AGPs' guide to meningococcal disease, titled Meningococcal Meningitis and Septicaemia: Diagnosis and Treatment in General Practice, was first published in 1996 by the Meningitis Research Foundation.
The advice was based on the clinical experience of a multidisciplinary working party and aimed to improve clinical outcome by early recognition and treatment in primary care. This supported other guidance, including that issued by the chief medical officer as early as 1988.1 In spite of this advice, pre-admission use of penicillin by GPs in patients with meningococcal disease remained low.2,3
While meningococcal disease remains the most common infectious cause of death in children in Britain, overall mortality has improved to less than 10% of all cases. This improvement has been attributed to the recognition of septicaemia as a distinct entity requiring a specific approach as well as early aggressive management.
However, the diagnosis of septicaemia remains difficult for both paediatricians and GPs, and towards the end of 1999 it was felt that the guidance required revision with a particular emphasis on the diagnosis of septicaemia, with the inclusion of more detailed information specifically for doctors.
It was also felt that an explanation of the mechanism of the disease process would help to explain and reinforce the importance of the clinical findings in meningococcal disease.
Development of the guidelines
A new draft of the booklet was written by a paediatrician who was conducting a national confidential enquiry into healthcare delivery and outcome in meningococcal disease, in collaboration with two officers of the Meningitis Research Foundation.
No systematic literature review was conducted, but the Meningitis Research Foundation had accumulated an extensive database of published data on the clinical presentation and early management of meningococcal disease, which was made available to the reviewers.
The revised booklet, together with a reference list, was sent to a group comprising five GPs, six paediatricians, two accident and emergency consultants and one registrar, two adult physicians, one with a consultant post in infectious diseases, and two public health consultants. They were asked to suggest improvements and their comments were considered, summarised and incorporated into the guidance where appropriate.
The pilot version of the guidelines, and a questionnaire, were then sent to a random sample of 1100 GPs. Their comments and criticisms have been collated and considered in the preparation of the final version, which is due to be published shortly.
Limitations of the current published data
The literature review identified a substantial amount of published data on the presentation and management of meningococcal disease at the time of hospital admission, but only three studies on clinical features at the time of the primary contact by the GP or in casualty.
This was considered to be a weakness in the available evidence as it is known that the disease evolves rapidly and may have appeared quite different at initial onset and when first assessed in the community or in a casualty department.
As meningococcal disease is a relatively rare occurrence, its prospective study presents considerable methodological difficulties. This is illustrated by the fact that all of the studies on clinical presentation were descriptive, and all except two, with samples sizes of 69 and 126 patients, were conducted retrospectively.
Problems with early diagnosis
During the early prodromal stage of the disease, patients may present with non-specific symptoms similar to those of an acute self-limiting febrile illness. The triad of rash, neck stiffness and headache is not the classic presentation of meningococcal disease, and the symptoms occur together in only 13% of cases and only in those with well-established meningitis.4
Although there is no evidence on the effect of information given by practitioners to patients, it is considered to be good practice to give adequate information to parents of children with febrile illness where no obvious cause is apparent.
This should include advice about the typical meningococcal rash as well as the 'tumbler test' (Figure 1, below) and encouragement to seek immediate medical help if the patient's condition deteriorates.
|Figure 1: The tumbler test|
|If a tumbler is pressed firmly against a petechial or purpuric rash it does not blanch,
but remains visible through the glass. A non-blanching rash in a febrile or unwell patient
constitutes a medical emergency
A wall chart showing physical signs in children with meningococcal disease is shown in Figure 2 (below).
|Figure 2: Wall chart showing physical signs in children with meningococcal disease|
The disease pathway
Figure 3 (below) illustrates the evolution of symptoms of septicaemia and meningitis. The non-blanching rash is the key clinical factor in diagnosing meningococcal disease and the disease should be suspected in any child who presents with such a rash.3,5
|Figure 3: Evolution of symptoms of septicaemia and meningitis|
A non-blanching rash is present in up to 80% of bacteriological proven cases,6 although it cannot be relied on in earlier stages of the disease when it may be present in only about 50% of cases at first presentation. However, non-blanching rashes also occur in other illnesses, e.g. viral infections, Henoch–Schönlein purpura and thrombocytopenic purpura.
The positive predictive value of such rashes for meningococcal disease may be lower in adults, and one North American study7 has found it to be relatively low, particularly in otherwise well children. But as meningococcal disease is the only illness that is immediately life-threatening, it is essential to consider this diagnosis in the first instance and manage both adults and children accordingly, unless there are good clinical grounds to do otherwise.
There is some evidence to suggest that the rash may be blanching and maculopapular in the early stages, or present with scanty purpuric or petechial lesions,3,8 and such a finding should not deter clinicians from making the diagnosis.
The disease pathway published in the guidelines is based on the extensive experience of clinicians in the department of paediatrics at St Mary's Hospital, London. This department has a special interest in meningococcal disease and has studied more than 400 children with the disease since 1992.5 The St Mary's algorithm emphasises the difference between meningitis and septicaemia. While the majority of children present with meningitis alone, up to 10% have features of septicaemia alone and 40% have features of both meningitis and septicaemia.
As signs of early shock are difficult to detect, it was felt that the revised guidelines should emphasise the importance of features of possible shock that are a consequence of the underlying physiological compensatory mechanisms which ensure perfusion of vital organs at the expense of other tissues.
An understanding of the disease process and the evolution of shock help to make sense of the early clinical changes, including tachycardia|and peripheral vasoconstriction resulting in cold and sometimes discoloured peripheries and prolonged capillary refill time.5 Reduced renal perfusion leads to decreased urine output, and tachypnoea is a compensatory mechanism to correct the acidosis caused by reduced tissue perfusion.
Later signs of decompensated shock are decreased level of consciousness and hypotension, but these are pre-terminal signs.5,9
The guidelines provide detailed advice about checking capillary refill time, which should be checked both peripherally and centrally. Normal values for vital signs, including heart rate, respiratory rate and blood pressure, are published in the guidelines, based on the guidance and values from the Advanced Paediatric Life Support Manual.10
Meningococcal disease occasionally presents with other unusual symptoms including joint aching, muscle pain, and abdominal pain. As these are relatively unusual findings in self-limiting febrile illnesses they should lead the clinician to at least consider a diagnosis of meningococcal disease.
The classic presentation of meningitis, with headache, neck stiffness and photophobia, has been widely described in the published literature. Although these features are not specific for meningococcal disease and may occur in other forms of meningitis, meningococcal meningitis is the most likely treatable cause and should be the presumed diagnosis until excluded.
The diagnosis of meningococcal disease in children under 18 months may be more difficult to make on clinical grounds, and additional signs such as a tense fontanelle, central cyanosis, altered cry (especially high pitched or moaning), reduced interactivity or eye contact, and abnormal tone may give clues to the diagnosis.
These features have been shown to be associated with moderate or serious illness in a large study of symptoms and signs in 1007 children younger than 6 months of age.11
In a North American study of children up to 36 months of age, albeit in a setting with a significantly lower incidence of meningococcal disease, individual symptoms such as reduced responses to social overtures with expressionless and vacant responses had a lower positive predictive value for serious illness. However, when taken together with other factors, including quality of the cry, reaction to parent stimulation, state variation (level of consciousness), colour, and hydration, these symptoms were highly predictive of serious illness.12
Treatment and further action
The doses of benzylpenicillin for use in children of different ages are published in the guidelines. Adults and children aged 10 years or older should be given 1200mg. Children aged 1–9 years require 600mg and those under a year 300mg.
Some controversy remains over the benefit of pre-admission penicillin. Early treatment has been widely recommended and has been shown to reduce morbidity from meningococcal disease in a number of studies.13–15 The number of subjects in these studies was small and the reduction in mortality did not reach statistical significance until data from three comparable studies were combined to report on 487 patients with meningococcal disease.
Those treated with parenteral penicillin before transfer to hospital had a mortality of 4.7% compared with 11.5% in those not treated.16 One study found a statistically significantly higher mortality in patients receiving parenteral antibiotics.17 One explanation involving the harmful release of endotoxin and cytokines mediated by antibiotic use was shown to be unfounded.18
A more plausible explanation for the relatively small benefit of early antibiotic therapy is that the patients most likely to be treated were those with more florid symptoms. These were also the patients with more severe or advanced illnesses, who may have carried poorer prognoses.
While there is no published evidence to support the benefit of intravenous over intramuscular penicillin, the systemic absorption of antibiotic injected into poorly perfused muscle tissue is likely to be very slow. The guidelines advise intravenous administration of benzylpenicillin unless a vein cannot be found, in which case it should be given into well-perfused muscle tissue.
Previous anaphylaxis is the only contraindication to the use of penicillin, and its benefits in acute meningococcal disease significantly outweigh the small risk of undiagnosed anaphylaxis.
If facilities are available and the patient has signs of shock or reduced level of consciousness, supportive treatment can be administered, including airways management, oxygen, and intravenous fluids, but these should not delay the early use of antibiotic therapy and immediate transfer to hospital by the quickest means of transport, usually 999 ambulance.
How will the guidelines improve patient care?
The guidelines aim to promote best practice in the management of ill febrile patients in primary care, particularly when meningococcal disease is suspected. The emphasis on septicaemia is intended to raise awareness of this presentation among primary care practitioners.
It is hoped that the diagnosis of meningococcal disease will be made at an earlier stage, when antibiotics, preferably administered intravenously,Òare more likely to have a beneficial impact on the course of the illness. This will contribute to the efforts of accident and emergency and paediatric departments to reduce the mortality to well below 10%.
- Copies of Meningococcal Meningitis and Septicaemia: Diagnosis and Treatment in General Practice, and the wallchart Physical Signs in Children with Meningococcal Disease, are available from the Meningitis Research Foundation, Midland Way, Thornbury, Bristol BS35 2BS (tel 01454 281811; 24-hour helpline freephone 080 8800 3344).
- Department of Health and Social Security. Meningococcal Infection: Meningitis and Septicaemia. London: HMSO, 1988 (CMO88/2).
- Wood AL, O'Brien SJ. A primary care perspective of meningococcal disease. J Pub Health Med 1998; 20: 382-5.
- Granier S, Owen P, Pill R, Jacobsen L. Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information. Br Med J 1998; 316: 276-9.
- Palmer SR, Corson J, Hall R et al. Meningococcal disease in Wales: clinical features, outcome and public health management. J Infect 1992; 25: 321-8.
- Pollard AJ, Britto J, Nadel S et al. Emergency management of meningococcal disease. Arch Dis Child 1999; 80: 290-6.
- Marzouk O, Thomson AP, Sills JA et al. Features and outcome in meningococcal disease presenting with maculopapular rash. Arch Dis Child 1991; 66: 485-7.
- Mandl KD, Stack AM, Fleisher GR. Incidence of bacteremia in infants and children with fever and petechiae. J Pediatr 1997; 131: 398-404.
- Riordan FA, Thomson, APJ, Sills JA, Hart CA. Who spots the spots? Diagnosis of early meningococcal disease in children. Br Med J 1996; 313: 1255-6.
- Flaegstad R, Kaaresen PI, Stokland R, Gutteberg T. Factors associated with fatal outcome in childhood meningococcal disease. Acta Paediatr 1995; 84: 1137-42.
- The Advanced Life Support Group. Advanced Paediatric Life Support. London: BMJ Publishing Group, 1997.
- Morley CJ, Thornton BA, Cole TJ et al. Symptoms and signs in infants younger than 6 months of age correlated with the severity of their illness. Pediatrics 1991; 88: 1119-23.
- McCarthy PL, Sharpe MR, Spiesel SZ. Observation scales to identify serious illness in febrile children. Pediatrics 1982; 70: 802-9.
- Woodward CM, Jessop EG, Wale MCJ. Early management of meningococcal disease. Commun Dis Rep CDR Rev 1995; 5(9): R135-7.
- Strang JR, Pugh EJ. Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. Br Med J 1992; 305: 141-3.
- Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. Br Med J 1992; 305: 143-7.
- Cartwright K, Strang J, Gossain S, Begg N. Early treatment of meningococcal disease (Letter). Br Med J 1992; 305: 774.
- Sorensen HT, Moller-Petersen J, Krarum HN et al. Early treatment of meningococcal disease (Letter). Br Med J 1992; 305: 774.
- Brandtzaeg O, Kierulf P, Gaustad P et al. Plasma endotoxin as a predictor of multiple organ failure and death in meningococcal disease. J Infect Dis 1989; 159: 195-204.