Volume 166 Issue 11

What are the risks of diagnostic medical radiation? Richard C Smart It is both ethically and economically desirable to restrict the use of diagnostic medical radiation to only those who will benefit from it. However, patients should not refuse diagnostic tests based on an exaggerated estimation of the risks because most of these tests involve low doses of radiation. It is probable that the risks derived from studies of the atomic bomb survivors, who were exposed to high doses of radiation, overestimate the risks at low doses. No evidence of thyroid cancer, leukaemia or non-Hodgkin's lymphoma has been found in patients exposed to diagnostic levels of ionising radiation. For most diagnostic tests, the risks arising from the radiation exposure are too small to be observed and the benefits will almost always outweigh the risk. (MJA 1997; 166: 589-591) Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - The effect of dose - The effects of dose rate and fractionation - The effects of age at radiation exposure - Risks of medical diagnostic tests - Risks from natural background radiation - Risks to children from parental radiation exposure - Conclusion - References - Authors' details Register to be notified of new articles by e-mail - Current contents list - (c)MJA1997 Introduction Recently in this Journal, Roebuck suggested that, for many diagnostic radiology and nuclear medicine investigations, the risk from the ionising radiation may outweigh the benefits of these tests.1He outlined steps which referring doctors and radiologists may consider to reduce patient irradiation, and strongly advocated better education of the medical profession as to the risks of diagnostic radiation. However, Roebuck's estimates of the number of radiation-linked fatal malignancies in Australia each year must be questioned because these data were based on the risk of radiation-associated deaths determined from studies of the survivors of the 1945 atomic bombing of Hiroshima and Nagasaki. Many were exposed to radiation doses hundreds of times greater than those encountered in medical diagnostic procedures.2Most medical diagnostic studies result in effective doses in the range 1-20 mSv, although chest x-rays give only 0.05 mSv. There is increasing evidence that the risk associated with medical diagnostic radiation exposure is substantially less than that predicted from studies of high-dose radiation. The effect of dose The effects of radiation at high doses are dependent on the administered dose.3Solid tumours show a linear incidence with dose, while leukaemia (chronic and acute myelogenous, and acute lymphocytic) shows a linear-quadratic dose-response function (Figure, below).4In both cases, the dose-response curve flattens off at high doses (> 3 Sv), probably a direct effect of cell death. This does not necessarily imply that such a relationship continues to zero dose -- the basis of the "linear no-threshold hypothesis", which purports that any dose of radiation carries a risk. An alternative hypothesis is that there is no risk up to a certain dose but that the risk increases above this threshold; another hypothesis (commonly known as "radiation hormesis") proposes that there is a reduced risk for low levels of radiation and a higher risk at higher doses. The Hiroshima and Nagasaki survivor data showed no increase in the risk of leukaemia at low radiation doses (range, 0-200 mSv).4For solid tumours, the lowest radiation dose at which there was a statistically significant excess risk was 50 mSv,4a level well above that of most diagnostic radiological testing. The effects of dose rate and fractionation The atomic bomb survivors received all their radiation over a short period of time, and thus at high dose rates, while medical diagnostic radiation is given at low dose rates. How does dose rate affect the consequences of radiation exposure? Animal studies have shown a reduction in effect of between two and five for life-shortening and between one and 10 for tumour induction when the same total dose was given at a significantly lower dose rate.3What happens if the total dose is delivered in a number of smaller doses spread over a prolonged time period (fractionated), such as would be received by a patient having a series of diagnostic x-rays? In the past, patients with tuberculosis were monitored with fluoroscopy every two weeks over a five-year period and hence received a substantial amount of radiation (average lung dose, 840 mGy). In one United States study, there was no evidence of an increased risk of lung cancer in a cohort of such patients (standardised mortality ratio, 0.8).5However, other studies have shown an increase in breast cancer similar to that found in Hiroshima and Nagasaki survivors.6,7The risk varied with the total dose received. For those receiving a dose of 1-2 Sv, the relative risk (RR) of breast cancer was 1.38 (95% confidence interval [95% CI], 1.07-1.77), whereas for those receiving a dose of 0.5-0.9 Sv the RR was 1.11 (95% CI, 0.86-1.43).7 The United Nations Scientific Committee on the Effects of Atomic Radiation suggested a dose and dose rate effectiveness factor (DDREF) of 2.0 for leukaemia and 1.4 for other cancers.3The DDREF is a factor applied to the risk from the radiation observed in the high-dose atomic bomb studies to predict the risk from radiation observed in low-dose and low-dose-rate studies. The Committee stated that the DDREF should be applied if the total dose is less than 200 mGy or the dose rate is below 0.1 mGy/min, as is typically found in diagnostic x-ray studies.3 The effects of age at radiation exposure The most recent report on the mortality of the atomic bomb survivors (which includes an extended period of follow-up until 1990 and which includes an additional 10 500 survivors) provides estimates of excess risk specific to sex and age at exposure.4 Those exposed at age 50 had one-third of the lifetime risk per Sv for solid cancers as those exposed at age 30. Those exposed in childhood had 1-1.8 times the estimates for those aged 30.4The excess lifetime risk of leukaemia for those exposed at age 50 was about two-thirds of the risk if exposed at an earlier age.4Similarly, the Canadian studies on breast cancer following extended monitoring of treatment with fluoroscopy for tuberculosis found that the excess relative risk (ERR) decreased with increasing age at exposure.7Women exposed at age 50 or more showed no increase in breast cancer, while an ERR of 1.25 per Sv was found for those irradiated between birth and nine years. Risks of medical diagnostic tests Several recent studies have investigated the cancer risk in patients who had received diagnostic x-ray procedures. Inskip et al. identified all patients with papillary and follicular thyroid carcinoma diagnosed between 1980 and 1992 in Uppsala, Sweden.8 An equal number of control patients were matched for age, sex and country of residence. The case patients' hospital medical records were examined and the number and type of x-rays were recorded. Radiation received three to five years before diagnosis was excluded because of the known latent period for thyroid cancers. They found that each of the 484 case patients had received an average of 6.1 x-ray procedures, while the control patients received an average of 6.6 procedures; a similar number in each group received no x-rays (115 and 117, respectively). No association was found between higher doses to the thyroid and cancer, and there was no change in the relative risk with thyroid doses up to the highest dose of 80 mGy. Iodine 131 (I 131) has long been used for the diagnosis and treatment of thyroid disorders. Hall et al. recently reported on the risk of thyroid cancer in 34 104 patients given diagnostic doses of I 131 of between 0.04-37 MBq.9An excess of thyroid cancers was observed only among patients referred for a suspected thyroid cancer. No increase was seen among the 23 319 patients referred for other reasons. In a 1991 United States study, all x-ray procedures were reviewed for 565 patients with all types of leukaemia, 318 patients with non-Hodgkin's lymphoma and 208 patients with multiple myeloma.10The case patients were selected from a prepaid health plan in Oregon and California from 1956 to 1982 and were matched to 1390 control patients. The probable bone marrow dose was assigned for each x-ray and a cumulative bone marrow dose was estimated for each case patient. A latent period of four years was assumed for both leukaemia and solid tumours. A similar number of case and control patients had not had any x-rays during that time. The average number of x-rays was identical in both groups (11.6). The incidence of leukaemia in the irradiated patients was not significantly increased compared with those who had not been irradiated and there was no evidence of an increased risk with increasing dose (RR, 1.13; 95% CI, 0.7-1.8). Similarly, there were no significant increases in RRs for non-Hodgkin's lymphoma (RR, 1.24; 95% CI, 0.80-2.0) or for multiple myeloma (RR, 1.07; 95% CI, 0.6-2.0). The only group showing any possible effects of the radiation was a small group who had received the highest number of x-rays (average of 35) and who had an RR of 4.5 for multiple myeloma. Although these studies yielded negative results, they do not imply zero risk from diagnostic medical radiation but suggest that the risk is very small. Further studies involving large numbers of patients are required to detect the low levels of risk at these low doses. Risks from natural background radiation People are continuously exposed to natural background radiation (e.g., cosmic radiation, terrestrial radiation sources such as soils and building materials, and radon gas). The level of background radiation varies substantially around the world and has provided an alternative means of assessing the risks of low doses of radiation. One study involved 80 000 individuals living in two adjacent regions in China where the levels of background radiation differed by more than a factor of two.11The leukaemia mortality data indicated that there was no increasing risk with dose; if anything, there was a decreasing risk with dose. The average background radiation at sea level in Australia has been estimated to be 2.1 mSv per annum.12Therefore, a patient having a chest x-ray receives the same effective dose as he or she would receive naturally in only six days. Risks to children from parental radiation exposure The Oxford Survey of Childhood Cancers has estimated that the absolute risk of mortality from cancer following radiation exposure in utero is 1 in 20 000 per mSv.13 Data from the atomic bomb survivors indicate an increased risk of mental retardation to the fetus if the mother is exposed to radiation between eight to 25 weeks' gestation.2During the most sensitive period (eight to 15 weeks' gestation), there may be a reduction in IQ of 0.03 units per mSv.2There is no apparent increased risk of congenital malformation below a dose of 100 mSv.14The possible association of childhood cancer with paternal irradiation has also recently been investigated by the Oxford Survey of Childhood Cancers.15Using data from 14 869 children dying from cancer in the United Kingdom in the period 1953-1981 matched to an equal number of control patients, paternal irradiation before conception was found not to be a risk factor for childhood leukaemia. Gardner et al. suggested that there was a risk of childhood cancer following irradiation of the father before conception.15 They investigated a cluster of cases of childhood leukaemia and lymphoma observed in the vicinity of the Seascale nuclear processing plant in the United Kingdom and suggested an association between these cases and external irradiation of the father, particularly in the six months before conception. There have been many attempts to reproduce this finding in France, Germany, Canada and the United States, but none of these studies found a similar association.17Furthermore, clusters of leukaemia were observed at six potential nuclear sites in the United Kingdom and two nuclear installations that had been built but not operated.18As no increased levels of radiation existed at these sites, it was apparent that radiation exposure was not the cause of these clusters. Conclusion It is both ethically and economically desirable to restrict the use of diagnostic radiation to only those who will benefit from it. Wherever possible, diagnostic procedures which do not use ionising radiation should be used if these alternative techniques can give the same information. However, when a radiological study is clinically indicated it is equally important that patients do not refuse such tests based on an exaggerated estimation of the risks. For example, about 2400 women die of breast cancer in Australia each year.19Periodic mammographic screening of women over the age of 50 has been shown to reduce breast cancer mortality by 30%.20In the most recent report of the Canadian Breast Cancer Study, Howe and McLaughlin concluded that "even a very small benefit to women from routine mammographic screening would outweigh any possible risks of radiation-induced breast cancer".7If diagnostic radiation studies are used appropriately, with all routine steps taken to minimise patient radiation exposure,1the benefits will almost always outweigh the risk. References Roebuck DJ. Ionising radiation in diagnosis: do the risks outweigh the benefits? Med J Aust 1996; 164: 743-747. International Commission on Radiological Protection. 1990 Recommendations of the International Commission on Radiological Protection. (ICRP Publication 60.) Oxford: Pergamon Press, 1991. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Sources and effects of ionizing radiation, Annex A. Epidemiological studies of radiation carcinogenesis. 1994 Report. New York: UNSCEAR, 1994. Pierce DA, Shimizu Y, Preston DL, et al. Studies of the mortality of atomic bomb survivors. Report 12, Part 1. Cancer: 1950-1990. Radiat Res 1996; 146: 1-27. Davis FG, Boice JD Jr, Hrubec Z, et al. Cancer mortality in a radiation-exposed cohort of Massachusetts tuberculosis patients. Cancer Res 1989; 49: 6130-6136. Boice JD Jr, Preston DL, Davis FG, et al. Frequent chest x-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Radiat Res 1990; 125: 214-222. Howe GR, McLaughlin J. Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer mortality in the atomic bomb survivors study. Radiat Res 1996; 145: 694-707. Inskip PD, Ekbom A, Galanti MR, et al. Medical diagnostic x-rays and thyroid cancer. J Natl Cancer Inst 1995; 87: 1613-1621. Hall P, Mattsson A, Boice JD Jr. Thyroid cancer after diagnostic administration of iodine-131. Radiat Res 1996; 145: 86-92. Boice JD Jr, Morin MM, Glass AG, et al. Diagnostic x-ray procedures and risk of leukaemia, lymphoma and multiple myeloma. JAMA 1991; 265: 1290-1294. Wei L, Zha Y, Tao Z, et al. Epidemiological investigation of radiological effects in high background radiation areas of Yangjiang, China . J Radiat Res 1990; 31: 19-136. Costello JM. Radioactivity in the environment. Radiat Prot Aust 1983; 1: 21-27. Mole RH. Childhood cancer after prenatal exposure to diagnostic x-ray examinations in Britain. Br J Cancer 1990; 62: 152-168. Mettler FA, Moseley RD. Medical effects of ionizing radiation. Grune & Stratton, 1985. Sorahan T, Lancashire RJ, Temperton DH, Heighway WP. Childhood cancer and paternal exposure to ionizing radiation: A second report from the Oxford Survey of Childhood Cancers. Am J Ind Med 1995; 28: 71-78. Gardner MJ, Snee MT, Hall AJ, et al. Results of a case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ 1990; 300: 423-429. McLaughlin JR, Clarke EA, Nishri D, et al. Childhood leukaemia in the vicinity of Canadian nuclear facilities. Cancer Causes Control 1993; 4: 51-58. Cook-Mozaffari P, Darby SC, Doll R. Cancer near potential sites of nuclear installations. Lancet 1989; 2: 1145-1147. Australian Institute of Health and Welfare. Cancer in Australia, 1989-90. Canberra: AIHW, 1996. Fletcher SW, Black W, Harris R, et al. Report of the International Workshop on Screening for Breast Cancer. J Natl Cancer Inst 1993; 85: 1644-1656. Authors' details Department of Nuclear Medicine, St George Hospital, Kogarah, NSW. Richard C Smart, MSc, PhD, Principal Medical Physicist. Reprints: Dr R C Smart, Department of Nuclear Medicine, St George Hospital, Kogarah, NSW 2217. E-mail: r.smart @ unsw.edu.au ©MJA 1997 <URL: http://www.mja.com.au/> (c) 1997 Medical Journal of Australia.

Richard C Smart

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) Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - Epidemiology - Vaccines - Patient management - Management of contacts - Identification and management of an outbreak - Acknowledgements - References - Authors' details - ©MJA1997 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 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. Lystad A, Aasen S. The epidemiology of meningococcal disease in Norway 1975-91. Natl Inst Pub Health (Norway) Ann 1991; 14: 57-65. 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. Jackson LA, Schuchat A, Reeves MW, Wenger JD. Serogroup C meningococcal outbreaks in the United States. An emerging threat. JAMA 1995; 273: 383-389. Serogroup B meningococcal disease--Oregon, 1994 [editorial]. MMWR Morb Mortal Wkly Rep 1995; 44: 121-124. 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. National Health and Medical Research Council. Guidelines for the control of meningococcal disease in Australia. Canberra: AGPS, 1997. Clements DA, Gilbert GL. Increase in admissions for Neisseria meningitidis infection in Australia [letter]. Lancet 1989; 2: 1464. Levy M, Manning W, Rubin G. Bacterial meningitis makes a comeback. NSW Pub Health Bull 1991; 2: 5,9-10. Hargreaves J. Meningococcal infection -- national notifiable diseases data. Commun Dis Intell 1992; 16: 31-35. Patel MS, Merianos A, Hanna JN, et al. Epidemic meningococcal meningitis in central Australia, 1987-1991. Med J Aust 1993; 158: 336-340. Watson C, Gill J. Further cases of invasive meningococcal infection in the Katanning area of Western Australia. Commun Dis Intell 1990; 20: 12-13. 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. Chant K, Stewart G, Brown J, et al. A cluster of meningococcal cases in Campbelltown. NSW Pub Health Bull 1992; 3: 93-94. Hanna J, Alexander D. Invasive meningococcal disease in an Aboriginal community in north Queensland. Commun Dis Intell 1994; 18: 8-9. Hanna J, McCall B, Murphy D. Invasive meningococcal disease in north Queensland, 1990-1994. Commun Dis Intell 1996; 20: 320-324. National Neisseria Network. Meningococcal isolate surveillance, Australia, 1995. Commun Dis Intell 1996; 20: 422-424. National Health and Medical Research Council. The Australian immunisation procedures handbook. 5th ed. Canberra: AGPS, 1994. 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. Herbert MA, Heath PT, Mayon-White RT. Meningococcal vaccines for the United Kingdom. Commun Dis Rep CDR Rev 1995; 5: R130-R135. Poolman JT. Development of a meningococcal vaccine. Infect Agents Dis 1995; 4: 13-28. Strang JR, Pugh EJ. Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. BMJ 1992; 305: 141-143. Tunkel AR, Scheld WM. Acute bacterial meningitis. Lancet 1995; 346: 1675-1680. Antibiotic Guidelines Subcommittee of the Victorian Drug Usage Advisory Committee. Antibiotic guidelines. 9th ed. Melbourne: Victoria Medical Postgraduate Foundation Inc., 1996. 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. 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. 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 ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Mahomed S Patel · Peter J Collignon · Charles R Watson · Robert J Condon · Richard R Doherty · Angela Merianos · Gregory J Stewart