Infectious diseases

In reply: As we mentioned in our article, erythromycin is the drug of choice for treatment and prophylaxis of pertussis in people of all ages.1 Several statements can be made about the use of macrolides in this condition.2 Firstly, erythromycin has been shown to decrease the duration of illness when given early in pertussis infection and to eliminate Bordetella pertussis from the nasopharynx. Secondly, erythromycin therapy for index cases has been shown to reduce the rate of secondary cases of pertussis in households in uncontrolled studies.3 However, in a recent randomised placebo-controlled study, while erythromycin reduced the incidence of culture-positive pertussis in household contacts there was no reduction in respiratory symptoms.4 Thirdly, clarithromycin and azithromycin have been shown to be at least as effective as erythromycin in treating pertussis in two small comparative studies.5 As Massie et al point out, there are no clinical studies of the use of roxithromycin in this condition, and laboratory in-vitro sensitivity studies suggest roxithromycin may be inferior to erythromycin. Roxithromycin is the most widely used macrolide in Australia, but it requires a leap of faith and extrapolation to prescribe this drug for prophylaxis or treatment of pertussis. In the one case in our series where roxithromycin was prescribed, this was not our decision. We would have recommended erythromycin on the basis of the available clinical evidence. Vaccination is preferable to antibiotic prophylaxis for long-term control of pertussis.

Joseph G McCormack · Natalie M Spearing · Robert L Horvath

Meningococcal septicaemia has high mortality, especially when the diagnosis is delayed or missed. Early recognition is not always straightforward, as classic clinical features may be absent or overlooked at initial presentation. Septicaemia without focal infection accounts for 15%–20% of cases of meningococcal disease and is the most worrisome manifestation in terms of diagnosis and outcome; in contrast, meningococcal meningitis is usually straightforward to diagnose, with a relatively good prognosis. Useful early clinical clues to meningococcaemia include: – a haemorrhagic (petechial or purpuric) rash; – blanching macular or maculopapular rash that appears in first 24 hours of illness; – true rigors; – severe pain in extremities, neck or back; vomiting, especially in association with headache or abdominal pain; rapid evolution of the illness; – concern of parents, relatives or friends; – patient age (highest incidence at age 3–12 months, followed by 1–4 and then 15–19 years); and – contact with a patient with meningococcal disease. In addition to specific clues, clinicians should look at the whole pattern of the illness. Timely clinical review is essential if there is doubt about the diagnosis. In any acutely febrile patient, it is prudent to ask "Why is this patient seeking help now?", then "Could this patient have meningococcaemia?".

Allen P Yung FRACP · Malcolm I McDonald FRACP, FRCPA

To the Editor: I was pleased to read the article on Ross River virus (RRV) disease by Mylonas and colleagues,1 because it included information on the cost of the disease. This makes it much easier to do something practical from a government and health economics perspective about the problem of RRV. The cost of $1018 per patient, including costs of negative tests looking for cases, sums to a total estimated cost to the nation of $5 million per annum (based on the reported average of 5000 cases per year in the study by Harley and colleagues2). Of note, $567 was spent per patient on diagnostic tests (56% of the total cost per patient), while the authors noted that in many cases the condition was self-limiting. I begin to wonder what is the use of spending $567 per patient diagnosed to prove a largely self-limiting condition that is treated symptomatically? Banning RRV testing could save $2.8 million per annum, which would be immediately available for mosquito control measures, and perhaps vaccine research, to reduce the burden of RRV disease. We could model the impact of a vaccination program — vaccine development cost, vaccine unit production cost, vaccine delivery, population target, and savings in disease prevented — to determine whether funding of vaccine research is worthwhile. The point is that without economic data we cannot make sensible "evidence-based" clinical management decisions. We are trapped in a scientific paradigm, and the health system implements unpopular cost–control interventions because it needs to control spiralling costs. We clinicians need to do better. If other researchers would follow the lead of Mylonas and colleagues and explore the economics of their subject, we would be able to make more rational choices about healthcare. It is up to clinicians to understand the economic agenda and suggest interventions that make both economic and clinical sense. We can then begin to make more efficient and rational use of our health dollars, relieving stress on a stressed system.

Ian R Cheong

To the Editor: Dugdale proposed recently in the Journal that people who have a skin reaction to mosquito bites are less likely to be infected by Ross River virus than those who do not.1 As he quotes Kumar, who made a similar comment about malaria infection,2 one could presumably extend his idea to other conditions transmitted by mosquitoes. This accords with my own personal experience of dengue fever acquired in Fiji. While serving there, I had two separate proven infections with dengue virus. As I react very little to mosquito bites, I could not identify the time of infection. Indeed, on the first occasion, I had just returned from a three-month stay in Adelaide and could not recall being bitten by a mosquito at all. In contrast, my wife, who developed large weals whenever bitten, went through at least three epidemics of dengue without being infected. My advice to travellers who consult me is that there is an advantage to reacting badly to mosquitoes, as one is then more likely to take anti-mosquito precautions, whereas the non-reactor is more likely to disregard them. However, Dugdale's suggestion that a local inflammatory reaction may be a factor in defence against infection is intriguing and worth following up. It should be simple to enquire retrospectively about reactions to mosquito bites in those who have had a mosquito-borne disease, as Dugdale has done for Ross River virus infection. This would provide evidence on which to base pathological and immunological studies.

Michael Sorokin

To the Editor: Dugdale recently suggested that people who develop skin reactions to mosquito bites may be protected against Ross River virus (RRV) disease.1 He noted that seven patients with a history of RRV disease all reported no skin reaction to mosquito bites, and 18 patients with no past history of RRV disease reported reacting to such bites. We argue that this correlation is entirely to be expected, as the lack of reaction to mosquito bites illustrates that the individuals have been previously exposed to many bites. At least two studies have shown a clear inverse correlation between mosquito exposure and bite reactions.2,3 Clearly, exposure to a large number of mosquito bites increases the risk of infection.4 Thus, a reaction to mosquito bites probably does not protect against RRV disease, but is simply a marker for low exposure to mosquito bites and therefore low risk of RRV infection. The rationale behind the association of itching bites and protection against RRV infection is also tenuous. Virus is likely to reach the circulation within seconds of introduction by the mosquito, whereas allergic reactions take minutes to develop. It is unlikely that a local reaction will affect viral replication at distant sites. In Dugdale's study, only people with a history of symptomatic RRV disease had undergone RRV serological testing. As about 30% of Queenslanders are seropositive,5 and 60%–75% of RRV infections are thought to be asymptomatic,6 some of the 18 people with no past history of RRV disease might be expected to have had asymptomatic RRV infection. This raises the question, does reaction to mosquito bites correlate with asymptomatic RRV infection?

Peter A Ryan · Jillann F Farmer · Brian H Kay · Andreas Suhrbier

Re the article "Water and the environment: a natural resource or a limited luxury?", by Karin Leder, Martha I Sinclair and John J McNeil in the 2/16 December issue of the Journal (Med J Aust 2002; 177: 609-613). Due to a software error, the affiliation of the authors was incorrectly given as the National Centre for Epidemiology and Population Health, Australian National University, Acton, ACT. The correct affiliation and contact details are: Department of Epidemiology and Preventive Medicine, Monash University – Central and Eastern Clinical School, Alfred Hospital, Melbourne, VIC. Karin Leder, FRACP, MPH, DTHM, Head of Infectious Disease Epidemiology; Martha I Sinclair, PhD, Senior Research Fellow; John J McNeil, FRACP, PHD, FAFPHM, Head of Department. Correspondence: Dr Karin Leder, Department of Epidemiology and Preventive Medicine, Monash University – Central and Eastern Clinical School, Alfred Hospital, Commercial Road, Melbourne, VIC 3004. karin.lederATmed.monash.edu.au The html and pdf versions of the article available on this website have been corrected.

Karin Leder FRACP, MPH, DTHM · Martha I Sinclair PhD · John J McNeil FRACP, PHD, FAFPHM

Objective: To investigate possible routes for human infection by the dog hookworm (Ancylostoma caninum).Design, setting and participant: Relatively small numbers of infective larvae were administered orally and percutaneously to an informed healthy volunteer (J K L) under medical supervision, at intervals between May 1998 and May 1999.Main outcome measures: Symptoms; weekly blood eosinophil counts; faecal microscopy.Results: A marked blood eosinophilia followed a single oral exposure to 100 infective larvae, while faecal examination remained negative. Eosinophil counts then declined gradually, although a rapid, spontaneous rise several months later, at the beginning of spring, possibly indicated reactivation of dormant larvae. Blood eosinophil numbers did not rise significantly after percutaneous infection with 200 larvae. A subsequent, smaller, oral inoculum of 20 larvae provoked an eosinophil response similar to that of the first experiment.Conclusions: Our findings suggest that, following ingestion, some infective larvae of A. caninum develop directly into adult worms in the human gut (as they do in dogs). While the percutaneous route might be the most common means of human exposure to canine hookworm larvae, leading generally to subclinical infection, oral infection may be more likely to provoke symptomatic eosinophilic enteritis.

Juergen K Landmann BSc(Hons) · Paul Prociv MB BS, PhD, FRACP, FRCPA

Chronic HBV infection is common in remote Aboriginal and Torres Strait Islander communities, where resources are scarce and patients may have several concurrent illnesses. The management of chronic HBV infection has changed over recent years, with greater application of serological and radiological investigations and new, more acceptable treatments for chronic liver disease, cirrhosis and hepatocellular carcinoma. Optimal follow-up procedures for patients with chronic HBV infection are still being debated, but may not be applicable to Aboriginal and Torres Strait Islander communities where factors such as endemicity, remoteness, frequent comorbidities, shorter life expectancy and cultural differences in health priorities must be taken into consideration. We have defined an algorithm to assist primary care providers caring for patients with chronic HBV infection in Aboriginal and Torres Strait Islander communities. Patients are divided into one of three categories for follow-up and referral based on clinical features, and results of liver enzyme and serological tests.

Dale A Fisher FRACP · Sarah E Huffam FRACP

A 55-year-old taxi driver presented with a three-week history of intermittent sore throat associated with fever and rigors, which responded to paracetamol. On the morning of admission, he woke with severe aching pain in the left groin radiating to the scrotum, with associated vomiting, fever and rigors. There were no urinary symptoms and he had not had any recent new sexual contacts. His medical history included uncomplicated haemochromatosis only. Examination revealed a temperature of 39.6°C and sinus tachycardia. Otorhinopharyngeal, parotid and abdominal examinations were normal. Scrotal examination revealed a 4 cm, hot, swollen, erythematous area, with tenderness in the left epididymis and left testis. The results of investigations, including streptococcal serology (confirming recent infection) and ultrasound imaging, are shown in Box 1 and Box 2. Urine microscopy and culture were negative. Streptococcus pyogenes susceptible to penicillin was isolated from both aerobic and anaerobic blood culture bottles at 24 hours. Polymerase chain reaction tests of urine were negative for Neisseria gonorrhoeae and Chlamydia trachomatis. Despite commencement of intravenous penicillin, the patient required incision and drainage of the scrotum on Day 4. He was discharged from hospital nine days after presentation on a two-week course of oral amoxycillin and made a full recovery. DiscussionEpididymo-orchitis can result from bacterial or viral infections. Predisposing trauma may be identified, but the majority of cases appear to be idiopathic. Different types of causative bacteria occur more frequently in certain age groups: 1,2 for example, urinary tract pathogens (eg, Escherichia coli, Proteus mirabilis, Enterobacter spp.) in men over 35 years; sexually acquired pathogens (eg, N. gonorrhoeae, C. trachomatis) in sexually active men under 35 years; and pathogens acquired as part of a systemic infection (eg, Haemophilus influenzae, N. meningitidis, Mycobacterium tuberculosis) in preadolescent boys. In a few rare cases,1-3 streptococcal infections have been found to cause epididymo-orchitis as part of a local infection. However, all these cases occurred in preadolescent boys. There has been one report of a 17-year-old man with invasive group A streptococcal infection of the scrotum in the context of streptococcal toxic shock syndrome.4 Our case is unusual in that it occurred as a systemic illness in a 55-year-old man with haemochromatosis. This infection has not, to our knowledge, been previously described in association with haemochromatosis.5 1: Investigations Value Reference range Neutrophils 11.4 x 109/L 1.0–7.0 x 109/L C-reactive protein 98 mg/L < 3 mg/L Ferritin 205 μg/L 20-300 μg/L % Transferrin saturation 45% 20%–52% Streptococcal exotoxin AntiDNase B > 2560 < 320 Antistreptokinase > 20480 < 2560 Antistreptolysin O > 1200 < 300 2: Scrotal ultrasound images Left: Transverse image of the enlarged left testis (4.5 x 3 x 2 cm), with non-homogeneous echotexture and several small, rounded, echolucent cystic structures within the testis measuring 3 mm in diameter. The right testis showed similar, but less severe, features. Right: Longitudinal image of the enlarged left epididymis.

Sebastiaan J van Hal MB ChB · Robyn P Hardiman MB BS FRACP FRCPA

The US strain of West Nile virus could enter Australia, but we may be protected by the already present Kunjin virus Australia needs to consider the implications of the recent emergence and spread of West Nile virus in the United States, including the possibility of its spread to Australia. This development also raises questions about Kunjin virus, a subtype of West Nile virus, which already occurs widely in Australia. West Nile virus, a mosquito-borne flavivirus, was known to have a wide geographic range, extending from Africa through the Middle East to southern and eastern Europe and western Asia. The initial outbreak in New York city and adjacent counties in August 1999 resulted in 62 human infections and seven deaths of elderly patients.1,2 Genetic evidence suggests that the virus came from the Middle East. Over the next three years, it spread rapidly in the US, first in the north-east and then more widely, causing disease and deaths in humans, horses and birds.3 Birds, especially crows, were found to be responsible for both spread and maintenance of the virus in a natural cycle with culicine mosquitoes.3,4 By late November 2002, the virus had been detected in 43 states spanning the mainland US, with 3735 reported clinical cases and 215 deaths, almost all among the elderly.5 The virus had also spread to five provinces in Canada, with around 140 cases and two deaths. The speed of its spread was undoubtedly due to the presence of competent mosquito species and a large number of susceptible birds, and especially to a greatly increased propensity to spread in a virgin ecosystem. Before 1996, West Nile virus was known to cause high fever, chills, malaise, headache, backache, arthralgia, myalgia and retro-orbital pain, and, in about 50% of cases, a maculopapular rash,6 but neurological symptoms were uncommon. Since then, severe neurological illness, including encephalitis and meningitis, has been reported more frequently,6,7 together with an acute flaccid paralysis syndrome.6,8 Fatalities have generally been in the elderly. Although human acquisition is nearly always through the bite of an infected mosquito, unusual modes of transmission via organ transplantation,9 blood transfusion9,10 and possibly breastfeeding11 have recently been described in the US. West Nile virus is closely related antigenically and genetically to other members of the Japanese encephalitis serological group of flaviviruses, including Japanese encephalitis, Murray Valley encephalitis (MVE), and St Louis encephalitis viruses, and is almost identical genetically and immunologically to Kunjin virus.12 Kunjin virus, reclassified as a subtype of West Nile virus in 2000, is the most common flavivirus in Australia, occurring widely across northern Australia. Most infections with this virus are asymptomatic, but it causes occasional, mild febrile illness, similar to that traditionally described for West Nile virus, and rare cases of non-fatal encephalitis.13 It is closely related genetically to the West Nile strain in North America,1,2 both being members of West Nile lineage 1. However, unlike Kunjin virus, some recently isolated members of West Nile lineage 1 are known to cause fatal encephalitis in elderly patients,3,6,7 fatal disease in wild birds (in North America)3,14 and domestic geese (in Israel),15 and severe epizootics in horses, with significant mortality.7,13,14 In addition, recent experimental evidence has shown that the New York strain of West Nile virus is considerably more neuroinvasive than Kunjin virus.16 Could Kunjin virus mutate to be as virulent as recent West Nile strains seen in Europe and the US? Kunjin virus has been in our ecological system for many years without any apparent increase in virulence. Several mutations may be required to increase virulence substantially, and there seems little pressure to select for such mutations. Alternatively, could a more pathogenic strain of West Nile virus spread to Australia and, if it did, would it be able to establish itself in competition with Kunjin virus? West Nile virus has been isolated in Sarawak, Malaysia, and is endemic in western India; thus, it could conceivably spread slowly through the region. The virus is believed to have reached New York through carriage on an aircraft of an infected mosquito or an infected traveller with sufficient viraemia to infect a mosquito on arrival in the US. Similar mechanisms could allow its importation into Australia from the US, Europe or Africa. Although current disinsection procedures for aircraft are believed to minimise the first possibility, there is concern that an infected human traveller arriving in Australia might have sufficient viraemia to infect Australian mosquitoes. More information is urgently needed on viraemia levels during infection so that this risk can be properly assessed. Other routes of entry seem less likely. Although a horse infected with West Nile virus was recently imported into Australia from North America, viraemia levels in horses are believed to be insufficient to infect mosquitoes. Introduction of virus through migratory birds is doubtful because of the route and length of migration. Even if West Nile virus is introduced into Australia, it would have to compete with Kunjin virus for vertebrate hosts and vectors. Experience with other members of the Japanese encephalitis serogroup of flaviviruses suggests that they do not interfere with each other's ability to spread,12 despite the induction of cross-reacting antibodies. Thus, West Nile and Japanese encephalitis viruses coexist in western India, and MVE and Kunjin viruses coexist in Australia, while West Nile and St Louis encephalitis viruses appear to coexist in North America, and Japanese encephalitis and MVE viruses appear to coexist in Papua New Guinea. However, antibodies to Kunjin virus neutralise West Nile virus (and vice versa), and Kunjin virus is widely distributed over much of Australia, so it may prove more difficult for West Nile virus to find the susceptible vertebrate hosts it needs to become established or to spread rapidly. There is no treatment or vaccine available for West Nile infection, but people with prior exposure to Kunjin virus should be protected. Similarly, those exposed to other members of the Japanese encephalitis serological group, especially Japanese encephalitis and MVE viruses, may have limited protection against West Nile disease. The current Japanese encephalitis vaccine is unlikely to protect, although more research is needed to confirm this.17,18 Finally, could Japanese encephalitis virus spread in Australia as West Nile virus has done in the US? Japanese encephalitis virus has occurred in the Torres Strait of northern Australia nearly every year since 1995, and entered the Australian mainland in 1998.19,20 As Australia has the appropriate mosquitoes and avian and porcine vertebrate hosts for natural transmission cycles,20 it is likely that Japanese encephalitis virus will eventually become established here. However, the narrow range of bird species used by Japanese encephalitis virus as maintenance hosts (generally herons and egrets), the need for pigs as amplifier hosts, as well as the Australian ecosystem, climate and arid interior, would suggest that Japanese encephalitis virus is unlikely to match the spread of West Nile virus in North America. Migratory birds, wind-blown insects and rapid air transport of infected humans, animals and insects could all bring exotic pathogens into Australia. Identifying potential threats, maintaining aircraft disinsection and mosquito surveillance around major airports, as well as good internal surveillance, are important parts of the protection of human and animal health in this country.

John S Mackenzie BSc, PhD · Roy A Hall BSc, PhD · David W Smith FRCPA

To the Editor: While agreeing that sensible utilisation of pathology tests in emergency departments (EDs) is important, we are concerned that the article by Stuart et al1 might be misinterpreted to justify wholesale reductions in important diagnostic microbiological tests, particularly blood cultures. Stuart and colleagues imply they could safely reduce the number of blood cultures by 80%.1 Other local data have suggested a minority of blood cultures in the ED influence patient management.2 Confirmation of aetiology will be denied for patients by "rationalisation" of blood cultures in EDs. Although most pathogens are susceptible to broad-spectrum anti-microbial agents, widespread empiric prescribing of such agents in an era of increasing antimicrobial resistance is unwise. A recent Australian study evaluating blood cultures found that a third of patients with positive blood culture results were not clinically suspected to be bacteraemic.3 Furthermore, the Journal recently reported the emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA),4 and increasing resistance in Streptococcus pneumoniae.5 Missing MRSA or multidrug-resistant pneumococcal bacteraemia will result in adverse patient outcomes. What about missed cases of meningococcal disease, or typhoid fever, with their associated public health costs? Paradoxically, amid emerging antimicrobial resistance, we may become less aware of the problem. Furthermore, what about the infection control costs required to control the resultant outbreaks of multidrug-resistant organisms? Empiric broad-spectrum antibiotic prescribing, driven by failure to undertake important microbiological investigations, is bad medicine: It teaches everyone to guess the microbiological diagnosis, and, if you do not test, who can prove you wrong? Perhaps only when the patient presents to the tertiary referral hospital with therapeutic failure and evolving multisystem organ failure. It logically extrapolates to all patients getting vancomycin plus meropenem to ensure covering MRSA and resistant gram-negative bacilli. It inevitably drives resistance, which is increasing rapidly. It has never been subject to rigorous scientific scrutiny with cost-effectiveness studies. Moreover, the study by Stuart et al1 provides no data on readmission rates, lengths of stay, adverse events and rates of missed or incorrect diagnoses; the ED setting studied has limited generalisability; and United States guidelines, which may be inappropriate in the Australian healthcare context, were used to develop the diagnostic testing protocol. Might not reducing the ordering of some microbiological tests cause "spiralling therapeutic empiricism"? Might not the overall healthcare budget growth accelerate because of increased prescribing of expensive broad-spectrum antimicrobials?

Iain B Gosbell · Peter J Collignon · John D Turnidge · Christopher H Heath · Joan L Faoagali

The virus recognises the similarity of people on the planet. Scientists and policy makers must do the same. Helene Gayle (Director of the CDC's National Center for HIV, STD and TB Prevention) The AIDS epidemic is wreaking havoc and misery around the world and exposing the most awful inequalities and human frailties. In Australia, our population is relatively cocooned from this chaos (Box 1), although the conference heard of the established epidemic in our nearest neighbour to the north, Papua New Guinea, and the worrying emerging epidemic in Indonesia. Worldwide statistics can become numbing, causing human suffering to be ignored. Even for clinicians and researchers in the HIV/AIDS field, the magnitude of the problem is frequently too daunting to either comprehend or tackle in a useful way. However, the realities, and importantly the will, of good, hard-working people in the field were on display at the International AIDS Conference in Barcelona in July 2002. International AIDS conferences are amazing events, bringing the global issues surrounding HIV to the fore. They can be incredibly poignant, wonderfully motivating and equally frustrating all at the same time. Frequently, issues come into stark focus that challenge the status quo. Activists in the field of HIV/AIDS are not shrinking violets. Global access to anti-HIV medicationsWe must corner rich nations with the truth (Jeffrey Sachs, Economist and Advisor to the United Nations Secretary-General) The issue that galvanised many of the participants at Barcelona was the injustice of the lack of access to life-saving, but expensive, antiretroviral drugs in developing nations. In Barcelona, the momentum of providing global access to HIV/AIDS medicines gathered steam. The road to global access is likely to be long and full of pot-holes. The establishment of the Global Fund for AIDS, TB and Malaria provides a major focus for raising the estimated US$13 billion required per year to scale-up preventive approaches and to provide wide access to antiretroviral drugs in resource-poor nations. There was a real sense of holding political leaders accountable to ensure a more equitable future. In the words of Peter Piot, Executive Director of UNAIDS: Let's make the AIDS response truly political — let's bring forward the day when leaders who keep their promises on AIDS are rewarded with our trust, and those who don't, lose their jobs to those who will. Some political leaders were booed from the stage as the audience turned against their meagre or delayed responses to the epidemic. There have been successful pilot and expanding programs of antiretroviral treatment in several developing countries. There is growing unease that a poorly coordinated approach in the developing world will lead to the high levels of resistance to antiretrovirals now present in the developing world, squandering an opportunity to make a very major impact in these countries. Averting the errors made in antiretroviral therapy in the developed nations could potentially lead to more durable responses to antiretroviral therapy. These errors include serial monotherapy, sequential changes in the presence of imperfect HIV suppression, and decisions made to introduce new therapies on the basis of single equivalence studies measuring only short-term surrogate endpoints. The US-based AIDS Clinical Trial Group study, with 384 investigators, reported the first of the long-term strategy studies, in which outcome was based on time to first and second change of therapy in 980 individuals. This provides important information to guide treatment strategies across the globe. Essentially, the length of time to failure of first-line antiretroviral therapy was substantially longer with the initial combination of zidovudine, lamivudine and efavirenz, and the time to the second failure was substantially longer with either first- or second-drug regimens including zidovudine, lamivudine and efavirenz. No benefits of using four antiretrovirals over three were shown.1 For HIV-infected people with anti-retroviral resistance, the conference heard of encouraging efficacy reports of new drugs, such as tenofovir and T-20 (enfurvitide), as well as exciting preclinical information on integrase inhibitors. Unfortunately, the cost of these newer drugs will be prohibitive in developing countries. Not only are the treatment factors (regimen, the timing of commencement, affordable appropriate monitoring, support of adherence) important, but also support for training of healthcare professionals and commitment to ongoing funding for therapy is essential. The World Health Organization (WHO) report entitled Scaling up antiretroviral therapy in resource-limited settings continues to assist this process.2 Providing treatment for HIV is now thought to provide tremendous spin-offs for enhanced prevention. People with access to treatment are more likely to get tested for HIV infection and modify behaviour if found to be positive. Reductions in infectious virus load after treatment are likely to reduce transmission, although this is not yet definitely proven. Increasing use of medications is likely to drive global prices down. The problem of accurately taking all combination anti-retroviral therapy (adherence) continues to be shown to be a major factor affecting long-term success of therapy. To this end, an increasing number of studies of once-daily treatments are being reported. This offers practical options for improved adherence and intermittently delivered therapy (Box 2). No cureHIV treatments are most certainly not a cure. This was soberly brought home by a pioneering researcher in this field, Dr Robert Siliciano, from Johns Hopkins University, describing HIV as "intrinsically incurable". One problem lies with the dastardly ability of HIV to lie dormant in a population of cells called resting memory T cells. These cells are "designed to wait" for a lifetime to ward off previously encountered pathogens. It will prove very difficult to flush the virus out of these cells once it has taken hold. VaccinesThere is hope that a vaccine will eventually be developed that can prevent HIV infection around the world. Although this is one of the "star-wars", "high-tech" approaches to prevention, significant gains have been made in the last two years. There are three important considerations for an effective vaccine against HIV/AIDS — the vaccine must induce (i) T cell responses against virus-infected cells, (ii) neutralising antibodies against free virions, and (iii) mucosal immunity. Vaccines that induce high levels of T cell responses against HIV in animal model systems, although incapable of preventing infection altogether, are able to control viral replication for long periods. To prevent infection altogether, high levels of neutralising antibodies will be required. The induction of broadly reactive neutralising antibodies to HIV has proven very difficult, but there are now hints about potentially successful approaches. The virus is in the mucosal tissue during the first few days of infection. In 3–5 days the virus spreads and virus latency occurs. In 6–9 days the virus has spread systemically. An effective vaccine needs to work at the mucosal site of infection before systemic dissemination occurs. One major obstacle against engineering an effective vaccine is that HIV is capable of escaping both neutralising antibodies and cellular immune responses. Furthermore, there is no definitive HIV marker for protection. There were mixed reports on whether a vaccine could induce immunity across different subtypes of HIV-1 — cross-subtype T cell immune responses exist for T cell-inducing vaccines, but there are no vaccines offering a breadth of neutralising antibodies. The vaccine world is waiting with bated breath for the outcome, due to be released early in 2003, of the world's first efficacy trials in humans of HIV vaccines using envelope protein approaches with alum as the adjuvant. These trials have been conducted efficiently, albeit not without controversy, in 2500 subjects in Thailand and 5000 subjects in the United States and elsewhere. Controversies in these trials have included whether it was justifiable to proceed to human efficacy trials with vaccines that performed poorly in some preclinical studies; the provision of clean injecting equipment to trial participants; and the lack of provision of antiretroviral treatment to subjects who become infected during the trial. Encouraging reductions in risk behaviour have occurred during these efficacy trials; however, a sufficient number of seroconversions have occurred which, when the data are unblinded, should provide a robust analysis of efficacy. One final important point emphasised was that vaccine research should be complementary to, and not in competition with, therapeutic research. Other prevention approachesThe definition of insanity is doing the same thing over and over again and expecting a different result. Rita Brown (arguing for innovative programs to prevent the spread of HIV). In addition to enhanced standard prevention approaches of education, behavioural change, condoms (both male and female versions) and others, further exploration of biomedical approaches to prevention are being evaluated. Male circumcision appears to provide considerable protection from HIV, and observational studies and trials are now under way to evaluate this approach more rigorously in developing countries. Treatment of other sexually transmitted infections is now being evaluated (eg, control of herpes simplex with aciclovir) as a means of preventing HIV acquisition and transmission. Non-occupational postexposure prophylaxis with antiretrovirals is now common in many developed countries, although gathering data on its efficacy has been difficult. The spectre of pre-exposure prophlyaxis with antiretrovirals was also raised. Widespread use of antiretrovirals as pre-exposure prophylaxis has worrying implications for the development of antiretroviral resistance, but, if infection was completely prevented, resistance would not occur. Call for actionA recurring message at the conference was the need for decisive action now. As Helen Gayle said, quoting an African proverb: The best time to plant a tree was 20 years ago; the next best time is now. 1: Global distribution of the AIDS epidemic in 2001 Numbers of people living with HIV at the end of 2001 (and, in parentheses, those newly infected with HIV during 2001) as estimated by UNAIDS and WHO. Data available at: http://www.unaids.org/barcelona/presskit/graphics.html#global.htm (accessed October 2002, no longer available). 2: Once-daily HIV medications to overcome problems of adherence Currently available once-daily antiretroviral medications in Australia/USA Efavirenz Tenofovir Didanosine Ritonavir-boosted amprenavir Antiretroviral medications suggested for future development as once-daily medication Nevirapine Abacavir Other ritonavir-boosted protease inhibitors Atazanavir 3TC FTC T-1249 (fusion inhibitor) Stavudine XR (slow-release version of stavudine) 3: More quotable quotes from the Barcelona AIDS conference Helene Gayle (Director of the CDC's National Center for HIV, STD and TB Prevention, and of the Bill and Melinda Gates Foundation HIV/AIDS and Tuberculosis Program:When will justice come to Athens? Justice will come when those that are not injured are as indignant as those that are (quoting the Greek historian Thucydides). Suniti Solomon, Director, Centre for AIDS Research and Education, India:In Zambia, a widow must cry with only one eye (describing how women whose husbands die of AIDS must keep an eye on their assets, which are often seized by relatives of the deceased). Paul Farmer, Professor of Medical Anthropology, who has established a modern medical centre in a squatter settlement in central Haiti, and introduced antiretroviral treatment:Now my children are not ashamed to be seen with me (quoting a Haitian patient describing the reduction in stigma since starting antiretroviral treatment).

Stephen J Kent MB BS, MD, FRACP · C Jane Dale BSc, PhD · Anne M Mijch MB BS, FRACP

The risk of contamination of drinking water supplies with microbial pathogens is minimised by modern approaches to water management, but continues to be the major public health concern. Chemical contaminants usually pose little health risk except at very high levels, but debate continues over the potential adverse health effects of low-level, chronic exposure to compounds such as disinfection byproducts. Recreational water contact can be associated with adverse health outcomes either from microbial infections or exposure to cyanobacterial toxins. Environmental issues such as increasing salinity and global warming are likely to affect the sustainability of our current drinking water supplies and increase the threat of waterborne disease outbreaks. New technologies, use of alternative water sources, such as rainwater tanks, water reuse and restrictions will undoubtedly be part of the solution to our diminishing water resources, but have the potential to introduce new health threats.

Karin Leder FRACP, MPH, DTHM · Martha I Sinclair PhD · John J McNeil FRACP, PhD, FAFPHM

About four million cases of foodborne infectious disease occur annually in Australia; new foodborne pathogens, such as enterohaemorrhagic Escherichia coli, are emerging. Climate change, combined with changes in how we produce and distribute food and how we behave as consumers, have the potential to affect foodborne disease in the coming century. Foodborne disease outbreaks are now more far-reaching (and sometimes global) due to modern mass food production and widespread food distribution. There are strong seasonal patterns for Salmonella and Campylobacter infection in Australia. Global warming may increase the incidence of infections, such as salmonellosis, and diseases caused by toxins, such as ciguatera.

Gillian V Hall MB BS, PhD · Rennie M D'Souza MB BS, PhD · Martyn D Kirk MAppEpid

Background: In 1941, a Sydney ophthalmologist, Norman McAlister Gregg, correctly identified the link between congenital cataracts in infants and maternal rubella early in pregnancy. Fifty of Gregg's subjects with congenital rubella, born in 1939–1944, were reviewed in 1967 and again in 1991. We reviewed this cohort in 2000–2001, 60 years after their intrauterine infection.Methods: The subjects underwent full clinical assessment, plus pathology tests, an ophthalmological and cardiological review (including electrocardiography and echocardiography) and HLA histocompatibility testing.Results: Since they were first seen in 1967, 10 have died (cardiovascular causes [4], malignant disease [4], AIDS [1], and hepatitis C-related cirrhosis [1]). All surviving men came for review (19) and 13 women (eight women declined). Echocardiography showed mild aortic valve sclerosis in 68%. The prevalence of diabetes (22%), thyroid disorders (19%), early menopause (73%) and osteoporosis (12.5%) was increased compared with the Australian population; 41% had undetectable levels of rubella antibodies. The frequency of HLA-A1 (44%) and HLA-B8 (34%) antigens was increased, and the haplotype HLA-A1, B8, DR3, said to be highly associated with many autoimmune conditions, was present in 25%.Conclusions: This cohort of people with congenital rubella has illuminated our understanding of viral teratogenesis.

Jill M Forrest MD BS · Fiona M Turnbull MB, ChB · Gary F Sholler MB BS, FRACP · Richard E Hawker MB BS, FRACP · Frank J Martin FRANZCO, FRACS · Margaret A Burgess MD, FRACP · Trevor T Doran MSc, PhD

The death of a friend solved a centuries-old, oft-fatal mystery My doctrine is produced in order to banish the terror from lying-in hospitals, to preserve the wife to the husband, and the mother to the child... — Ignaz Semmelweis, 1861 Today, a very large proportion of women giving birth receive antibiotics, potent and sometimes in combination, during their accouchement. Routine prophylaxis is widely accepted for caesarean sections, which account for 20%–25% of deliveries.1 Of course, any pregnant woman presenting with an obvious infection will automatically receive an antibiotic. Further, so will most pregnant women with membranes ruptured for any length of time, either before or after labour begins, and any woman in labour with a raised temperature. There is also a more relaxed approach to many former midwifery routines — for example, the abandoning of masks and gowns and the admission of several support people to the delivery scene — which could diminish both younger obstetricians' and midwives' appreciation of the potentially deadly risk of puerperal infection. However, until relatively recently in developed countries, and still in many developing countries, puerperal sepsis was and is a killer.2 Fatal feverImmediately postnatally, the placental site is a large open wound — easily invaded by ascending bacteria. For thousands of years, it was recognised that puerperal women were at risk of a fever that could be fatal. The Hippocratic writings contain references to childbed fever, as do some Hindu texts dating back to 1500 bc.3 Moreover, the potential for birth attendants to initiate such infections seems to have been comprehended by some of the ancient writers, including the Greek physician Soranus, and the Hindus, since advice on hygiene for birth attendants was offered.3,4 Triptych showing the Hôtel Dieu in Paris, about ad 1500. The comparatively well patients (on the right) were separated from the very ill (on the left). Note there were always two patients to a bed. Nevertheless, in ancient and medieval times, mortality from puerperal sepsis was apparently relatively low, as women generally gave birth at home. Peculiar to the puerperium?The 17th century saw the establishment of "lying-in" hospitals in many European cities. While these institutions were, in some ways, an advance — in particular, by relieving obstructed labour with forceps or intrauterine manipulation — the crowding of patients, frequent vaginal examinations and the use of contaminated instruments, dressings and bedlinen spread infection in an era when there was no knowledge of antisepsis. The first recorded epidemic of puerperal fever occurred at the Hôtel Dieu in Paris in 1646. Subsequently, maternity hospitals all over Europe and North America reported intermittent outbreaks, and even between epidemics the death rate from sepsis reached one woman in four or five of those giving birth.5 Numerous bizarre theories as to the cause of childbed fever were expounded — among them that it was due to a "miasma", or the labouring woman's disturbed state of mind, or mechanical pressure from the distended uterus. Certainly, childbed fever was universally regarded as a condition peculiar to women in labour.6 Sepsis suspectedContagion as the basis for childbed fever was first suspected by a number of British physicians in the late 18th and early 19th centuries.7 The name of Thomas Watson, Professor of Medicine at King's College Hospital, London, is not well known, but in 1842 he wrote: "Wherever puerperal fever is rife, or when a practitioner has attended any one instance of it, he should use most diligent ablution." Watson recommended handwashing with chlorine solution and changes of clothing for obstetric attendants — everything, he said, "to prevent the practitioner becoming a vehicle of contagion and death between one patient and another." Unfortunately, Watson's advice seems to have been largely ignored by obstetric practitioners of the time — the contagion theory is completely absent from contemporary obstetric texts.7 Oliver Wendell Holmes Across the Atlantic, in Boston, Dr Oliver Wendell Holmes — pathologist, physician and president of the Boston Society for Medical Improvement — developed an interest in the condition after two related cases were presented to his society. A physician and a medical student both died of septicaemia after performing an autopsy on a woman who died of puerperal fever. Holmes read the existing literature, and became convinced that the condition was highly contagious, and that doctors, nurses and midwives were the active agents of its spread. He began to speak and write on the subject, and in 1843 published his classic essay The Contagiousness of Puerperal Fever.8-10 The essay contains eight rules for the obstetrician, which included not only handwashing and changes of clothing, but also the avoidance of autopsies if obstetric cases were being managed. Holmes' conclusions were ridiculed by many of his prominent contemporaries. For example, Charles Meigs, a well-known obstetrician, was incensed at the suggestion he may himself be transmitting disease. "Doctors," he said, "are gentlemen, and gentlemen's hands are clean."10 Connection comprehendedMeanwhile, in Vienna, Dr Ignaz Semmelweis, a native of Hungary, was beginning a life-long obsession with finding the cause of, and preventing, puerperal fever. However, knowing no English, and far from North America, Semmelweis was unaware of the work of Holmes. Ignaz Semmelweis In 1844, Semmelweis was appointed assistant lecturer in the First Obstetric Division of the Vienna Lying-In Hospital, the division in which medical students received their training. He was appalled by the division's high mortality rate from puerperal fever — 16% of all women giving birth in the years 1841–1843. In contrast, in the Second Division, where midwives or midwifery students did the deliveries, the mortality rate from the fever was much lower, at about 2%. Semmelweis also noted that puerperal sepsis was rare in women who gave birth before arriving at the hospital.6,11 Over the next few years, Semmelweis studied and rejected numerous hypotheses. He did note that medical students and doctors from the First Division performed autopsies each morning on women who had died in the hospital the previous day and that midwives were not required to perform such autopsies. However, he did not immediately appreciate the connection between the two observations.6,11 In March 1847, Jakob Kolletschka — professor of forensic pathology, colleague and friend of Semmelweis — died of septicaemia after sustaining an accidental wound to the hand during an autopsy. On reading the report of Kolletschka's autopsy, Semmelweis was struck by the similarity of the pathological findings to those of women who had died of puerperal fever. He later wrote: "Suddenly a thought crossed my mind: childbed fever and the death of Professor Kolletschka were one and the same. His sepsis and childbed fever must originate from the same source . . . the fingers and hands of students and doctors, soiled by recent dissections, carry those death-dealing cadavers' poisons into the genital organs of women in childbirth . . .".6,11,12 Semmelweis began experimenting with various cleansing agents and, from May 1847, ordered that all doctors and students working in the First Division wash their hands in chlorinated lime solution before starting ward work, and later before each vaginal examination. The results were extraordinary — the mortality rate from puerperal fever in the division fell from 18% in May 1847 to less than 3% in June–November of the same year.11 Doctrine dismissedLike Holmes, Semmelweis found that his conclusions did not receive immediate acclaim from his colleagues and superiors. Indeed, he was treated with scepticism and ridicule by many in the Viennese and wider European medical establishments, including his own professor, Johann Klein. In 1849, Semmelweis' contract with the Lying-In Hospital was not renewed and he returned to Hungary, joining the University of Pest. He presented his findings to the Medical Society of Vienna in 1850. They were not well received, other opponents at that time including the famous pathologist Rudolph Virchow and the prominent obstetrician Friedrich Scanzoni. Semmelweis did not publish his observations until 1861; again, they were greeted dismissively. Embittered, Semmelweis wrote a series of "open letters" to his former professors, accusing them — rightly, as it turned out — of being "medical Neros" and "murderers".11,12 Sadly, his last years were affected by depression and mental disturbance. In July 1865, he was committed to a psychiatric institution in Vienna, and died there two weeks later — ironically, probably from septicaemia following a cut to a finger.3,6 Acceptance of antisepsisParadoxically, within a few years of his death, Semmelweis' doctrine began to be accepted by the wider medical community. In 1874, Billroth demonstrated streptococci in pus from wound infections, and in 1879 Louis Pasteur identified the haemolytic streptococcus in the blood of a woman with puerperal sepsis.3 Joseph Lister, learning of Pasteur's work and germ theory, began to apply antiseptic principles to the practice of surgery, with a dramatic fall in postoperative deaths from infection. As with Semmelweis', Lister's ideas were also greeted with scepticism and it took nearly 30 years for "Listerism" to be universally accepted by medical practitioners.13 By the end of the 19th century, the need for obstetric asepsis was well appreciated. An authoritative text of 1905 gives detailed instructions for the personal hygiene of physicians and nurses attending confinements and instructions on the performance of internal examinations. The importance of "inculcating in the student the principles of obstetrical cleanliness, mechanical and chemical" is emphasised. The need for meticulous antiseptic care during operative vaginal deliveries and manipulations — more frequent then than now — is reiterated.14 Australian medical practitioners were apparently quick to follow the lead of their overseas colleagues in the application of hygienic measures in obstetrics, and of self-regulation when puerperal fever occurred in their practices. Most stopped attending midwifery cases for a time after one or two deaths among their patients.15 Surprisingly though, despite the new understanding of the importance of antisepsis, puerperal sepsis still occurred frequently in developed countries in which figures were kept. It appears the principles of antisepsis were not universally applied. In England and Wales, in the period 1870 to 1890, the maternal death rate in hospital births was around 1 : 20, of which about 40% were due to infection. In the United States, in the 1890s, 20 000 women a year died in childbirth.14,16,17 In New South Wales, in 1894–1896, among confinements of married women, both at home and in hospital, the government statistician found a death rate of 1 : 148, and he commented on the negligence of medical men in filling the certificates required by law. Up to that point, causes of death had been supposedly accurately recorded for more than 40 years, but, in fact, the puerperal nature of fatal infections in women was frequently omitted.14,15 Globally, the most common and most feared infecting organism at the time was the Group A haemolytic streptococcus, whose virulence appears to have diminished in recent years, possibly due to improved socioeconomic conditions and the use of antibiotics. Normally found on the skin, in the nose and throat, and in the vagina, as well as in skin lesions, the streptococcus was introduced into the genital tract during examinations and deliveries. Lacerations, blood loss and exhaustion from prolonged labour increased the possibility of postpartum infection. Staphylococci, gonococci, coliforms and other bowel flora, as well as anaerobes, were less likely culprits, but have assumed greater importance in recent years, as have Group B streptococci.3,7,15 Debating deliveriesIn Australia overall, as elsewhere overseas, the maternal mortality rate (MMR) actually remained steady from 1900 until the late 1930s (5.95 per 1000 women delivered in 1903; 5.13 in 1933). Among developed nations, the United States had the highest MMR and the Netherlands and Scandinavia the lowest, although there were some individual hospitals with remarkably low rates, including the Rotunda in Dublin, Ireland, and Crown Street Women's Hospital in Sydney, Australia.15,17 Causes of the continuing fatal role of puerperal sepsis were widely debated. The medical profession tended to blame untrained midwives, and moved towards their training and registration, which was achieved by the 1930s. Some attributed the rates of sepsis to high levels of interference in labour and delivery, especially forceps deliveries. In Australia, the "lodge" system of practice — whereby families purchased medical services through lodge or friendly society membership — was held to blame. Busy general practitioners contracted under this system were allegedly likely to try to conduct confinements hurriedly.15-17 There were moves both to increase instruction in obstetrics for general practitioners and to encourage specialist obstetricians to do deliveries.15 Antibiotic arsenalAfter 1935, the situation improved rapidly in developed countries. Early that year "a startling therapeutic success" was announced by Domagk in Germany — the prevention of septicaemia in mice experimentally infected with streptococci after the administration of prontosil, a sulfonamide dye.18 In June 1936, Colebrook and Kenny, in a landmark paper, reported their success in treating established puerperal sepsis in women using prontosil — the death rate in apparently similar cases dropped from around 27% to 8%. Colebrook and Kenny wrote (cautiously): ". . . the very low death rate, taken together with the spectacular remission of fever and symptoms observed in so many of the cases, does suggest that the drug has exerted a beneficial effect".18 History was to prove them correct, and in 1939 Domagk was awarded the Nobel Prize in Medicine and Physiology for his work. Prontosil and other sulfonamides were followed by penicillin, to which streptococci causing puerperal sepsis still remain sensitive, and the arsenal of antibiotics used for all other forms of postpartum fever today.3,19 Today, in Australia, deaths from puerperal sepsis are extraordinarily rare (the MMR is currently about 0.1 per 1000 births).2 However, infection and fever are not rare, and the microbes causing them are omnipresent. In caring for pregnant women, especially the many who have some intervention in labour or delivery, we would be wise to reflect that it is only the use of increasingly complex antibiotic regimens which prevents a return to "the terror of the lying-in hospitals".

Caroline M De Costa FRANZCOG, FRCOG

To the Editor: These two cases, which occurred many years ago, illustrate a useful clinical sign in the diagnosis of tetanus. An elderly man was admitted to hospital after crushing his finger in a stable door. He commented in passing that when he whistled across the park to his wife that morning, she had not heard him. However, she had heard him the previous two mornings. He was a professional whistler on the radio and, when asked, still appeared to produce a good strong whistle. As it is the high pitch that carries long distances, I pondered the causes of selective pitch loss. I suspected the "risus sardonicus" of tetanus. He was subsequently confirmed to have tetanus and survived. Years later, a middle-aged woman with right hypochondral pain and presumed cholelithiasis presented to a country hospital for a cholecystogram. I chatted to her about her bandaged hand — she said that she had cut it on a jam tin in her house, but that her general practitioner was treating it, and all her vaccinations were up-to-date. Some hours later she complained that her abdominal pain was worse and had moved. I believed that the pain was probably related to movement of gallstones, but was more interested in her hand wound, of which she was dismissive. I asked her to whistle. It was a good whistle, but she commented, "It's not my whistle, I whistle the cows into the bales." Recalling my previous patient with the altered whistle, I diagnosed tetanus and arranged her urgent transfer to a consultant at Sydney Hospital (Sir Kenneth Noad). Indeed, she did have tetanus, and developed laryngeal spasm requiring emergency tracheotomy and 2.5 weeks in a respirator. Sir Kenneth later thanked me for saving the patient's life. The alteration of a person's whistle in tetanus can be explained as an early effect of the increased tone in facial muscles, which causes the classic risus sardonicus. As tetanus toxin must travel from peripheral nerve terminals to the nerve-cell body in the brainstem or spinal cord to exert its effects, muscles of the jaw, face and head, with their shorter axonal pathways, are often involved before those of the trunk and extremities.1

Eric R Dunn

Chlamydia pneumoniae has been detected in atherosclerotic plaques, while seropositivity to this organism confers a slightly increased risk of coronary events. However, no aetiological link has been established; a major difficulty when investigating this link is the lack of a gold standard for diagnosing chronic vessel infection. The outcomes of case–control studies and prospective trials of macrolides in treatment and prevention of cardiovascular disease have been ambiguous but suggest a short-term preventive effect. Whether this is due to the antimicrobial or anti-inflammatory activity of the macrolides is unknown. Larger and longer prospective trials currently under way may provide better insight into the association of C. pneumoniae with cardiovascular disease. At present, there is no justification for treating cardiovascular disease with antibiotics.

Mikkel M Larsen BSc · Birgitte Moern MD, PhD · Paul L Andersen MD, DMSc · Lars J Ostergaard PhD, DMSc · Andrew Fuller FRACP

Clinical record In 2001, an outbreak of Bordetella pertussis infection occurred in a hospital special care nursery. The index case, Parent A, had a two- to three-week history of non-productive cough without paroxysms, whooping or vomiting. She was admitted to hospital in labour and gave birth to Baby A on Day 0 in early January 2001. The baby was born four weeks prematurely and remained in the special care nursery for 15 days. The mother spent several hours there each day handling her infant and occasionally assisted with the care of infants in adjoining cots. Serum taken 19 days after she developed cough was negative for Bordetella pertussis IgA and IgM and equivocal for IgG (Figure) by enzyme-linked immunosorbent assay (ELISA). On Day 15, Baby B (in the cot adjacent to Baby A) developed a cough and respiratory distress. Initial investigations did not reveal a cause. A nasopharyngeal aspirate collected on Day 23 was positive for B. pertussis by direct fluorescent antigen testing. On Day 18, a nurse who had cared for Baby A developed a cough. Her serum was positive for B. pertussis IgA on Day 31 by ELISA; she commenced roxithromycin therapy. On Day 31, serum collected from Parent A was positive for B. pertussis IgA. On Day 39, Baby A developed a respiratory illness despite a seven-day prophylactic course of erythromycin. A nasopharyngeal aspirate was positive for B. pertussis by polymerase chain reaction (PCR) on Day 43. Both received erythromycin. On Day 41, a nasopharyngeal aspirate collected during contact tracing from Baby C (in the nursery from Day 0 to 6) grew B. pertussis. She had not received chemoprophylaxis and had a mild cough. She was treated with erythromycin. Contact tracing Contact tracing of infants, parents and staff was undertaken. The incubation period of pertussis is six to 21 days, and is generally less than 10 days.1 The parents of all 19 babies who had been in cots adjoining Baby A were notified, and erythromycin prophylaxis was recommended. Eleven babies received prophylaxis. Parents of other babies in the nursery were contacted and advised to notify the hospital if they or their babies developed a cough over the following 21 days. No further cases were identified. Fifty-three staff with close contact with the cases were screened using direct fluorescent antigen testing of nasopharyngeal aspirates and serum IgA testing. Thirty-three received antibiotic prophylaxis. No staff had illness consistent with acute pertussis or developed infection, as shown by nasopharyngeal and serum IgA tests. There were 10 339 notifications of pertussis in 1999– 2000 in Australia.2 People aged 15 years and over comprised 62% of these notifications.2 Studies indicate that 12% to 32% of cases of prolonged cough (over two weeks' duration) in adolescents and adults are due to B. pertussis.3 Recent articles highlight reasons for the apparent shift in disease burden.3-6 Although adolescents and adults are the primary reservoir of the disease and the main source of infection in infants and unvaccinated children, pertussis often goes unsuspected in these age groups.3,4,7 Pertussis in adults is difficult to detect clinically. Delays and errors in diagnosis occur because the presentation is commonly mild or atypical, and may be asymptomatic.7 This may be a result of immunological recall. As past vaccination or illness does not confer lifelong immunity to pertussis, reinfection is common.8 Detection in adults is further impeded by the poor sensitivity of culture and serological tests,1 particularly if performed several weeks after onset of cough.6 Polymerase chain reaction of nasopharyngeal swabs or aspirates improves detection.6 Deaths from pertussis average one per year in Australia, and almost all involve neonates and unvaccinated infants.2 These groups acquire pertussis in a range of settings, including hospitals;9,10 parents, visitors and healthcare staff are a source of nosocomial outbreaks.7 During the events described here, there was no concurrent epidemic of pertussis in the community (Dr B McCall, Director, Brisbane Southside Public Health Centre, personal communication). Hospitalised infants exposed to pertussis are at high risk of morbidity and mortality, as maternal antibodies provide inadequate protection, while infants less than four weeks old are too young to commence vaccination.11 While erythromycin is the prophylaxis of choice,11 it has been associated with hypertrophic pyloric stenosis in neonates.12 Preventing nosocomial transmissionB. pertussis is spread via mucosal contact with infectious respiratory droplets and secretions.13 We suggest the following standard and transmission-based infection control precautions to protect hospitalised infants: limit access of staff and visitors to nurseries; provide adequate space between open cots (at least one metre); discourage parents from contact with infants other than their own; and perform hand antisepsis before entering the nursery and before and after patient contact. Surgical masks are chiefly designed to protect the wearer from exposure to blood and body fluids; it is suggested that they may also reduce the opportunity for onward transmission of infections spread via large droplets.13 Other important measures include educating staff and visitors to report coughs, diagnosing their aetiology, and providing treatment and prophylaxis. A diagnosis of pertussis can be confirmed by nasopharyngeal aspirate (culture, direct fluorescent antigen testing or PCR) or serological testing (IgA).7 Erythromycin is the treatment and prophylaxis of choice at all ages.11 Targeted booster vaccination of parents and healthcare workers in contact with infants has been recommended, although not universally adopted.3-6 An acellular pertussis vaccine is available for this purpose, but its efficacy and duration of protection remain to be determined.3-5 Australia's pertussis immunisation schedule is restricted to infants and young children.11 Infection control measures are important because of the difficulty in prohibiting all people with coughs from entering hospital nurseries, and the cost implications of vaccinating all adults in contact with infants. Lessons from practice Pertussis should be considered in adults and older children with a cough lasting over two weeks regardless of a past history of pertussis vaccination or infection. If pertussis is suspected, a nasopharyngeal aspirate or swab should be tested by polymerase chain reaction. Serological testing may also be useful when symptoms have been established for longer than two weeks. Adolescents and adults are the primary reservoir of the disease and the main source of infection in infants and unvaccinated children. Hospitalised infants are at high risk for morbidity and mortality from pertussis. Infection control measures are paramount, and targeted vaccination of adults should be considered.

Natalie M Spearing BSN, MBA · Robert L Horvath FRACP · Joseph G McCormack FRCP, MD, FRACP

In October 2000, a 10-year-old Aboriginal boy from the Darwin region of the Northern Territory was referred to hospital with a 24-hour history of abdominal pain, initially generalised, but then localising to the right iliac fossa. The pain was accompanied by occasional vomiting, but no fever or diarrhoea was noted. At laparotomy, a gangrenous, unruptured appendix was removed. Postoperatively, the patient made a good recovery. Neither he nor any family members had travelled outside the Northern Territory. Histological sections of the surgical specimen showed changes typical of acute suppurative appendicitis. Closer examination, however, revealed numerous round-to-oval structures resembling trophozoites (see Box). When the possibility of invasive amoebiasis was raised, staining of the section with Entamoeba histolytica-specific sera confirmed the diagnosis. E. histolytica serology was negative. DiscussionE. histolytica is a protozoan parasite of humans that causes infectious colitis and amoebic liver abscess. It has recently been recognised that invasive disease is caused exclusively by the species E. histolytica, while the morphologically identical species E. dispar exists in the colonic lumen as a harmless saprophyte.1 Patients with invasive amoebiasis living in Australia and other developed countries generally acquire the infection outside their country in a region where the pathogenic species is known to be endemic. While cases of amoebiasis in Australians who have not travelled overseas have been reported,2-6 all except one pre-date the recognition of pathogenic and non-pathogenic species, and in none was the primary source identified. Isolated appendicitis due to E. histolytica is a rare condition. Even in regions where the organism is endemic, it causes less than 1% of cases of appendicitis.7 The diagnostic method of choice for amoebic colitis is testing for parasite antigen in stools.1 In this case, for the first time, the species-specific antibody normally used in the stool antigen test was adapted for immunohistochemistry and confirmed E. histolytica infection. Possible alternative methods for confirming the diagnosis include the polymerase chain reaction (PCR) or detection of E. histolytica-specific antibodies or parasite antigen in patient serum.1 However, PCR is not readily available outside research laboratories. The sensitivity of the E. histolytica antibody test in intestinal disease is 52%, a likely explanation for the negative serological test. It is curious that no outbreaks of the readily identified and much more common manifestations of this infection, namely amoebic colitis and amoebic liver abscess, have been recently reported in northern Australia. The potential public health significance of a case of proven autochthonous infection in an Australian population is reinforced by its high transmissibility in settings where hygiene may be suboptimal.8 Furthermore, there is a well documented possibility of prolonged latency between infection and the development of invasive disease.1 Both these factors support the merit of selective screening and appropriate treatment of at-risk contacts if invasive disease is detected. The use of new diagnostic techniques, such as the adapted staining method we used, will enable a more accurate determination of the endemicity of E. histolytica in Australia. Entamoeba histolytica in an inflamed appendix A: Periodic acid–Schiff stain, showing trophozoites (arrowed) within an inflammatory infiltrate. B: Immunoperoxidase stain of trophozoites (arrowed) using E. histolytica-specific sera. Note the surrounding necrotic tissue.

James S McCarthy FRACP MD · David Peacock MB BS · Kevin P Trown FRCPA · Patrick Bade FRACS · William A Petri Jr MD · Bart J Currie FRACP

There are few good-quality studies of the effectiveness of antibiotic treatment of proven group A streptococcal (GAS) pharyngitis in children; available data suggest that antibiotics may reduce symptom duration. While there is limited justification for antibiotic treatment of GAS pharyngitis to prevent acute rheumatic fever in non-Indigenous Australians, there is no justification for routine antibiotic treatment of all patients with sore throat. Two strategies are open to clinicians: not to treat GAS pharyngitis with antibiotics, in which case no investigations should be done; or to treat cases of sore throat with clinical features that suggest GAS, in which case diagnosis should be confirmed with a throat swab, and penicillin started while awaiting the result. Penicillin should be discontinued if the swab is negative, or continued for 10 days if it is positive for GAS. Surveillance of GAS infections and acute rheumatic fever is needed in Australia, as are further studies of effectiveness (including cost-effectiveness) of antibiotic treatment of proven GAS pharyngitis.

Margaret H Danchin MB BS · Nigel Curtis PhD, FRACP · Jonathan R Carapetis PhD, FRACP · Terence M Nolan PhD, FRACP

The most direct way to reduce percutaneous injuries is to make devices safer In this issue of the Journal, Whitby and McLaws (page 418) provide a thorough epidemiological account of occupational exposure to bloodborne pathogens by hollow-bore needles in one hospital.1 More studies such as theirs are needed in Australia, where there has been relatively little attention focused on this issue, as indicated by the few references to studies by Australian investigators cited in their article. As an American I find this surprising, because many successful prevention programs introduced in Australia have earned the admiration of public health professionals in other countries. Three examples come to mind: laws requiring seatbelt use and advanced passenger protection in motor vehicles; progressive HIV prevention programs; and programs to prevent ultraviolet light exposure and skin cancer. I am among the admirers of Australia's strong prevention record. In light of these progressive programs, how might one explain the relative neglect in Australia of such a serious occupational risk as bloodborne pathogen exposure? Some answers may be extrapolated from the United States, where I have observed a culture of self-sacrifice among healthcare professionals that compels them to place self-interest at the bottom of their priority scale. I have also seen administrators make healthcare worker safety a low priority when protective measures for their employees require a financial commitment. Finally, resistance to new prevention policies for healthcare workers is likely to be strongest where there is a lack of surveillance data. This is the "no data, no problem" syndrome. In Australia, an awareness of the significance of the problem of exposure to bloodborne pathogens is necessary before a national commitment can be made to its solution. Percutaneous injuries are the most frequent type of injury sustained by healthcare workers, and the most life-threatening.2 This remains true despite important advances, including the availability of the hepatitis B vaccine and post-exposure chemoprophylaxis for HIV-exposed healthcare workers.3,4 Therefore, I am convinced that the only choice is to accept the responsibility of caring for our caregivers — in Australia and elsewhere. The first step towards overcoming neglect is documenting the problem. The report by Whitby and McLaws provides a fine example, on a small scale. With reported annual percutaneous injury rates of 4–15 injuries per 100 full-time-equivalent staff,1 and device-specific injury rates occurring usually in the range of 1–20 injuries per 100 000 devices used,5 the participation of numerous institutions and a long term commitment are required to maintain a database that can guide and sustain large-scale prevention programs.6,7 Active surveillance programs support strong policy initiatives, as has been seen in the US, where surveillance data have supported new regulations, guidelines and advisories issued by our government agencies, as well as state and national legislation.8,9 Widespread surveillance should become a national goal for Australia. There is a global network of countries in Europe, Asia and South America with advanced surveillance programs eager for collaborative exchange. Surveillance data reveal the causes of bloodborne pathogen exposures and they lead to conclusions that are difficult to ignore. Surveillance data from the International Health Care Worker Safety Center, University of Virginia, from 1996 to 2000 (84 hospitals, 23 243 injuries) show that 98.5% of percutaneous injuries sustained by healthcare workers were caused by sharp medical devices (exceptions include injuries from windshield glass, teeth, fingernails and bone fragments). Therefore, the most direct route to preventing percutaneous injuries is to make injurious devices safer to handle. I find it incredible that the debate still persists whether educational programs or safer devices should be the preferred method of protecting healthcare workers. If you asked a soldier dispatched to the frontlines of battle whether he would prefer a protective shield or an educational poster, there would be no need for discussion. Let us move quickly to get protective devices into the hands of healthcare workers, while providing the best educational methods to support the use of safer technology. The lack of data on the effectiveness of safety devices is often raised as a barrier to their adoption. Although there are several studies demonstrating the efficacy of safety-engineered needle devices, there nevertheless remains a need for further well-designed clinical trials as new and safer technology comes into the market place.10-11 But where data are lacking on potentially life-saving technology there should also be a responsibility to collect those data, rather than merely rejecting the technology by reason of their absence. But we should also not dismiss the use of common sense in weighing the potential safety impact of many safer devices: intravenous infusion systems with needleless access ports and needleless line connections cannot cause needlestick injuries (as long as one does not override the system and use needles with them); plastic capillary tubes and vacuum tubes all but eliminate the possibility of lacerations; blunt-tipped suture needles do not cause needlestick injuries. Not every device category requires a clinical trial to prove a reduction of injuries, especially if that device eliminates a needle or sharp item. Another area of time-consuming debate is whether safety devices are cost-effective. We now have a law in the US, the first in the world, requiring healthcare employers to provide safety-engineered devices for the prevention of percutaneous injuries, without consideration of their financial impact on individual healthcare facilities.9 Whitby and McLaws say that "such a situation should not be allowed to occur in Australia". Perhaps they need not worry about the potential cost burden in Australia. As the first customers of this new technology, US healthcare institutions, which comprise the largest medical device market in the world, are bearing the brunt of the cost burden. The new law has caused medical device companies to shift into high-volume production of safety-engineered devices. Economies of scale are already bringing prices down, as is the intense competition to gain market share in this new product area. These benefits will no doubt spill over to other countries. But I would hope for the sake of its healthcare workers, and in keeping with its strong tradition in the field of prevention, that Australia's response would be more active than simply waiting to see what washes up on shore.

Janine C Jagger MPH, PhD

Objective: To describe the frequency, cause and potential cost of prevention of hollow-bore dirty needlestick injury (NSI) sustained by healthcare workers.Design and participants: Ten-year prospective surveillance study, 1990–1999, with triennial anonymous questionnaire surveys of nursing staff.Setting: 800-bed university tertiary referral hospital in Brisbane, Australia.Main outcome measures: Rates and circumstances of NSI in medical, nursing and non-clinical staff; knowledge of NSI consequences in nurses; and minimum costs of safety devices.Results: Between 1990 and 1999, there was a significant increase (P < 0.001) in the trend of the reported rate of NSI. Of the 1836 "dirty" NSIs reported, most were sustained in nursing (66.2%) and medical (16.8%) staff, with 62.7% sustained before disposal. Hollow-bore injuries from hypodermic needles (83.3%) and winged butterfly needles (9.8%) were over-represented. Knowledge among nursing staff of some of the risks and outcomes of NSI improved over the decade. A trend (χ2 = 9.89; df = 9; P = 0.0016) with increasing rate of reported injuries in this group was detected. The estimated cost of consumables only, associated with the introduction of self-retracting safety syringes with concomitant elimination of butterfly needles, where practicable, would be about $365 000 per year. Conclusion: More than one NSI occurs for every two days of hospital operation. Introduction of self-retracting safety syringes and elimination of butterfly needles should reduce the current hollow-bore NSI by more than 70% and almost halve the total incidence of NSI.

R Michael Whitby FRACP, FRCPA · Mary-Louise McLaws MPH, PhD

Objective: To describe the natural history of rheumatic manifestations of Ross River virus (RRV) disease.Design: Prospective longitudinal clinical review.Setting: North Queensland local government areas of Cairns, Douglas, Mareeba and Atherton during January to May 1998.Participants: General practice patients diagnosed with RRV disease on the basis of symptoms and a positive RRV IgM result.Main outcome measures: Rheumatic symptoms and signs assessed as soon as possible after disease onset and on two subsequent occasions (up to 6.5 months after onset).Results: 57 patients were recruited, 47 of whom were reviewed three times (at means of 1.1, 2.4 and 3.6 months after disease onset). Results are reported for these 47: 46 (98%) complained of joint pain at first review, with the ankles, wrists, fingers, knees and metacarpophalangeal joints (II–IV) most commonly involved. Prevalence of joint pain decreased progressively on second and third reviews, both overall (92% and 68% of patients, respectively), and in the five joints most commonly affected. The prevalence of other common rheumatic symptoms and signs, and use of non-steroidal anti-inflammatory drugs, also progressively declined over the three reviews.Conclusions: Earlier studies may have overestimated the prevalence and duration of symptoms in RRV disease. Progressive resolution over 3–6 months appears usual.

David Harley PhD, FAFPHM · David Bossingham FRCP, FRACP · David M Purdie MMedSc, PhD · Nirmala Pandeya BSc, MMedSc · Adrian C Sleigh MD, MPH, FRCP

Objective: To describe the natural history, treatment and cost of Ross River virus-induced epidemic polyarthritis (RRV disease).Design: Questionnaire-based longitudinal prospective study.Participants and setting: Patients in the greater Brisbane area, Queensland, diagnosed with RRV disease by their general practitioners based on clinical symptoms and paired serological tests between November 1997 and April 1999.Main outcome measures: Scores on two validated quality-of-life questionnaires (Clinical Health Assessment Questionnaire and Medical Outcomes Study Short Form 36) were obtained soon after diagnosis and one, two, three, six and 12 months thereafter. Scores were compared between patients diagnosed with RRV disease alone and those with RRV disease plus other conditions.Results: 67 patients were enrolled. Most patients with RRV disease alone had severe acute symptoms, but followed a consistent path to recovery within three to six months. Other conditions, often chronic rheumatic diseases or depression, were identified in half the cohort; their quality-of-life scores suggested stable chronic illness between six and 12 months after diagnosis. Non-steroidal anti-inflammatory drugs (NSAIDs) were taken by 58% of patients (average use, 7.6 weeks; range, 2–22 weeks). Time off work averaged 1.9 days, and direct cost to the community was estimated as $A1018 per patient.Conclusions: Symptom duration and frequency of long-term symptoms may have been overestimated by previous studies of RRV disease. Disease persisting six to 12 months after RRV diagnosis was largely attributable to other conditions, highlighting the need to seek other diagnoses in RRV patients with persistent symptoms.

Andrea D Mylonas BA, RN · Allison M Brown RN, Grad Cert CDM · Tracy L Carthew RN, BN · David M Purdie MMedSc, PhD · Nirmala Pandeya GradDipAppSc, MMedSc · Louisa G Collins BEc, MPH · Andreas Suhrbier MA, PhD · Barry McGrath MB BS, PhD · Elizabeth J Reymond FRACGP, PhD · Philip C Vecchio FRACP, MBA · Ian D Gardner PhD, FACTM · Ferdinandus J de Looze MB BS, MSc