Infectious diseases

To the Editor: In Australia, an estimated 11 000 people become infected with hepatitis C virus (HCV) each year.1 Most are injecting drug users. The Early Hepatitis C Intervention Project was a collaboration between the STD Services Surveillance Unit, Drug and Alcohol Resource Unit and Infectious Diseases Unit at the Royal Adelaide Hospital, Adelaide, South Australia. Its objectives were to manage people who had seroconverted in the preceding 12 months and to provide standard treatments for drug use and dependence. Services included information and education on HCV, referral, counselling, psychosocial support and three-monthly clinical evaluation. The project was approved by the Ethics Committee of the Royal Adelaide Hospital and funded by the Department of Human Services for 18 months. The attendance rate was low. Of 88 people with HCV seroconversion who were identified as eligible for enrolment by the Surveillance Unit (from the mandatory notification scheme), 57 agreed to further contact by mail or telephone, and 12 attended for risk assessment. Of these, eight enrolled in the project (10% of those eligible). Despite demographic variation within the group, similarities included difficulties with accommodation, finances, mental health and social integration. Seven of the eight participants had injecting drug use as the risk factor for HCV infection. Most participants also used alcohol and cannabis. During the program, half decreased their risk-taking behaviour: four reduced injecting drug use, and four reduced alcohol use, reaching low risk levels. Characteristics of participants at their last interview are summarised in the Box. Two participants are maintaining regular contact with the Drug and Alcohol Resource Unit. Despite encouragement, few of the target group engaged in the program. We do not know why so few people who agreed to attend a first appointment failed to do so. We did not have their permission or the resources to contact them again. Maintaining contact with participants also proved challenging, and was in part unsuccessful because of complex, multifaceted social issues aside from HCV infection (Box). These included unstable accommodation, use of health services only when in crisis, mental health problems, financial difficulties, polydrug use and continued risk-taking behaviours despite harm-reduction information. In conclusion, the Australian epidemic of HCV infection, driven by injecting drug use, is likely to continue unless a new approach to harm minimisation is developed. Such an approach will recognise that comorbidities and social dislocation influence risk of infection. Unless treatment programs address coexisting problems, it will be futile to offer definitive treatment for HCV infection.2 Within the limited objectives and resources of this project, we were unable to support these people comprehensively. We believe that a "one-stop shop" that includes active and intensive case management by a flexible, multidisciplinary team and deals with social, economic and mental health issues may be a more effective approach to the care of people with recent HCV infection. Characteristics of participants in the Early Hepatitis C Intervention Project at last interview Place of residence Current mental illness* Attendances Age, sex Employ-ment Polydrug use At 5 nominated appointments Total† IDU change‡ Persistent viraemia‡ 19, F No Yes NFA Yes 3 6 Reduced IDU Yes 21, F Part-time Yes NFA Yes 3 5 Reduced IDU No 21, M No Yes NFA Yes 3 4 No IDU at enrolment Yes 24, M Voluntary No Rental Yes 1 1 Denied IDU ever Yes 30, M Casual Yes NFA No 2 4 No IDU Yes 36, M No Yes Parents Yes 1 4 Unknown Yes 38, M Full-time Yes NFA Yes 2 3 Reduced IDU No 43, M Full-time No Rental Unknown 1 1 Unknown No IDU = injecting drug use. NFA = no fixed abode. * Mainly depression, anxiety and personality disorder. † Includes self-initiated visits. ‡ Determined by polymerase chain reaction.

To the Editor: Reactions to insect bites are unpleasant and can be dangerous.1 Kumar2 commented that people who react to mosquito bites with local itching and inflammation appeared less likely to develop malaria than those with no reaction. In a later personal communication, he gave me unpublished data showing an inverse linear relationship between the severity of the reaction to mosquito bites and the incidence of clinical malaria. Ross River virus infection is endemic in all Australian states. A specific serological test is available to confirm suspicious clinical illnesses. Some people have serological signs of past infection without any history of clinical disease. With Kumar's findings in mind, I asked people with a past history of clinical Ross River virus infection, proven by serology, whether they reacted to mosquito bites. All seven asked said that they had had no reaction. Their main complaint was the noise made by predatory mosquitoes. I then asked patients who were in the same age range and general social class, who lived in the same area and were attending clinics with other diseases, whether they had had any clinical illness diagnosed as Ross River virus infection. Of the 18 asked, none had had the clinical disease or serological tests for the disease. All 18 had moderate to severe reactions and itching with mosquito bites. The Box shows these results Fisher's exact test gives the probability of this finding as 0.0000003. These observations have not explored all aspects of the problem, so this level of probability may be optimistic, but, even so, it makes pointless any further informal collection of data. These findings justify a formal epidemiological study, including antibody titres. It should include those who react to mosquito bites and those who do not, and those with and without a past history of the clinical illness. This informal study suggests that reactions to mosquito bites protect against Ross River virus infection, and parallels Kumar's findings in malaria. There may be behavioural and biological explanations for this finding. People who itch with mosquito bites may take greater precautions to avoid them. Conversely, people who do not itch may spend more time outdoors and be more likely to be bitten. Biologically, reactions to bites may be examples of a generalised protective effect of local reactions against insect-borne diseases. The inflammatory reaction with itching may be a factor in defence against infection3 by limiting or destroying injected parasites and viruses locally or through a more vigorous generalised response that prevents disease or limits infection to a subclinical level. Investigation of local inflammatory response might provide clues to effective prevention and treatment. Reactions to mosquito bites among people with and without evidence of Ross River virus (RRV) disease No reaction Moderate to severe reaction Past RRV disease 7 0 No past RRV disease 0 18

Alan E Dugdale

Antibiotic resistance is a consequence of antibiotic use — we need to use antibiotics less and to use them prudently. Plans to combat antibiotic resistance were recently proposed by the World Health Organization, a United States interagency taskforce and the Australian Joint Expert Technical Advisory Committee on Antibiotic Resistance. Prudent antibiotic use includes not using antibiotics when benefit is minimal (eg, in many respiratory tract infections), using narrow-spectrum antibiotics whenever possible and using optimal dosages and regimens. The need for antibiotic therapy can be reduced by preventing infections through vaccination, infection control measures and improved sanitation. Surveillance of antibiotic resistance is needed to target interventions for minimising antibiotic use. More research is needed into new antibiotics and regimens and into improving medical devices and protocols to prevent infection.

Series Editors:

To the Editor: The recent editorial by McCarthy and Garrow1 eloquently articulates a case for a coordinated national approach to controlling parasite infections in Aboriginal populations, based predominantly on the authors' experience with chemotherapeutic intervention in one remote community in Western Australia. While sympathetic to their motives, I am not so optimistic about the outcome of their proposal. For 20 years, Queensland maintained a centrally coordinated Aboriginal health program designed to monitor and eradicate parasitic infections. The program, which used targeted chemotherapy as its core strategy, was very successful with regard to intestinal worms, suppressing trichuriasis almost to extinction (unpublished observation) and virtually eradicating hookworm.2 However, the prevalence of gut protozoan infections (such as giardiasis and cryptosporidiosis) was hardly affected, for the obvious reason that these are relatively short-lived and spread directly person-to-person, which means that personal hygiene is much more crucial to their control. Systematic surveillance ceased after the program was dismantled (for political reasons) in 1990, and anecdotal reports since indicate that hookworm is now returning to Queensland. Again, this is not surprising given the mobility of Indigenous people, and the ability of infective larvae of Ancylostoma duodenale, the local hookworm species, to persist in a dormant state in host tissues, where they are refractory to currently available treatment.3 In support of their case, McCarthy and Garrow presented lymphatic filariasis in Australia as but one successful precedent, implying that it was eradicated "through sustained control programs conducted by dedicated public health agencies . . . using effective drugs".1 This is not supported by historical facts; the disease did disappear from endemic areas, but well before effective chemotherapy became available, and for reasons that are still debatable4 (although mosquito suppression, resulting more from general improvements in living conditions with rising community affluence than from any coordinated activity, is the most likely explanation). At the community level, parasitic infections of the gut represent not so much a primary problem as a symptom of a more fundamental societal malaise. They will disappear from Aboriginal communities only with a sustained improvement in living conditions (including nutrition, sanitation and personal hygiene), driven by the people themselves when armed with effective public health knowledge. This is a challenge that continues to dwarf the capabilities of all our governments and politicians, at all levels.

Paul Prociv · Stuart C Garrow · James S McCarthy

In reply: While specific details of control strategies for intestinal parasites vary according to parasite species, available anthelmintic agents and tools for environmental intervention, it is widely accepted that sustained, coordinated programs supported by government, community and health professionals with agreed methods and targets are the key to success.1 Prociv describes the outcome of just such a program for hookworm in Queensland, and the subsequent recrudescence of infection once the program was scrapped. The program in northern Western Australia succeeded because of commitment by government, community involvement entailing community debate and ownership of the program,2 education, and behavioural change, and improvement in public sanitation facilities as well as chemotherapy.3 We believe that a critical determinant of the outcome of our program was the inclusion of the community in designing the program. We agree with Prociv that control of filariasis and malaria was achieved in Australia by mosquito control; our statement about the role of sustained public health programs refers to the control of leprosy.4 With respect to the prospects for control of intestinal protozoa as well as helminths, a single-dose regimen with broad-spectrum activity would be ideal. While albendazole shows some useful clinical activity in giardiasis, single-dose regimens of this drug are insufficient to effect cure, as was observed in our study. While the social and environmental hurdles may appear to "dwarf the capabilities of government", we believe that there is a continuing need for Aboriginal health organisations, health professions and health departments at state and national levels to tackle parasitic infections. The logical approach is to model wider programs on successful local programs, and to avoid drifting into policy and program nihilism.

Stuart C Garrow · James S McCarthy

Malaria remains a global crisis that kills at least one to two million people per year, mainly children in sub-Saharan Africa.1 Forty per cent of the world's population is at risk of malaria, and each year more than 300 million people have episodes of acute malaria. In recent times, there has been a breakdown in malaria control programs. This has been caused by failure of health systems in the poorest countries, as well as the emergence of mosquitoes resistant to insecticides and malaria parasites resistant to cheap, widely available drugs. In addition, population movements, large-scale development projects, civil wars and conflicts, as well as environmental changes, have all acted in concert to increase the number of individuals at risk of malaria. In Papua New Guinea, for example, malaria is the commonest cause of outpatient presentation and accounts for an estimated 27% of all attendances at health facilities.2 In some Papua New Guinea provinces, malaria is the reason for more than 40% of health centre attendances, and equals pneumonia as a primary cause of death.2 In recognition of the need for a renewed attack on malaria, a global strategy for malaria control was presented to a World Health Organization Conference of Health Ministers in 1992.3 The strategy, now incorporated into the Roll Back Malaria Campaign, promoted a new philosophy emphasising malaria control (in contrast to eradication), and acknowledging the need for different approaches to disease control in different populations. For example, the approach to malaria control in children and pregnant women in Africa is different to that in adult refugee populations. The strategy emphasised the importance of political commitment, such as that given by the heads of State and governments of African countries in Nigeria in 2000 (the Abuja Declaration).4 All participants resolved to commit to an intensive effort to reduce the burden of malaria by strengthening health systems, implementing action plans, improving local capacity, promoting early recognition and treatment of clinical malaria, and reinforcing efficacious preventive measures such as the use of impregnated bednets and chemoprophylaxis. An important component of the strategy is the development of new antimalarial drugs and vaccines. Vaccines have been shown to be one of medicine's most cost-effective interventions. A malaria vaccine that protects for one to five years with 50% efficacy could substantially reduce all-cause child mortality in endemic areas. The cost of such an intervention compares very well with that of using insecticide-treated bednets, and is likely to have major economic as well as social benefits for the populations currently threatened by malaria. An "experiment of nature" suggests that developing a vaccine should be possible. Although many children die of malaria, the majority survive the life-threatening risk of the first few years of exposure and develop clinical immunity. Provided they continue to be exposed to malaria, this immunity protects them from severe disease for the rest of their lives, except during pregnancy. Unfortunately, the immune response that correlates with protection in these lifelong residents of endemic areas has not been identified, so development of a vaccine that mimics this immunity will be difficult. Moreover, malarial parasites demonstrate extreme antigenic diversity. Recent developments, including better methods for antigen production, improved adjuvants and novel delivery systems, provide optimism that sustained and appropriate long-lived immunity can be achieved. Vaccines could be directed against the sporozoite stage of the malaria parasite to prevent infection, or against the stages in human blood — the asexual stage to prevent clinical disease, or the sexual stage to prevent transmission. The malaria vaccine which has been studied in most detail is designed to induce immunity to the sporozoite and the infected liver cell (ie, to stop sporozoites invading liver cells and to kill sporozoite-infected liver cells). In early studies it was shown to induce protective immunity against experimental challenge.5 Under conditions of natural exposure (in semi-immune adult men in The Gambia),6 the vaccine was shown to be safe and well tolerated, with an estimated efficacy (decrease in malaria infection) of 70% in the first nine weeks of follow-up. However, over the 15 weeks of observation, the efficacy fell to 34%. Further trials will determine whether improved efficacy can be achieved in young children. Australian research efforts have led to a multicomponent recombinant protein vaccine targeting the asexual blood stages. This vaccine was tested recently by the Papua New Guinea Institute of Medical Research and its collaborators. The vaccine caused a 62% reduction in parasite density in children, without any harmful side effects.7 Further development will be necessary to produce a vaccine sufficiently efficacious for routine use. In the past there has been a serious lack of funding for research into malaria, partly because companies engaging in this type of research did not expect it to be profitable. A major change has occurred of late, with increased funding from the Wellcome Trust in the United Kingdom, and from the United States through the National Institutes of Health. A grant from the Bill and Melinda Gates Foundation has funded the Malaria Vaccine Initiative of the Program for Appropriate Technology in Health (PATH) (http://www.malariavaccine.org). This worldwide initiative has the specific goal of enhancing the transition of the many promising candidate vaccines from the laboratory to "proof of principle" research in phase I clinical trials. It has funded Australian projects developing vaccines from asexual stage (merozoite) antigens by researchers at Monash University, La Trobe University and the Queensland Institute for Medical Research, partnered by Biotech Australia (New South Wales), the Cooperative Research Centre for Vaccine Technology (Queensland) and Progen Industries Limited (Queensland).8 There are still many challenges in developing a malaria vaccine, such as the need to cope with diverse antigenic types and the importance of stimulating a lifelong response that is boosted by natural infection. Vaccine-induced sterilising immunity that is not boosted by exposure to malaria could put an individual at increased risk when the vaccine-induced immunity wanes. Most importantly, we need vaccines that can be incorporated into national immunisation programs as part of a coordinated, holistic approach to malaria control. Research to find new methods for vector control and new drugs must also continue, as we know from past antimalarial campaigns that a single technology will not be sufficient to control this devastating disease.

Graham V Brown PhD, FRACP · John C Reeder PhD

Hollywood celebrity Pamela Anderson's announcement that she has hepatitis C was a major talking point at this recent conference. Unlike similar announcements of HIV infection, Ms Anderson has not positioned herself as a celebrity campaigner — there is no princess or pop star championing the rights of people with hepatitis C or demanding extra funding for research or services. Hepatitis C has been characterised as an "epidemic of difference",1 affecting people from a wide variety of ethnic, cultural and class backgrounds, with implications for the ability of people with hepatitis C to organise and advocate for changes in policy to improve their lives. Until recently, a study by Crofts et al (1997) was the only example of academic research to focus on hepatitis C-related discrimination and to highlight the part played by healthcare professionals.2 It is timely that many presentations from the recent Third Australasian Conference on Hepatitis C, held in Melbourne in March 2002, highlighted the discriminatory attitudes and practices of some healthcare workers when treating and working among people with hepatitis C. Presentations discussed both institutional and interpersonal discrimination against people with hepatitis C. The relatively low level of community and government concern regarding this epidemic was alluded to in several presentations, suggesting a form of systemic discrimination. There have been more than 160 000 notified cases of hepatitis C since antibody testing became available in 1990.3 Alex Wodak (Director, Alcohol and Drug Service, St Vincent's Hospital, Sydney) described the estimated incidence of 16 000 new infections in 2001 as one every 33 minutes.4 Given the high prevalence and estimated incidence of the hepatitis C epidemic, Nick Crofts (Head, Epidemiology and Social Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health [Burnet Institute], Melbourne) questioned whether the government response might have been quicker and better funded if hepatitis C primarily affected people other than injecting drug users.5 Similarly, conference presentations from people with hepatitis C, community organisations and researchers challenged the positioning of hepatitis C (in their view) as a "second-class" disease. These presentations indicated that people with hepatitis C are tainted as past or current drug users and suffer attitudes of blame from healthcare professionals, often described as "userphobia". Grant McNally (Chair, United Kingdom Assembly on Hepatitis C) summarised the effects of these negative attitudes on people with hepatitis C: they take for granted and come to expect substandard levels of healthcare.6 Academic presentations documented the effects of discrimination on prevention, testing, living with hepatitis C, quality of life, treatment and prognosis. A paper by Michael Kerger (Manager, Centre for Harm Reduction, Burnet Institute), Campbell Aitken (Research Fellow, Centre for Harm Reduction, Burnet Institute) and Nick Crofts discussed piloting peer-delivered hepatitis C testing and counselling at a needle and syringe program.7 The authors highlighted current injecting drug users' fear of discrimination following disclosure of their injecting status to doctors. This fear meant that users often did not present for hepatitis C testing. Max Hopwood (Senior Research Officer, National Centre in HIV Social Research, University of New South Wales, Sydney) and Erica Southgate (Research Fellow, National Centre in HIV Social Research) reported that people with hepatitis C at times feel pressured by healthcare workers to reveal their hepatitis C status.8 They described how some people with hepatitis C were refused medical treatment and had their positive serostatus disclosed to other healthcare workers without permission. Similarly, in discussing women's experiences of living with hepatitis C while using drugs, Mary O'Brien (Researcher, Australian Centre for Research into Sex, Health and Society, La Trobe University, Melbourne)9 reported that participants in their study who were current injecting drug users were treated less favourably by healthcare professionals than women with hepatitis C who were not currently injecting drugs. Sandy Gifford (Professor, School of Health Sciences, Deakin University, Melbourne) presented a paper noting the harmful impact of hepatitis C-related discrimination on participants' quality-of-life measures, including physical and emotional health scores.10 The participation of people from the affected communities provided opportunity for elaboration and reflection on research from the perspective of those primarily affected by hepatitis C. People with hepatitis C spoke informally of feelings of guilt, shame, low self-esteem and self-worth that arose as a result of their interactions with some healthcare professionals. They claimed that internalising stigma led to missed opportunities for care and support from social networks and had implications for people's access to healthcare services. Deb Warneke (Metropolitan Educator, Hepatitis C Council of South Australia) and Richard Hanssens (Representative, Hepatitis C Resource Centre, Christchurch, New Zealand) provided personal views and case studies of the effect of hepatitis C in other domains of life experience —within family circles and the workplace.11,12 These conference papers support the report of the New South Wales Anti-Discrimination Board Enquiry, which found that hepatitis C is a highly stigmatised condition and discrimination is rife, especially in healthcare settings.13 The report states that discrimination results either from an inadequate knowledge of the virus and how it is transmitted, or from a confounding of injecting drug use with hepatitis C virus infection. Both the conference presentations and the Enquiry report acknowledge that not all healthcare workers discriminate against people with hepatitis C. However, it is time for healthcare professionals to acknowledge and address hepatitis C-related discrimination. No short term practical solutions to healthcare workers' discrimination against hepatitis C-positive injecting drug users were proffered. A paper by Piergiorgio Moro (Education and Community Development Officer, Hepatitis C Council of Victoria) suggested that a long term solution would involve organisation and lobbying by the hepatitis C-positive and injecting drug use communities to effect legislative change.14 As implied in many of the conference papers, marginalising people with hepatitis C will impede measures to prevent the further spread of the virus throughout the community, and will contribute much to the burden borne by people with hepatitis C.

Carla J Treloar BSc(Hons), PhD · Max N Hopwood BA(Hons) · Stuart K Loveday BCom

Any new patient with suspected genital herpes should have diagnostic testing with virus identification. Type-specific serological tests that distinguish between antibodies for type 1 and type 2 herpes simplex virus (HSV) may be useful to determine previous exposure but cannot be used to diagnose recurrences of genital herpes. Initial episodes of genital herpes usually require antiviral therapy, while recurrences may be treated with continuous antiviral suppression (if frequent) or episodic therapy; patient counselling and education (including how to recognise lesions) are essential. Topical or systemic therapy is available for initial and recurrent non-genital herpes simplex. Primary varicella infection (chickenpox) and herpes zoster (shingles) are usually diagnosed clinically, but can be confirmed by detection of varicella–zoster virus antigens or nucleic acid from swabs of lesions or by antibody tests. Antiviral therapy should be considered in chickenpox if disease is complicated or the patient is immunocompromised. In herpes zoster, antiviral therapy should be given within 72 hours of onset to patients aged over 50 years or with severe pain or neurological abnormalities to reduce the likelihood and duration of postherpetic neuralgia.

Dominic E Dwyer MD, FRACP, FRCPA · Anthony L Cunningham MD, FRACP, FRCPA

To the Editor: The article on acute community-acquired meningitis and encephalitis by Beaman and Wesselingh1 provides a comprehensive and up-to-date review of diagnostic and management issues relevant to general clinicians. However, the section on vaccines for preventing meningococcal C and pneumococcal diseases is not as contemporary. Contrary to the authors' statements that "a conjugate vaccine covering serogroup C [meningococcus] will be available in Australia shortly", and "a conjugate vaccine [for pneumococcus] is currently under trial in Australia", conjugate vaccines for both diseases are available and registered for use in Australia. Conjugate vaccines have the advantage that they can be used in children from six weeks of age and are expected to provide long-term protection. Meningitec is a meningococcal group C conjugate vaccine approved for use in children from six weeks of age, adolescents and adults. Meningitec has been available from Wyeth Australia since October 2001, but is not part of the National Childhood Immunisation Scheme and, as such, can only be obtained on private prescription at present. Prevenar (pneumococcal septavalent conjugate vaccine) is also approved for use and has been available from Wyeth Australia since January 2001. Prevenar is indicated for active immunisation of infants and children from six weeks to nine years of age against invasive disease, pneumonia and otitis media caused by Streptococcus pneumoniae.

Deborah C Saltman · Miles H Beaman · Steven L Wesselingh

In reply: We thank Saltman for up-to-date information on Wyeth vaccines. Readers will appreciate that our article1 was commissioned in January 2001, and the manuscript delivered in August that year, before the licensing of Meningitec. As the article discussed, group C meningococcus is a minority strain in most regions of Australia. Hence, the vaccine will not prevent most cases of what is already an uncommon disease. Conjugate pneumococcal vaccines should have much wider application in the future, but currently are subsidised for use in only a minority of the at-risk population.

Deborah C Saltman MD, FRACGP, FAFPHM · Miles H Beaman FRACP, FRCPA · Steven L Wesselingh FRACP, PhD

The usual presentation of a returned traveller is with a particular syndrome — fever, respiratory infection, diarrhoea, eosinophilia, or skin or soft tissue infection — or for screening for asymptomatic infection. Fever in a returned traveller requires prompt investigation to prevent deaths from malaria; diagnosis of malaria may require up to three blood films over 36–48 hours. Diarrhoea is the most common health problem in travellers and is caused predominantly by bacteria; persistent diarrhoea is less likely to have an infectious cause, but its prognosis is usually good. While most travel-related infections present within six months of return, some important chronic infections may present months or years later (eg, strongyloidiasis, schistosomiasis). Travellers who have been bitten by an animal require evaluation for rabies prophylaxis.

Series Editors:

Re "MJA Practice Essentials – Infectious diseases 3: Community-acquired pneumonia", by Johnson PDR, Irving LB and Turnidge JD, in the 1 April issue of the Journal (Med J Aust 2002; 176: 341-347). The authors would like to clarify an ambiguity in the text, after discussion with Professor Bart Currie (Director of Clinical Research, Tropical Medicine and International Health Unit, Menzies School of Health Research, Darwin, NT). On page 345, the last paragraph should read: "Tropical Australia: Patients in tropical Australia, particularly those with more severe pneumonia, may be infected with B. pseudomallei (melioidosis) or A. baumannii and thus may require different initial empirical therapy. Patients with CAP in risk classes III or IV who also have risk factors for these infections (eg, diabetes, chronic airways disease, high alcohol intake or renal disease) should receive initial therapy with regimens that include intravenous gentamicin plus ceftriaxone (2 g for adults). All patients in risk class V should receive regimens that include intravenous gentamicin plus meropenem, if available. The regimen needs to be further refined if one of these pathogens is identified.26" In addition, the last footnote to Box 6 on page 345 should be replaced with the following: "¶ In tropical Australia, melioidosis and Acinetobacter baumannii infection should be considered in all patients in risk class V and those with risk factors in risk classes III and IV." Antibiotic recommendations are under constant review because of emerging resistance and changes in epidemiology, and we remind clinicians to refer to the latest updates of Australian antibiotic guidelines when prescribing.

Paul DR Johnson PhD, FRACP · Lou B Irving FRACP, FRACGP · John D Turnidge FRACP, FRCPA

Hendra virus infection should be suspected in someone with close association with horses or bats who presents acutely with pneumonia or encephalitis (potentially after a prolonged incubation period). Australian bat lyssavirus infection should be suspected in a patient with a progressive neurological illness and a history of exposure to a bat. Rabies vaccine and immunoglobulin should be strongly considered after a bite, scratch or mucous membrane exposure to a bat. Japanese encephalitis vaccine should be considered for people intending to reside in or visit endemic areas of southern or eastern Asia for more than 30 days.

Series Editors:

To the Editor: I read with interest the article by Goldsworthy and McFarlane on Howard Florey, Alexander Fleming and penicillin.1 With regard to the cause of Florey's "famous pinched smile", which allegedly hid tooth erosion caused by his drinking dilute hydrochloric acid prescribed for achlorhydria, a more prosaic yet interesting explanation is found in the memoirs of Raymond Valentine Hennessy. Hennessy was Senior Ear, Nose And Throat Surgeon at St Vincent's Hospital, Melbourne, between 1928 and 1951.2 Howard Florey in the late 1930s In August 1936, Florey, who was then Professor of Pathology at Oxford, visited his dying mother in Melbourne. He and his family stayed with his sister, Dr Hilda Gardner. Florey had a supply of sulfanilamide, probably the first in Melbourne, to treat his daughter, who was convalescing from a recent mastoid operation. During his stay, Florey attended a local dentist for treatment of a painful lateral incisor tooth. Some days later (on a Saturday evening), his face had become swollen and he began having rigors. His sister, a medical graduate who was then working as a clinical pathologist and microbiologist at the Melbourne Hospital, appreciated the danger — an abscess of a lateral incisor tooth can produce a cavernous sinus thrombosis — and quickly contacted Raymond Hennessy, who lived nearby. Hennessy had graduated as a dentist before pursuing a career as an ear, nose and throat surgeon and had written about the dangers of a lateral incisor dental abscess.3 After examining Florey, Hennessy told him that the offending tooth required extraction that night. Initially, Florey refused to heed his advice, preferring to see his own dentist the following Monday. Fortunately for Florey, he was persuaded by his sister to have the extraction. Hennessy then telephoned a dentist colleague, and they all met at the latter's surgery in Collins Street, where Hennessy gave Florey a gas–oxygen anaesthetic, and the nervous dentist proceeded to extract the incisor. However, he extracted the normal central incisor, not the offending lateral! On realising his mistake, the dentist "went to water", but Hennessy immediately rose to the occasion and extracted the correct tooth. When Florey woke from the anaesthetic, as Hennessy well remembered, he was not amused. Later, he had a dental plate made but did not like wearing it. Whether he took the sulfanilamide is not known. This episode is not mentioned in Gwyn Macfarlane's biography of Florey.4 However, the photograph of Florey in the frontispiece of this book shows the gap in his upper incisors (pictured). I believe this is the explanation for Florey's "famous pinched smile".

Ivo D Vellar · Thomas B Hugh

To the Editor: The patronising article by Goldsworthy and McFarlane on the discovery of penicillin1 depicts the popular heroic view of Alexander Fleming as a myth, but also promulgates myths of its own. Their description of the Fleming saga is historically accurate. Fleming searched for an answer to the riddle of infection, and, to paraphrase Pasteur, chance in the form of a spore of a rare subtype of Penicillium favoured his prepared mind. Whether or not the spore came through an open window is irrelevant, but the windows in Fleming's laboratory — now preserved as a museum (pictured) — could be opened3 and probably were on occasion, as Fleming was a heavy smoker. Fleming perceived the significance of inhibition (or, more correctly, lysis) of staphylococcal colonies, named the active agent "penicillin" and studied its effect on animals. Goldsworthy and McFarlane are "astonished" that he failed to inject it into infected animals to investigate its therapeutic effect, but the reason is simple: Fleming discovered that penicillin was rapidly inactivated by serum, dashing his hopes for its use as a systemic agent.3 Although he met opposition from his chief, Almroth Wright (known to his students as "Almost Right"), who rejected the view that penicillin might be a useful therapeutic agent, it is absurd to say that Fleming was "a victim of the pessimistic mind-set against toxic chemical antimicrobials". His confidence in its lack of toxicity led him, in 1929, to use penicillin to treat pneumococcal conjunctivitis in one of his assistants, with dramatic success.2 Site of Fleming's laboratory The Clarence Wing, St Mary's Hospital, London, in 1910. Fleming's laboratory, where penicillin was discovered in 1928, was on the third floor of the tower on the right. The windows of the laboratory could be opened by an internal system of ropes and pulleys, but a more likely source of the Penicillium spore was a dumb-waiter shaft communicating with a mycology laboratory on the floor below.2 To say that "Fleming had little idea what to do with his mould apart from dabbing it on infected wounds" unfairly trivialises his actions after the discovery. In addition to clinical and animal studies, he had the mould identified, deposited a culture with the collection held by the Medical Research Council and published his observations. He set two researchers to work purifying the active principle of the mould broth, and established that penicillin was soluble in alcohol and that its stability was pH-dependent. He also developed an assay for penicillin and defined the range of organisms that were sensitive to it. He sent cultures of the penicillin-producing strain to many laboratories, including Oxford, where that very culture later provided the starting point for Chain and Florey's work. Fleming's subsequent work on penicillin was stalled by his lack of biochemical expertise; he was unable to overcome the difficulties of purification and stabilisation.2 Fleming is recorded as saying, "It's up to the chemists now, I'm no chemist".2 It is quite untrue that "he then effectively forgot about it for 13 years". Although Fleming ceased clinical work on penicillin in 1934, he continued with laboratory studies. A contemporary at St Mary's Hospital, Dr A G Cross, recalled that in the 1930s "penicillin was on his mind all the time and in the minds of those who worked with him".2 Fleming had his faults, but the genius of his prepared mind did indeed present humanity with a fairy tale come true. Perhaps Ernst Chain, who did not particularly like Fleming, should have the last word: "There is no doubt that this discovery, which changed the history of medicine, has justly earned [Fleming] a position of immortality."2

Ivo D Vellar · Thomas B Hugh · Peter D Goldsworthy MB BS · Alexander C McFarlane MD, Dip Psychother, FRANZCP

In reply: Our article aimed to show how history is often rewritten in narrative forms that are more appealing to the human need for heroes and for clear, memorable moral lessons.1 The challenge is to sort out whether the matters at stake are those of narrative style or substantial differences of fact. Hugh felt our approach was patronising to Fleming — but we were at pains to emphasise his "genius" for making important causal connections. He also had a genius for seeking adulation — which in no way disqualifies him from deserving to share the Nobel Prize for Medicine with Chain and Florey. Hugh also criticised our assertion that "Fleming had little idea what to do with his mould apart from dabbing it on infected wounds" — yet his counterexample, that in 1929 Fleming used "penicillin to treat pneumococcal conjunctivitis in one of his assistants", illustrates the point. Let us also not forget that a Belgian group had discovered the penicillin mould in 1920, and recognised its antimicrobial properties well before Fleming did. The challenge is to foresee and drive the application of knowledge rather than to leave facts in a dormant but pregnant state. Vellar's fascinating letter proposes that a dental abscess and two extractions, rather than Florey's drinking of hydrochloric acid, caused his "pinched smile". A mutually compatible hypothesis is that Florey was prone to this infection because of tooth damage caused by the acid. Vellar also provides further support for the quixotic spread of knowledge and the personal motivations and obsessions that influence researchers. Florey's transport of sulfanilamide to Melbourne was apparently not to popularise the new and revolutionary drug, but to treat his daughter. It also raises a fascinating, if ironic, possibility: was Florey's life saved by sulfanilamide, allowing him to continue on his yet-to-be-forged endeavour of the purification of penicillin?

Ivo D Vellar

To the Editor: Community-acquired methicillin resistance in Staphylococcus aureus was only reported in eastern Australia as recently as 1998.1 We report a case of community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) causing cellulitis and bacteraemia. A 30-year-old man presented to the emergency department with a short history of heel pain. There was no history of trauma, diabetes, drug misuse, contact with hospitals or previous antibiotic treatments before the current illness. Examination showed that he had a temperature of 37.7°C and sinus tachycardia of 120 beats per minute. There was extensive cellulitis surrounding a superficial collection of pus over the left heel; this was incised and drained. Initial investigations showed only neutrophilia. Blood cultures, but no swabs, were taken. Therapy with daily intravenous injections of 1 g ceftriaxone, given at home by an ambulatory care service, was initiated. The following day, blood cultures showed the presence of gram-positive cocci identified as a Staphylococcus sp., and the treatment was changed to 2 g of cephazolin 12-hourly, intravenously. On the second day Staphylococcus aureus resistant to oxacillin was isolated. There was susceptibility to erythromycin, clindamycin, tetracycline, ciprofloxacin, vancomycin, rifampicin and fusidic acid. Treatment with vancomycin (1 g 12-hourly, by means of a peripherally inserted central catheter) resulted in clinical improvement within 48 hours and was continued for a total of two weeks, followed by oral rifampicin and fusidic acid. A bone scan and echocardiogram showed no significant abnormality. Resolution was complete at six weeks and the patient returned to work. Methicillin-resistant Staphylococcus aureus (MRSA) is now a common cause of skin and soft tissue infections.2-4 MRSA was not acquired outside hospital until the 1980s, when intravenous drug users from Detroit were reported with MRSA bacteraemia. Such community-acquired strains have now been reported worldwide, including in Australia.5 These strains are usually non-multiresistant MRSA,3 which are highly pyogenic, readily communicable and predominantly cause skin and soft tissue infections. However, CAMRSA endocarditis and a bacteraemic osteomyelitis have been described. We believe this to be the first case of CAMRSA bacteraemia to be reported in Australia. Community-acquired MRSA strains have become a common cause of community-acquired staphylococcal infection in Australia.2,3 It is now recommended that swabs be routinely taken to cover the possibility of drug-resistant organisms such as MRSA.1-3 The appropriate initial management of suspected or high-risk cases is unclear, but might include treatment with vancomycin or gentamicin before the availability of antibiotic sensitivity test results.

Nicholas Collins · lain B Gosbell · Stephen F Wilson

Although most naturally occurring infections with anthrax and plague are cutaneous, both organisms are most likely to be deliberately disseminated in aerosolised form, resulting in severe pulmonary illness. Mortality from both would be high and rapid in the absence of early and effective treatment, making swift and effective liaison between alert clinicians and public health authorities crucial to an effective response. Differentiating features include mediastinal widening (anthrax) and haemoptysis (plague). Doxycycline and ciprofloxacin are effective agents for prophylaxis and treatment for both diseases. Medical advocacy for strengthening the Biological Weapons Convention, particularly with an enforceable protocol including verification and compliance provisions, is needed.

Michael Whitby FRACP, FRCPA · Tilman A Ruff MB BS(Hons), FRACP · Alan C Street MB BS, FRACP · Frank Fenner MD, FRS

Soft tissue infections are common and usually respond rapidly to oral antibiotics; if empirical therapy fails then exposure to unusual organisms should be considered. Septic arthritis requires early recognition, identification of the infecting pathogen and urgent joint washout to prevent irreversible cartilage and bone destruction. Prosthetic joint infection is uncommon but has high morbidity; the best outcomes are achieved with removal of the prosthesis and replacement after at least six weeks of antibiotic therapy. Osteomyelitis often complicates diabetic foot infection with ulceration and is rarely cured by antibiotics alone; early surgical intervention achieves the best outcome.

Series Editors:

Commercially available nucleic acid amplification assays (eg, polymerase or ligase chain reaction) are now the "gold standard" tests for genital chlamydial infection and also have a role in screening for gonococcal infection. Single-dose oral antibiotics are available for treatment of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infections. Strains of N. gonorrhoeae in urban Australia are often penicillin resistant, while strains from South East Asia and those in homosexually active men may show high-level resistance to quinolones. Imiquimod, a novel immune-response modifier, is now available for effective, safe, self-administered treatment of genital warts. The Pap smear remains the cornerstone of screening for precursor lesions of cervical cancer, but human papillomavirus genotyping may have a role in clinical decision-making for women with equivocal or early precancerous lesions. Treatment of primary genital herpes changes the clinical course, and long-term suppressive therapy is effective for those with multiple recurrences.

Francis J Bowden FRACP, MD · Sepehr N Tabrizi PhD · Suzanne M Garland MD, FRCPA · Christopher K Fairley FRACP, PhD

A more coordinated, national approach to parasite control would have substantial benefits In January 2000 the World Health Organization launched a program aimed at global elimination by 2020 of the lymphatic filarial parasites Wuchereria bancrofti and Brugia malayi. These parasites together infect in excess of 120 million people, and cause significant morbidity through elephantiasis. A major stimulus to the implementation of this and other programs, such as those aimed at the elimination of leprosy and Chagas' disease, was the successful global elimination of smallpox in 1977, and major advances in programs to control polio, measles, dracunculiasis (guinea worm) and onchocerciasis (river blindness). So, what of Australian parasite control programs? In Australia, endemic malaria and lymphatic filariasis have been eradicated, and leprosy, a once feared and politically significant disease, is in decline through sustained control programs conducted by dedicated public health agencies over long periods using effective drugs. However, the same cannot be said for other common parasitic diseases which are still endemic in Australia, including scabies, giardiasis, cryptosporidiosis, hookworm, strongyloidiasis and trichuriasis. These parasite infections have remained highly prevalent among Indigenous Australians living in the tropical north of the country in areas where infrastructure development has lagged, and improvements in living standards have not matched those seen elsewhere.1-3 Rather than being of trivial importance, such parasite infections cause substantial preventable morbidity. Secondary infection of scabies lesions with group A streptococci contributes to the exceptionally high rates of rheumatic fever and renal disease seen in Indigenous people, while enteric parasites cause a range of adverse health effects, including anaemia from hookworm, septicaemia from strongyloidiasis, and malabsorption and diarrhoea in children from giardiasis and cryptosporidiosis. Further, the merit of control programs for geohelminth infection is supported by studies suggesting benefits in educational outcomes among children treated for these infections.4 Despite the progress made in hookworm control during the course of the Australian Hookworm Control Program in the early part of last century, this infection has remained endemic in many Indigenous communities across our tropical north, and contributes to iron deficiency and anaemia in women and children. The limited success of attempts to control hookworm in one remote northern Australian Indigenous community of about 350 people has been published in the Journal (with rates of hookworm infection documented in 1992 of up to 93% in children 5–14 years of age).2 Recently, our group has published the successful outcome of a 78-month hookworm infection control program in the same community.5,6 This program's success was due to close liaison with the community, the setting of clear goals, and a commitment to improve environmental infrastructure and local health education, as well as regular targeted, population-based chemotherapy over a sustained period. The change of anthelmintic from pyrantel (to which parasite resistance had been demonstrated7) to single-dose albendazole was an additional significant factor in the success of the program. Parasite control programs based on community-wide distribution of albendazole among school-age children have also been implemented in the Northern Territory, and a similar community treatment strategy using permethrin therapy for scabies has recently been shown to reduce the prevalence of scabies in one community from 35% to 3%.3 Such successful programs are useful models for further community programs and national initiatives. Could and should parasitic disease in northern Australia be controlled more effectively? While the determinants of parasitic disease in northern Indigenous communities are complex, there are common themes. Contributing factors include poverty, lack of health knowledge, poor environmental infrastructure and housing, remoteness from health services, family mobility across health regions, and haphazard opportunistic treatment of parasites as they are encountered in clinical practice. To be successful, parasite control programs must be consistent, coordinated and sustained, and accompanied by local health education and improvements in health infrastructure. At present, regional and State parasite control programs lack a consistent approach across primary and secondary sectors and across State borders, and in some regions are ignored or left largely to enthusiasts. A more coordinated, national approach to parasite control would have substantial benefits: It would allow Aboriginal health organisations to fully participate and "own" the program from the national planning level through to the local community, thus facilitating rational debate on this emotive issue; Funding would be made available for nationally agreed strategies and continuing infrastructure improvements in affected communities; The use of standard surveillance techniques, reporting and targets would enable monitoring of progress; The reduction of parasite burden would be achieved through coordinated, programmed use of proven, safe drugs, including albendazole, ivermectin, tinidazole, and permethrin, at a community level; and Programs would be monitored for the development of drug resistance (a problem already present in veterinary practice where related drugs are used8). Two critical factors for the success of such a program are political will, and a will on the part of the communities themselves, together with local healthcare providers, and government and Indigenous health organisations. While the cost of the drugs is not the major barrier to the implementation of such programs, the positive publicity gained by two pharmaceutical companies from their leadership in donating ivermectin and albendazole to the WHO-sponsored filariasis program could have some local lessons. Leadership in Australian parasite elimination programs should come from both the Indigenous and medical communities through an alliance of Indigenous people and public health, infectious diseases and paediatric practitioners.

James S McCarthy · Stuart C Garrow

To the Editor: The Australian Defence Force (ADF) has sustained many cases of malaria following service in East Timor.1 To reliably prevent relapse of malaria caused by the Chesson strain of Plasmodium vivax present in this region, larger doses of primaquine are required2 (up to 6 mg/kg total dose,3 compared with > 3.5 mg/kg to prevent relapse of sub-Saharan vivax malaria4). The ADF uses 1500 mg chloroquine (total base) followed by 315 mg primaquine (total base) for the treatment of vivax malaria, which, in Australia, is commonly treated either without primaquine or with inadequate dosages of either chloroquine or primaquine.5 A fit, 65 kg male soldier who deployed to East Timor from October 1999 to May 2000 experienced one episode of vivax malaria during his deployment and a further four episodes on return to Australia (Box). Having had malaria in East Timor, he complied closely with postexposure prophylaxis with primaquine and tolerated his dose (7.5 mg three times daily with meals) well for the required 14 days (315 mg total). He was seronegative for HIV, hepatitis C, and dengue IgG and IgM, and was not glucose-6-phosphate dehydrogenase deficient. The Table shows that our patient had a parasite that was apparently responsive to chloroquine, although it did not respond as readily in the last episode. In his first episodes of malaria on return from East Timor, he received the recommended dose of primaquine, but developed recurrences in the absence of further exposure to malaria. These relapses presumably indicate an inadequate response to the primaquine. The total dose of primaquine used for postexposure prophylaxis and treatment of the first episodes in Australia was about 4.8 mg/kg. He has subsequently received a treatment of 6 mg/kg total primaquine (see Table, Episode 5). This follows extended suppression with chloroquine before and doxycycline during a three-month deployment to Malaysia. There has been no further relapse six months after treatment. Chesson-strain vivax malaria is known to be difficult to treat and in which to prevent further relapse. Adequate primaquine to treat vivax malaria from other areas is not adequate for that contracted to the immediate north of Australia. Relapsing vivax malaria from East Timor may require a dose of 6 mg/kg of primaquine to prevent further relapse. Parasite density and treatment during the patient's episodes of malaria Episode Date of diagnosis Parasite density Treatment 1 1 April 2000 Positive on immunochromatographic test* Chloroquine 1500 mg, continued doxycycline 100 mg daily, primaquine 315 mg from 2 May 2 17 July 2000 23 000/µL Chloroquine 1500 mg, then primaquine 315 mg 20 July 2000 No parasites seen 3 26 Sep. 2000 8607/µL Chloroquine 1500 mg, then primaquine 315 mg 29 Sep. 2000 No parasites seen 4 11 Dec. 2000 11 400/µL Chloroquine 1500 mg, then weekly for two months† 14 Dec. 2000 No parasites seen 5 3 April 2001 Occasional trophozoites on thick and thin film Chloroquine 1500 mg, then weekly for one month; doxycycline for three months, then primaquine 420 mg 6 April 2001 Occasional trophozoites only on thick film * Immunochromatographic test used in the field. † Patient ceased treatment.

Scott J Kitchener · Isaac Seidl

The use of biological agents as weapons of war is not new. In the 14th-century siege of Kaffa, on the Black Sea, the attacking Tartars catapulted bodies of plague victims at the defending Genoese, who contracted the disease and abandoned the city. Over the past century, many countries have developed the capacity to use biological agents to produce casualties in humans and domestic animals and to damage crops and environmental systems. Some biowarfare programs are known to have continued despite the adoption by 144 countries of the 1972 Biological Weapons Convention, which prohibited development or acquisition of such weapons. Early recognition of unusual clinical illness by physicians is an integral part of the public health response to a biological attack. We review the features of four biological agents of greatest concern. In this article, we discuss smallpox, a disease not seen in the world for the past two decades, and botulism. A subsequent article will discuss anthrax and plague. SmallpoxEpidemiologyIn a world declared free of smallpox in May 1980,1 this disease has characteristics that make it particularly suitable for biological warfare. It can be spread person-to-person. With the cessation of vaccination programs over 20 years ago, immunity has waned among those who have been vaccinated, while those born since 1980 are unvaccinated. The virus spreads by the respiratory route (primarily by droplet nuclei or aerosols expelled from the nasopharynx of infected people) or by direct contact (being released from ulcers on the oral mucosa from the time lesions appear on the skin and two to three days after onset of fever). It has also been transmitted by soiled clothing and blankets used by patients. Smallpox spreads rapidly between close family contacts2 and within hospitals when no special precautions are taken.3 Smallpox as a weaponOther features of smallpox that contribute to its suitability as a weapon are the stability of the virus in aerosol form and the likely small infective dose.4 Smallpox virus was added to the biowarfare program of the Soviet Union in 1980. Successful methods of stockpiling large amounts of this virus and delivering it from aircraft or ballistic missiles have been developed.5 With the discontinuation of the Soviet civilian biowarfare program in 1992, hundreds of experienced scientists became available to sell their services and take smallpox virus to other countries.5 The Indian strain of smallpox virus, used in the Soviet biowarfare program, causes a mortality of about 30% in unvaccinated people. Clinical features and diagnosisThe incubation period of 10–14 days ends with sudden onset of fever, headache and backache, usually severe enough to confine the patient to bed. Fever usually continues as the rash develops, with pain associated with pustule growth. Scabs develop and gradually separate, leaving pitted scars. The rash is the most important feature allowing early recognition of smallpox (Box 1). Most cases have been "ordinary type" smallpox, which has pustular lesions, but variant forms ("flat" and "haemorrhagic type" smallpox) occurred rarely and were almost always fatal. Modified smallpox occurred in people with waning immunity after vaccination and those who were vaccinated very early in the incubation period, and comprised a few skin lesions, which evolved more rapidly than those in unvaccinated people. Clinical diagnosis can be confirmed by electron microscopy of vesicular or pustular fluid or scabs, which should be collected and processed under maximum containment conditions. Management and preventionThe only proven effective treatment for smallpox is vaccination before or within three days of exposure, which may abort or modify the severity of an attack. Other treatment is supportive only, plus antibiotic therapy if secondary bacterial infection develops. Strict quarantine with respiratory isolation for 17 days is required of all cases and direct contacts of index cases. Vaccination with vaccinia virus is effective in preventing smallpox for at least five years and may prevent or modify infection for a much longer period, but this varies greatly from person to person. However, very few doses of vaccine are available worldwide at present. Furthermore, smallpox vaccination is associated with more severe adverse effects than any other type of vaccination: for example, encephalitis occurs at a rate of one per 300 000 primary vaccine doses and a quarter of cases are fatal, with some survivors having permanent neurological deficits.4 Therefore, both the World Health Organization and the United States Centers for Disease Control and Prevention have recommended that it should be used only to contain suspected cases and not for mass vaccination.6 BotulismEpidemiologyBotulism is extremely rare in Australia, with no reported foodborne cases since 1991.7 The causative organism, Clostridium botulinum, is an anaerobic, spore-forming, gram-positive rod found in soil (Box 2). It produces a potent neurotoxin that causes paralysis of skeletal and smooth muscle by interfering with acetylcholine release at the neuromuscular junction. Botulism as a weaponBotulinum toxin was first developed as a biological weapon over 60 years ago; it can be aerosolised, or used to contaminate food,8 and the estimated lethal oral dose is 70 µg. The Aum Shinrikyo cult released aerosolised toxin in Japan in the 1990s, but fortunately no cases of botulism resulted. The Soviet Union and Iraq have produced large amounts of botulinum toxin, and Iraq loaded toxin into missiles and bombs.8 Clinical featuresTwo forms of botulism could arise from deliberate release of botulinum toxin — foodborne and inhalational botulism. In contrast, gastrointestinal (infant) and wound botulism arise from infection with C. botulinum, rather than ingestion or inhalation of toxin, and are unlikely to occur in a biological attack. Foodborne botulism, the most common natural form of the disease, results from ingestion of preformed toxin that is produced when food contaminated with C. botulinum has been stored under anaerobic conditions. Cases are mostly associated with improperly home-bottled or preserved foods, but could potentially result from intentional addition of toxin to food. Botulism after inhalation of aerosolised toxin is an unnatural, man-made form of the disease, and would be the intended result of toxin delivery by missiles, bombs or aerosolisation devices. Only one instance of inhalational botulism has been reported, involving accidental exposure of three veterinary personnel to toxin re-aerosolised from animal fur.8 The incubation period for gastrointestinal botulism and probably also inhalational botulism (based on animal studies) is usually 12 to 72 hours. All forms of botulism have identical clinical features, with the exception that foodborne botulism may be preceded by gastrointestinal symptoms (nausea, vomiting, diarrhoea, abdominal cramps).8 The pattern of illness is characteristic: onset with cranial nerve palsies of bulbar distribution, followed by descending motor weakness (from head and chest muscles to upper, then lower, limbs) in a patient with a normal conscious state and no fever.9 Absence of sensory changes is another important negative feature. Reflexes are preserved early, but may be lost with time. Dilated pupils, blurred vision, dry mouth and constipation indicate parasympathetic involvement. Severity of the weakness and its rate of progression vary, depending on the amount of toxin ingested. With modern medical therapy, mortality of foodborne botulism is less than 10%. DiagnosisDiagnosis is initially clinical. The principal differential diagnoses are the Miller–Fisher variant of Guillain–Barré syndrome (a demyelinating condition causing cranial nerve palsies and absent deep tendon reflexes) and disorders of the neuromuscular junction, such as myasthenia gravis. These and other conditions can be differentiated from botulism on the basis of clinical signs (eg, impaired consciousness in brainstem stroke or infection), analysis of the cerebrospinal fluid (infection and Guillain–Barré syndrome), neuroimaging (stroke) and electromyography (myasthenia gravis). Laboratory testing for botulism is complicated and time consuming and is available only through selected public health laboratories. To detect toxin, mice are inoculated with serum, faeces or vomitus; the organism, if present, can also be cultured from these specimens. Results are not available soon enough to assist initial diagnosis or management. Management and preventionPrompt administration of botulinum antitoxin, available in the US but not Australia, lessens disease severity. As the toxin is an equine preparation, serum-sickness-like reactions may occur in some recipients, but anaphylaxis is rare. Otherwise, treatment is supportive. Close respiratory monitoring is essential, and patients should be admitted to an intensive care or high-dependency unit. In one foodborne outbreak, 20% of patients required mechanical ventilation. An investigational toxoid vaccine has been given to laboratory and military personnel in the United States but is not available for more widespread use. 1: Smallpox lesions in an unvaccinated child Evolution of smallpox lesions from papules (top left; three days after onset of fever) to vesicles and pustules (bottom right; nine days after onset of fever). For the first two to three days, the rash of smallpox resembles that of chickenpox, but the two can be differentiated by the following: Smallpox lesions appear after two to three days of prominent prodromal symptoms (fever, headache and backache) and develop slowly (over nine to 10 days). Chickenpox lesions develop rapidly after a one- to two-day prodrome (fever and malaise). All smallpox lesions develop at the same pace and, on any part of the body, appear identical. Chickenpox lesions are much more superficial and develop in crops over a two- to four-day period, with scabs, vesicles and pustules seen simultaneously on adjacent areas of skin. Smallpox lesions are most concentrated on the face, arms and legs, and may occur on the palms or soles. Chickenpox lesions are most dense over the trunk and almost never found on the palms or soles. 2: Clostridium botulinum Gram-positive rods with characteristic subterminal spores (Gram stain; original magnification x 1000). (Picture courtesy Microbiological Diagnostic Unit, Public Health Laboratory, University of Melbourne, VIC.)

Michael Whitby FRACP, FRCPA · Alan C Street FRACP · Tilman A Ruff FRACP · Frank Fenner MD, FRS

A growing range of infections can be safely and effectively treated with parenteral antimicrobial therapy at home, including cellulitis, pyelonephritis, pneumonia, endocarditis, osteomyelitis, septic arthritis and deep abscesses. Patients may be admitted to HITH directly from the emergency department or after a period of in-hospital care; they must be thoroughly assessed for suitability, including clinical stability and social circumstances, and both patient and carer consent must be obtained. Patients should be medically reviewed weekly at the hospital to monitor progress of therapy and check for possible complications, including adverse drug reactions. Antibiotic selection should be based on appropriate prescribing principles rather than purely dosing convenience. Innovative dosing regimens, including once-daily aminoglycosides, continuous-infusion β-lactams (eg, flucloxacillin), once- or twice-daily cephalosporins (eg, cephazolin) and oral fluoroquinolones (eg, ciprofloxacin) provide effective therapy for a wide range of infections that would have previously required in-hospital care. Appropriate use of HITH leads to improved patient and carer satisfaction, efficient in-hospital bed use and possibly some financial efficiencies.

Series Editors:

To the Editor: Donovan and colleagues bring attention to the restrictions placed by the Health Insurance Commission via the Medicare system on clinicians investigating patients for sexually transmitted infections (STIs).1 In their study of Sydney general practitioners, they suggested that reform was required to the three-test pathology testing rule to improve gonorrhoea screening in high-risk individuals living in a region of epidemic gonorrhoea. In the Kimberley region of Western Australia, where we practise, syphilis, gonorrhoea and chlamydia continue to be endemic. Best-practice guidelines for primary healthcare providers in WA state that investigation for other possible STIs is essential to the care of patients with STIs or HIV infection.2 Health policy should be based on best-practice standards. For patients with confirmed or suspected STIs, this means that Medicare funding should meet the full costs of all tests for suspected STIs (as indicated by clinical need and best-practice guidelines) to enable and facilitate effective control of these infections at the population health level. An Australian legal precedent exists for medical practitioners regarding testing for STIs. In the New South Wales Supreme Court case of BT v Oei, it was found that a doctor has a duty of care to offer testing for other STIs to a patient with one STI or a suspected STI.3 In that case, a sexual partner of an HIV-positive patient brought successful legal action against her partner's doctor for failing to diagnose HIV infection in her partner. The doctor was found negligent in failing to offer an HIV test to a patient with ongoing symptoms who had been found to be infected with hepatitis B virus and whose only risk factor for this infection was unprotected sex. The doctor's duty of care was found to extend to the patient's sexual partner, who became infected with HIV after unprotected sex with her partner. Given that best-practice guidelines and a legal precedent exist which confirm that a medical practitioner should offer testing for other STIs to a patient with one STI or a suspected STI, what are the medicolegal implications of the Health Insurance Commission's three-test rule? Comment: The Journal sought a comment from the Commonwealth Department of Health and Ageing, but after three months had yet to receive a response.

Graeme H Johnson MB BS (Hons), BMedSci(Hons) · Donna B Mak FAFPHM, FACRRM