioners. Penicillin was given before admission to one of these patients. Altogether, 28 patients were known to have received rifampicin on or before discharge from hospital in order to try to eliminate nasopharyngeal carriage of the organism. Rifampicin was not given to 30 patients while for 48 patients information was not forthcoming. A total of 396 household contacts were identified with a mean n u m b e r of household contacts per case of three (range 0-66). Of these, 347 (88 %) were known to have received chemoprophylaxis. In seven health districts, all household contacts were given rifampicin; for one, the data were incomplete. Another 375 close contacts were identified, a mean of four per case (range 0-I9). O f these, 3r5 (84 %) received rifampicin.

Discussion Early recognition of meningococcal disease may be difficult. Definitive diagnosis requires hospital investigations while presumptive diagnosis by general practitioners must be solely on clinical findings. A high degree of awareness must therefore be maintained by all general practitioners. Retrospective assessment of clinical features of patients, as in our study, presents problems. For example, patients were seen by clinicians and the diagnoses made at differing stages of the illness, yet identification of a rash depends in part on the stage of the illness at which an examination is made. Also, the rash in the early stages of illness may be maculopapular before it becomes haemorrhagic3 and may be entirely missed without a thorough examination. Furthermore, it is not possible in practice to standardise the collection of data so that all patients have all possible symptoms and signs assessed according to a standard protocol at set points in time during the course of the illness. T h e frequency of symptoms reported for our patients differs from that of

326

S. R. P A L M E R

ET AL.

some other studies. F o r example, in our patients, fever and vomiting were more often reported (60 %) than in a study in Norway in I 9 8 I - I 9 8 2 ( < 5o %),4 while headache (33 % vs. 66 %) and neck stiffness (39% vs. 66 %) were less common. We found also that infections with strain of type BI5 P I . I 6 , the Gloucester outbreak strain, 5 were significantly less likely to be accompanied by neck stiffness. This may be a chance finding since in Norway where there was a higher incidence of neck stiffness, infections were mostly due to type BI5 PI.I6. 6 Ideally, we should like to know the sensitivity and specificity of groups of clinical symptoms and signs in predicting meningococcal disease. T h e classical features of fever, vomiting, neck stiffness and purpuric rash are likely to be highly specific but insensitive since only 18 % of patients had all these features. One study of children in hospital with fever and petechiae showed that only 7 % had meningococcal disease. 7 In the Gloucestershire Health Authority leaflet, aimed at educating the public in the early recognition of meningococcal disease, five s y m p t o m complexes are described. 'Severe headache, neck stiffness and fever' were reported in only 4 % of our patients, 'vomiting or refusal to feed' in 68 %, 'unconsciousness' (as measured by coma) in Io %, 'discomfort from bright light' in only I 4 % , and a rash in 7 7 % . T h u s , although the presence of symptoms such as fever, a purpuric or petechial rash, neck stiffness and photophobia indicate the need for urgent admission to hospital, their presence cannot be relied u p o n to identify most patients. On the other hand, the absence of several such symptoms may be reassuring. For example, only I I of 96 patients had neither neck stiffness nor rash nor photophobia. Of those I I, only four did not have vomiting and fever, while only three had neither a rash nor vomiting nor neck stiffness. Either neck stiffness or a rash were reported for 87 % of patients. A petechial or purpuric rash, although perhaps the most important clinical sign, may be a relatively late manifestation of infection. It is important, if possible, to recognise the disease before the rash appears. One feature relevant to this is that the clinical symptoms and signs vary with the age of the patient. T h u s , headache was noted as a p r e d o m i n a n t s y m p t o m only in older children and adults. M o s t children, but only half the adults, had a rash. T h e fatality rate in Wales in I988 of I 1% overall is a little higher than might be expected. 8 Also, the age-specific fatality rates increased with age, a finding which differs from that expected on the basis of the ratio of notified cases to deaths in England and Wales in I975-I983. Abbott et al. 8 demonstrated that case fatality ratios were 22 % in infants, falling to 5 % in 5-9 year olds and then rising to 34 % in adults >~ 25 years of age. T h e low fatality rate in infants in Wales of 3 % is consistent with experience in Norway. 9 T h e relatively high case fatality in Wales in 5 - I 4 year olds was surprising and perhaps due to chance, although in the Stroud outbreak, where the overall case fatality was only 3 %, the only two deaths were in teenagers. 5 Slack n reviewed deaths from meningococcal infection in England and Wales in I978. In I7 % of 86 patients there was no evidence of delay in diagnosis or treatment. T h e infection was rapid and overwhelming. In Wales in I988, five of I3 deaths were of patients ill for less than 24 h. We did not consider that possible delays in diagnosis or treatment could be assessed from

M e n i n g o c o c c a l disease in W a l e s

327

data collected in our survey. It was clear, however, that few patients received penicillin from general practitioners as advised b y the Chief Medical Officer in a letter to all doctors in I987 .11 O f the 75 patients k n o w n to have been admitted b y the G P , only I5 % received intravenous or intramuscular penicillin before admission. D e s p i t e the rarity of the disease, all general practitioners should carry in-date intramuscular and intravenous penicillin with them. O f the patients w h o died, only one received penicillin before admission to hospital. W e are unable to judge w h e t h e r deaths w o u l d have been averted if penicillin had been given to the other patients. In one case, deterioration was so rapid that the patient died while the doctor was arranging for admission to hospital. In such fulminant cases, successful intervention w o u l d not seem to be possible. Slack in England and Wales and T o n j u m et a l 3 in N o r w a y f o u n d that the most i m p o r t a n t aspect o f delay in diagnosis was failure of parents to recognise the seriousness of their child's illness. O f the I3 patients w h o died, two had p u r p u r i c rashes the day before admission, one had a rash I2 or more hours before, and one 3 h before admission, suggesting that there was delay in recognising the severity of the illness. T h e administration of chemoprophylaxis to h o u s e h o l d contacts was accomplished successfully t h r o u g h o u t Wales. T h e rationale for rifampicin chemoprophylaxis is to eliminate carriage of the organism in contacts w h o m a y transmit infection to susceptibles32 Consistent with this is the recomm e n d a t i o n to treat patients before discharge from hospital with rifampicin, ~2 since penicillin, while effective as treatment, does not reliably eradicate carriage o f the organism. Patients discharged from hospital have transmitted disease on return home. In I988, in Wales, however, few patients were given rifampicin before or at the time of discharge from hospital. Hospital clinicians need to be r e m i n d e d of the need to give rifampicin to recovered patients before their discharge from hospital. (We thank all general practitioners, hospital clinicians and microbiologists who provided data for this study.) References

i. Welsby PD, Golledge CL. Meningococcal meningitis. Br Med J I99O; 3oo: I I5o-I I5I. 2. Spanjaard L, Bol P, de Marie S, Zanen HC. Association of meningococcal serotypes with the course of disease: serotypes 2a and 2b in the Netherlands, I959-8I. J Infect Dis I987; 155: 277-282. 3. Baxter P, Priestley B. Meningococcal rash. Lancet I988; i: I i66-i I67. 4. Tonjum T, Nilsson F, Bruun JN, Haneberg B. The early phase of meningococcal disease. N I P H Ann I983; 6: I75-I8I. 5. Cartwright KAV, Stuart JM, Noah ND. An outbreak of meningococcal disease in Gloucestershire. Lancet I986; ii: 558-56I. 6. Poolman JT, Lind I, Jonsdottir K, Froholm LO, Jones DM, Zanen HC. Meningococcal serotypes and serogroup B disease in north-west Europe. Lancet I986; ii: 555-557. 7. Baker RC, Seguin JH, Leslie N, Gilchurst MJR, Myers MG. Fever and petechiae in children. Paediatrics I989; 84 : Io5 I-IO55. 8. Abbott JD, Jones DM, Painter MJ, Young SEJ. The Epidemiology of meningococcal infections in England and Wales, I912-I983. J Infect I985; II: 241-257. 9. Halstensen A~ Pedersen SHJ, Haneberg B~ Bjorvatn B~ Solberg CO. Case fatality of meningococcal disease in Western Norway. Scand J Infect Dis I987; I9:35-42.

328

S. R. PALMER E T AL.

to. Slack J. Deaths from meningococcal infection in England and Wales in x978. J R Coll Physicians I982; , 6 : 4 0 - 4 4 . I I. Chief Medical Officer. Meningococcal Infection Meningitis and Septicaemia. Department of Health and Social Security. 2 February I988. I2. PHLS. Meningococcal Infections Working Party. The Epidemiology and control of meningococcal disease. Communicable Disease Report, I989/o8, 24 February I989.

Meningococcal disease in Wales: clinical features, outcome and public health management.

In Wales, in 1988, 119 patients with meningococcal disease were identified, so giving a crude annual incidence of 4.2 patients per 100,000 population...
515KB Sizes 0 Downloads 0 Views