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New guidelines for management and prevention of meningococcal disease in Australia

Mahomed S Patel, Peter J Collignon, Charles R Watson, Robert J Condon, Richard R Doherty, Angela Merianos and Gregory J Stewart (on behalf of the Meningococcal Disease Working Party of the National Health and Medical Research Council)

The incidence of invasive meningococcal disease in Australia has increased over the past decade, and in April 1997 the National Health and Medical Research Council published guidelines for management of patients with meningococcal disease and their contacts. These guidelines emphasise the need for immediate intravenous antibiotic treatment of patients with suspected meningococcal disease, before transfer to hospital or lumbar puncture. When possible, blood for culture should be collected before antibiotic therapy, if this does not delay treatment. (MJA 1997: 166: 598-601)

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Introduction - Epidemiology - Vaccines - Patient management - Management of contacts - Identification and management of an outbreak - Acknowledgements - References - Authors' details

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Introduction

 The epidemiology of meningococcal disease in the industrialised world is changing, with increases in the incidence of both sporadic disease and outbreaks. These increases have been associated with the spread of virulent clones of meningococci belonging to serogroups B and C,1-6 leading to the suggestion that meningococcal disease should be regarded as an "emerging" infectious disease.4,5 Meningococcal disease affects mainly children under five years of age and adolescents, and can cause death in previously healthy children within several hours of onset.

Guidelines for the management of patients with meningococcal disease and their contacts have been developed by the Meningococcal Disease Working Party of the National Health and Medical Research Council (NHMRC). Draft guidelines were distributed for comment in 1995, and the final version was published in April 1997.7

In this article, we summarise the guidelines document with the aim of providing succinct guidance for management of patients and their contacts and for identifying and managing outbreaks (see Box 1).  

Epidemiology

 In Australia, incidence of disease caused by meningo- coccus (Neisseria meningitidis) has increased over the past decade.6,8-10 With the decline of invasive disease caused by Haemophilus influenzae type b (Hib) since the introduction of the conjugate Hib vaccine in 1993, meningococcus has become the major cause of childhood meningitis in Australia. The incidence of meningococcal disease varies seasonally, rising in June and peaking in October each year.10 Most cases in the past decade were sporadic, but clusters and outbreaks were also reported.11-16

There are 13 serogroups of N. meningitidis, but serogroups A, B and C account for over 90% of invasive isolates, with serogroup B causing most disease. However, the incidence of disease caused by serogroup C has increased over the past decade. In 1995, 66% of isolates submitted to Australian reference laboratories were serogroup B and 28% were serogroup C.17 Serogroup A is often associated with epidemic disease and was responsible for a prolonged outbreak in Aboriginal communities in central Australia.11  

Vaccines

 No one vaccine is effective against all strains of N. meningitidis. The quadrivalent polysaccharide vaccine against serogroups A, C, Y and W135 is effective in older children and adults, but less so in younger children, particularly those aged under two years.18 A conjugate vaccine against serogroups A and C was highly immunogenic in young infants in Gambia19 and is the subject of further immunogenicity studies in the United Kingdom and the United States. There are plans to start phase III, or clinical, trials, and the United Kingdom has signalled its intention to incorporate this vaccine into the routine childhood vaccination program.20 In contrast, an effective vaccine against serogroup B is not yet widely available, but trials of candidate vaccines against the outer membrane protein of some strains have shown efficacy of 50%-80%.21

In Australia, meningococcal vaccination with the combined A-C-Y-W135 vaccine is recommended for individuals with functional or anatomical asplenia, who are at increased risk of meningococcal, pneumococcal and other infections. They should receive meningococcal and pneumococcal vaccines every five years. About 600 splenectomies are performed each year in Australia; if this procedure is planned electively, the vaccines should be given two weeks before surgery.

School- or community-based vaccination programs have also been used in Australia to manage clusters and outbreaks of meningococcal disease.6,11-16 Criteria for vaccination programs are described below.  

Patient management

 Effective management of an individual with meningococcal disease requires early intervention with effective antibiotics plus careful attention to associated manifestations, such as shock and coagulopathy. It therefore relies on early diagnosis.  

Clinical diagnosis

 The appearance of a petechial rash in association with fever, vomiting and drowsiness is highly suggestive of meningococcal meningitis and an indication for early empirical therapy. However, many patients may have a non-distinctive rash or no rash at all, and not all patients with invasive meningococcal disease have meningitis, many having only bacteraemia. Early recognition of meningococcal disease depends most of all on the clinical suspicion of the physician, and diagnosis can be difficult with sporadic cases unless there is high awareness of the problem in the community and among health care providers.  

Empirical therapy (before hospital admission)

 When meningococcal infection is suspected clinically, immediate empirical antibiotic therapy is indicated, before formal diagnosis, transfer to hospital or identification of an organism.22-23 This is particularly important in patients with signs of haemorrhagic disease or actual or incipient shock. However, to confirm the clinical diagnosis, blood for culture should be collected before the antibiotic is given, when this is possible without delaying treatment. The blood specimen should accompany the patient to hospital.

At present, nearly all meningococcal isolates are sensitive to penicillin, but as other invasive pathogens may cause meningitis with symptoms similar to those of meningococcal meningitis (including a petechial rash), an antibiotic active against the common causes of meningitis is preferable. These include Streptococcus pneumoniae and H. influenzae type b. The immediate treatment of choice is therefore ceftriaxone, administered intravenously in one dose (see Box 2). Alternatively, intravenous cefotaxime may be used. Neither is available as an emergency ("doctor's bag") drug in Australia.

Benzylpenicillin is available as a doctor's bag drug and should be used when ceftriaxone and cefotaxime are unavailable. If benzylpenicillin is not available, ampicillin or amoxycillin may be used, and when penicillin and third generation cephalosporins are contraindicated (e.g., because of hypersensitivity) chloramphenicol is also an alternative.

All antibiotics should be given intravenously, unless intravenous access cannot be obtained. While an intravenous cannula is desirable, the dose can be given via a steel or "butterfly" needle. Intramuscular administration is not desirable, as supervening shock and hypotension may impair absorption of the injected antibiotics.  

Hospital therapy

Antibiotic treatment: There should be no delay in starting or continuing treatment after hospital admission. Initial hospital therapy should be with ceftriaxone or cefotaxime, usually with benzylpenicillin.24 Therapy can then be modified depending on culture and sensitivity results. It should be continued for at least five days and, if meningitis is proven or probable, for at least five days after resolution of fever.

Preventing transmission: Respiratory isolation of the patient is recommended for 24 hours after starting chemotherapy. The patient should also be given rifampicin before discharge if treatment did not include an antibiotic, such as ceftriaxone, that eradicates nasopharyngeal carriage of N. meningitidis .  

Diagnostic tests

 Therapy should not be delayed while awaiting results of diagnostic tests (such as computed tomography). Diagnosis of meningococcal disease is confirmed by isolation of N. meningitidis or detection of gram-negative diplococci or meningococcal antigen in cerebrospinal fluid, blood or another normally sterile site. Therefore, all patients with suspected meningococcal infection should have the following specimens taken and investigations after arrival at hospital:
  • A blood sample taken as soon as possible for culture.
  • A blood sample for neutrophil and platelet counts and, if petechiae or frank bleeding are evident, for formal coagulation studies.
  • Gram-stained smears and culture from purpuric or other skin lesions, which may be helpful in confirming the diagnosis.
  • Cerebrospinal fluid, collected by lumbar puncture, for microscopy and culture. Although once the mainstay of diagnosis, collection of cerebrospinal fluid may need to be deferred because of the association between meningitis and raised intracranial pressure, cerebral oedema, general or focal swelling and mass lesions, such as abscesses. For example, if there is evidence of raised intracranial pressure (e.g., clouded or impaired consciousness, papilloedema, focal neurological signs or vomiting), lumbar puncture should be deferred until therapy and supportive measures have been established and investigations such as computed tomography performed to define intracranial lesions. The patient's coagulation status should also be considered before lumbar puncture owing to the risk of haemorrhage with concomitant coagulopathy.
  • A throat swab for culture. Its value is controversial, but in a patient who has received prior antibiotics this may be the only site from which N. meningitidis can be isolated.
  • Other investigations, such as chest x-rays, electrolyte and acid-base studies, when clinically indicated.

With the emphasis on antibiotic therapy before hospital admission, opportunities to prove a diagnosis by culture may decrease, increasing the importance of other diagnostic tests. Urinary antigen tests, while not helpful in diagnosing meningococcal disease because of low sensitivity and specificity, may be helpful if another organism is responsible, such as H. infuenzae type b and group B streptococci. Use of polymerase chain reaction to detect meningococcal DNA in cerebrospinal fluid and, more recently, in peripheral blood can increase the number of proven cases.25 However, this technique is still under development and not widely available. Serological tests of acute and convalescent blood showing a rising antibody titre may be of value in confirming the diagnosis retrospectively.  

Characterising Neisseria meningitidis

Characterising isolates of N. meningitidis is not necessary for clinical management, but is indispensable for identifying and managing clusters and outbreaks of disease, and for following trends in the epidemiology of the disease. Therefore, every isolate of N. meningitidis should be characterised. This should be done urgently when an outbreak is suspected. Otherwise, isolates can be batched together for routine characterisation at about monthly intervals. Laboratories associated with the National Neisseria Network in each State or Territory can arrange testing for the serogroup, serotype and subtype of meningococcal isolates and for antibiotic sensitivities.16 They can also advise on availability of genetic and electrophoretic typing.  

Management of contacts

 Close contacts of patients with invasive meningococcal disease are at increased risk, including household members, dormitory contacts, staff and children in childcare facilities and those directly exposed to the patient's oral secretions (e.g., by mouth kissing, sharing food and drinks and performing mouth-to-mouth resuscitation). Health staff who provide clinical care but do not perform mouth-to-mouth resuscitation and are not involved with intubation are not at increased risk of disease, nor are classroom and casual contacts of a sporadic case.

The risk of disease among close contacts can be reduced by chemoprophylaxis as soon as possible with rifampicin (10 mg/kg in children, to a maximum of 600 mg; and 600 mg in adults), twelve-hourly for two days.17 Alternative antibiotics include: ceftriaxone as a single intramuscular dose of 5 mg/kg, to a maximum of 250 mg (reduced to 125 mg in children under 15 years of age, and contraindicated in infants below six weeks of age), or ciprofloxacin 500 mg as a single oral dose (contraindicated in children under 12 years of age, people weighing less than 40 kg and pregnant women).  

Identification and management of an outbreak

 An outbreak of meningococcal disease is a public health crisis that calls for a rapid, coordinated public health response. Changes that suggest an outbreak is evolving include:6,13,16,26

  • Clustering of cases within an age or social group;
  • Shift in disease from children under five years to older children and adolescents; and
  • Phenotypic and genetic similarity among the strains causing disease.
When an outbreak is caused by a vaccine-preventable strain, vaccination of people at risk should be considered. The decision will usually be complicated by the relatively small number of cases in the community and the high cost of vaccine. The decision-making process should therefore include firm confirmation of the outbreak, identification of the specific population at risk, estimation of the magnitude of risk26 and consideration of the level of community concern.

The criteria for considering vaccination are:

  • In a community setting, three or more cases of the same vaccine-preventable strain within three months in a defined population, where the attack rate exceeds 10/100 000 population.
  • In institutions, such as schools or universities, two or more cases of the same vaccine-preventable strain occurring within a three-month period.
    When determining the number of cases for this purpose, secondary cases should not be included, as they represent the high risk of disease among close contacts rather than population risk.20
  • In Aboriginal communities, outbreaks of serogroup A and C meningococcal disease are of particular concern,11,13,15,16 and it is advisable to use vaccine earlier in such circumstances. In a remote Aboriginal community, two cases within five days has been used as an indication for a community-wide vaccination program.15  

Public concern

 News of a child with fulminating meningococcal disease, or of outbreaks in schools, other institutions or the community, causes public anxiety and is rapidly taken up by the media. It is important to be proactive in informing the community and general practitioners about the outbreak and planned control measures, particularly if they include a vaccination campaign. The greatest challenge is to have cooperation from the media, so that they support initiatives to control the disease and do not generate unnecessary discord or controversy.

Specific guidelines for informing the public and medical profession have been published elsewhere.27 In addition, the NHMRC guidelines describe a communication strategy and provide an information sheet on symptoms of the disease for lay people, sample letters for parents of children who may have been in contact with a patient, bulletins for health professionals and sample media releases.7 During outbreaks, public health units should consider setting up a telephone hotline for enquiries from the public and general practitioners. Politicians at local and State levels should also be kept informed about the course and management of an outbreak.  

Acknowledgements

 We acknowledge the excellent assistance provided by the secretariat of the Working Party in developing the guidelines, including Jenny Hargreaves, Barbara Sheppard, Evon Bowler and Leona Seib. Dr Jeff Hanna was a member of the NHMRC Working Party up to the stage it developed the draft guidelines.  

References
  1. Caugant DA, Froholm LO, Bovre K, et al. Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease. Proc Natl Acad Sci U S A 1986; 83: 4927-4931.
  2. Lystad A, Aasen S. The epidemiology of meningococcal disease in Norway 1975-91. Natl Inst Pub Health (Norway) Ann 1991; 14: 57-65.
  3. Whalen CM, Hockin JC, Ryan A, Ashton F. The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis . JAMA 1995; 273: 390-394.
  4. Jackson LA, Schuchat A, Reeves MW, Wenger JD. Serogroup C meningococcal outbreaks in the United States. An emerging threat. JAMA 1995; 273: 383-389.
  5. Serogroup B meningococcal disease--Oregon, 1994 [editorial]. MMWR Morb Mortal Wkly Rep 1995; 44: 121-124.
  6. Munro R, Kociuba K, Jelfs J, et al. Meningococcal disease in urban south western Sydney, 1990-1994. Aust N Z J Med 1996; 26: 526-532.
  7. National Health and Medical Research Council. Guidelines for the control of meningococcal disease in Australia. Canberra: AGPS, 1997.
  8. Clements DA, Gilbert GL. Increase in admissions for Neisseria meningitidis infection in Australia [letter]. Lancet 1989; 2: 1464.
  9. Levy M, Manning W, Rubin G. Bacterial meningitis makes a comeback. NSW Pub Health Bull 1991; 2: 5,9-10.
  10. Hargreaves J. Meningococcal infection -- national notifiable diseases data. Commun Dis Intell 1992; 16: 31-35.
  11. Patel MS, Merianos A, Hanna JN, et al. Epidemic meningococcal meningitis in central Australia, 1987-1991. Med J Aust 1993; 158: 336-340.
  12. Watson C, Gill J. Further cases of invasive meningococcal infection in the Katanning area of Western Australia. Commun Dis Intell 1990; 20: 12-13.
  13. Pearce M, Sheridan J, Jones D, et al. Control of group C meningococcal disease in Australian Aboriginal children by mass rifampicin chemoprophylaxis and vaccination. Lancet 1995; 346: 20-23.
  14. Chant K, Stewart G, Brown J, et al. A cluster of meningococcal cases in Campbelltown. NSW Pub Health Bull 1992; 3: 93-94.
  15. Hanna J, Alexander D. Invasive meningococcal disease in an Aboriginal community in north Queensland. Commun Dis Intell 1994; 18: 8-9.
  16. Hanna J, McCall B, Murphy D. Invasive meningococcal disease in north Queensland, 1990-1994. Commun Dis Intell 1996; 20: 320-324.
  17. National Neisseria Network. Meningococcal isolate surveillance, Australia, 1995. Commun Dis Intell 1996; 20: 422-424.
  18. National Health and Medical Research Council. The Australian immunisation procedures handbook. 5th ed. Canberra: AGPS, 1994.
  19. Twumasi PA, Kumah S, Leach A, et al. A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. J Infect Dis 1995; 171: 632-638.
  20. Herbert MA, Heath PT, Mayon-White RT. Meningococcal vaccines for the United Kingdom. Commun Dis Rep CDR Rev 1995; 5: R130-R135.
  21. Poolman JT. Development of a meningococcal vaccine. Infect Agents Dis 1995; 4: 13-28.
  22. Strang JR, Pugh EJ. Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. BMJ 1992; 305: 141-143.
  23. Tunkel AR, Scheld WM. Acute bacterial meningitis. Lancet 1995; 346: 1675-1680.
  24. Antibiotic Guidelines Subcommittee of the Victorian Drug Usage Advisory Committee. Antibiotic guidelines. 9th ed. Melbourne: Victoria Medical Postgraduate Foundation Inc., 1996.
  25. Kaczmarski EB, Borrow R, Gray SJ, et al. Optimising ascertainment of meningococcal infection in England and Wales. In: Zollinger W, Frasch C, Deal C, editors. Abstracts of the Tenth International Pathogenic Neisseria Conference; 1996 Sep 8-13; Baltimore: 475-476.
  26. Wenger JD, Jackson LA, Raj P, Tonelli MJ. Issues in the control of outbreaks of group C meningococcal disease in the United States. Infect Dis Clin Pract 1994; 3: 136-140.
  27. Watson C. Public communication during an outbreak of infectious disease. NSW Pub Health Bull 1993; 4: 73-74.
(Received 18 Nov 1996, accepted 14 Mar 1997)  

Authors' details

Meningococcal Disease Working Party of the National Health and Medical Research Council, Canberra, ACT.
Mahomed S Patel, FRACP, FAFPHM, Fellow, National Centre for Epidemiology and Population Health, Australian National University, Canberra;
Peter J Collignon, FRACP, FRCPA, FASM, Infectious Diseases Physician and Microbiologist, Canberra Clinical School, Canberra Hospital, ACT;
Charles R Watson, MD, FAFPHM, Chair; and Professor of Public Health and Dean of the Faculty of Health and Behavioural Sciences, University of Wollongong, NSW;
Robert J Condon, MApplEpid, FAFPHM, Senior Medical Officer, Royal Flying Doctor Service of Australia, Western Operations, Jandakot, WA;
Richard R Doherty, FRACP, Professor of Paediatrics and Head of Paediatric Medicine, Department of Paediatrics, Monash Medical Centre, Melbourne, VIC;
Angela Merianos, MApplEpid, FAFPHM, Head, Immunisation and Surveillance Section, Disease Control, Territory Health Services, Darwin, NT;
Gregory J Stewart, FRACMA, FAFPHM, Director of Health Services, Central Sydney Area Health Services, Camperdown, NSW.

No reprints will be available from the authors.
Correspondence: Dr M S Patel, National Centre for Epidemiology and Population Health, Australian National University, Canberra 0200.
E-mail: msp868 @ nceph.anu.edu.au

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