MERS: worst may be past

The World Health Organisation has indicated that the Middle East Respiratory Syndrome (MERS) outbreak that has so far claimed 24 lives in South Korea may have passed its peak.

While warning that it was critical health authorities closely monitor the situation, the WHO’s Emergency Committee has nonetheless declared that South Korean efforts to track and quarantine infected people had “coincided with a decline in the incidence of cases”.

Since the first case was reported in South Korea last month, 166 people in the North Asian country are confirmed to have been infected with MERS, including 30 currently receiving treatment, while a further 5930 are in quarantine at home or in medical facilities.

Fears that the disease might spread further in the region were fuelled earlier this week when Thai officials reported a visiting businessman from Oman had fallen ill with the disease, and 59 people who had been in contact with have been placed in quarantine.

But the WHO praised South Korean health authorities for rapidly alerting their Chinese counterparts about an infected traveller, who was quickly located and isolated.

The World Health Organisation’s Emergency Committee, which met earlier this week to discuss the outbreak, said it was not yet serious enough to warrant the declaration of a public health emergency, and advised that travel restrictions and airport screening were not necessary.

Nonetheless, the Committee warned the outbreak was “a wake-up call” for governments about the speed with which serious infectious diseases could spread “in a highly mobile world”.

“All countries should always be prepared for the unanticipated possibility of outbreaks of this and other serious infectious diseases,” it said. “The situation highlights the need to strengthen collaboration between health and other key sectors, such as aviation, and to enhance communication processes.”

No cases have been reported in Australia, and a Federal Health Department spokeswoman said the risk of MERS arriving in Australia was considered to be low, at least for the time being.

But health and border protection authorities are on alert for the disease, and the Federal Government is planning to warn Australians travelling overseas, particularly to the Middle East as part of the Hajj pilgrimage, about MERS and what precautions they need to take to minimise the chances of infection.

Though Korean authorities have been praised for the strength of recent actions to control the spread of MERS, serious shortcomings in their initial response have been blamed for helping the outbreak gain momentum.

The WHO Emergency Committee detailed a number of factors that helped the disease spread, including ignorance of MERS among health workers and the broader public; “suboptimal” infection prevention and control measures in hospitals; keeping patients infected with MERS in crowded emergency departments and wards for extended periods; the behaviour of patients in going to several different doctors and hospitals for treatment; and the custom of family and friends staying with their infected loved ones in hospital.

“There are still many gaps in knowledge regarding the transmission of this virus between people, including the potential role of environmental contamination, poor ventilation and other factors,” the Committee said, though adding that there was no evidence of sustained transmission in the community.

Adrian Rollins

Australia good, but can do better, on heart disease and stroke

Australia has one of the lowest mortality rates from cardiovascular disease in the developed world, but the nation has been told it needs to consider taxes on sugar-rich and unhealthy foods to combat rising obesity and diabetes.

Australia’s cardiovascular disease (CVD) mortality rate fell to 208 per 100,000 people in 2011, 30 per cent below the average among Organisation for Economic Co-operation and Development member countries of 299 per 100,000, and the potential years of life lost to circulatory diseases dipped to 372 per 100,000, 36 per cent below the OECD average of 581 per 100,000.

In a report released overnight, the OECD attributed the nation’s success in driving down deaths from heart attacks and stroke to accessible, high quality health care and effective public health policies, particularly in reducing smoking.

The Organisation said comprehensive tobacco control measures, including a hefty excise, mass media campaigns, advertising and smoking bans and, most recently, tobacco plain packaging laws, had helped drive the smoking rate down to 12.8 per cent last year, one of the lowest in the OECD and well below the average of 20.9 per cent among member countries in 2012.

But the OECD warned the nation needed to overcome several challenges if it was to cement and build upon its success in reducing CVD mortality.

It cautioned that Australia’s high obesity rate – 28.3 per cent, almost double the OECD average of 18 per cent – threatened to drive up the incidence of CVD unless it was addressed, and noted that the nation’s spending on preventive health measures had slipped to just 1.8 per cent of total health expenditure, well below the OECD average of 2.9 per cent.

In its first Budget, the Abbott Government abolished the Australian National Preventive Health Agency and absorbed its functions with the Health Department, heightening concerns of a loss of national focus and leadership on preventive health measures.

The OECD has also echoed warnings from the AMA about the dangers of deterring patients from seeing their doctor by imposing out-of-pocket costs.

AMA President Professor Brian Owler said the Government’s four-year freeze on Medicare rebates would create a patient co-payment “by stealth” by forcing doctors to reduce bulk billing and charge out-of-pocket (OOP) expenses.

The OECD said that Australian patients already faced higher than average out-of-pocket costs, and cautioned that “higher OOP costs will lead to a lower use of primary care services, particularly among the poor”.

Nonetheless, the Organisation said access to primary care in Australia was “generally good”, and the nation’s heavy use of cholesterol-lowering drugs – the highest in the OECD – showed there was ready access to medication.

The observation came two days after research was published estimating that 60,000 patients stopped taking cholesterol-lowering statins after the ABC television program Catalyst questioned their safety.

The OECD said Australians with CVD had access to good quality acute care. The 30-day case-fatality rate for acute myocardial infarction patients was 4.4 per cent, one of the lowest rates in the OECD, while case-fatality for stroke patients was around the OECD average and the proportion of stroke patients treated in dedicated facilities was higher than many other comparable countries.

The OECD said the country needed to curb the rise in obesity if it was to make further inroads into CVD fatality rates, and suggested it consider measures adopted in other countries, such as taxes on unhealthy or sugar-rich food and drinks and the development of nationally-co-ordinated health promotion programs.

Adrian Rollins

Keep GP costs down to win fight against rich world’s biggest killer, OECD says

Decades of success in cutting deaths from heart attacks and strokes are at risk unless governments ensure patients have affordable access to primary health care, the Organisation for Economic Co-operation and Development has warned, adding to pressure on the Federal Government to dump its controversial freeze on Medicare rebates.

As the AMA intensifies its campaign against the four-year freeze, which is set to drive down GP bulk billing rates and force up patient out-of-pocket costs, the OECD has said that affordable and accessible primary care is essential if the world is to build upon a 60 per cent decline in the cardiovascular disease mortality rate in the past 50 years.

In a major report on cardiovascular disease and diabetes released overnight, the OECD said although massive strides had been taken in reducing deaths from cardiovascular disease (CVD), it still remained the most common cause of death in developed countries, and rising rates of obesity and diabetes threatened to slow or even reverse these gains without a greater focus on preventive health, accessible quality primary care and more effective hospital systems.

“The prospects for reducing the CVD disease burden are diminishing, and the pattern of declining mortality is coming to an end or even reversing amongst some population groups, particularly younger age groups,” the Cardiovascular Disease and Diabetes: Policies for Better Health and Quality of Care report said. “Rising levels of obesity and diabetes are reducing our ability to make further inroads into reducing the CVD burden.”

The OECD warned that, on current trends, almost 108 million adults across the OECD would have diabetes by 2030, while an extra 23 million would have greater health needs and a higher risk of complications.

The report paid much of the credit for the decline deaths from heart attacks and strokes in recent decades to public health campaigns, particularly on smoking.

All OECD countries have taken anti-tobacco measures including mass media campaigns, higher taxes, advertising bans and quit services, with the result that between 1997 and 2009 the proportion of adults lighting up daily fell from 28 to 20 per cent.

“Smoking policies have been shown to be highly effective. Tobacco control policies…have saved lives,” the OECD said.

It said that although evidence about the effectiveness of Australia’s world-leading tobacco plain packaging laws was still being gathered, the initiative “may provide the next set of policy instruments for governments to help further reduce the harmful impact of smoking”.

But governments have so far been much less successful in curbing rates of obesity and diabetes, which the OECD said would instead revolve around the strength of a country’s primary health care system.

“Primary care is the centre of the health care system, and is particularly so for CVD and diabetes,” it said, emphasising the importance of affordable and accessible quality care.

“A highly accessible primary care system has the capacity to reduce inequalities in health outcomes and deliver care to those who stand to benefit most,” the report said. “This is particularly important for diseases such as diabetes, which is far more prevalent among lower socio-economic groups.”

It is a timely warning as the AMA ramps up its campaign against the Federal Government’s plan to freeze Medicare rebates until mid-2018.

AMA President Professor Brian Owler has criticised the policy as a “co-payment by stealth” because rising practice costs will force many GPs to dump bulk billing and charge their patients out-of-pocket fees.

Professor Owler said this was concerning because it raised the risk that patients would put off seeing their GP until their health problem became so serious it required hospitalisation.

It is a concern shared by the OECD, which warned that how primary care was funded had “enormous implications” for access to care and health.

“Higher out-of-pocket costs will lead to a lower use of primary care services, particularly among the poor,” it said. “By foregoing routine visits…patients are exposed to greater risk leading to a worsening of health status.

“It is therefore essential that primary care remains highly accessible to all.

“Good access is a necessary requirement to enable primary care practitioners to have regular contacts with patients, assess patient risk, monitor progress, deliver care and adjust treatments when required.”

As part of its report, the OECD examined ways to improve the quality of primary and acute care, including using digital technology to share up-to-date patient information and monitoring their health, as well as pay-for-performance schemes, better hospital access and public reports on the relative performance of hospitals and other health services.

It found that although there was some evidence that pay-for-performance schemes, under which doctors are paid for outcomes – usually in chronic and preventive care – can achieve some improvements, this is often highly contingent on a range of other conditions being in place, meaning great care had to be exercised in implementing such a payment model.

While lauding the success of recent decades in curbing CVD mortality rates, the OECD nonetheless said that it remained the “number one killer” in most member countries, and there were concerns about riding rates of obesity and diabetes, and gaps between recommended health care and that which was actually provided.

The Organisation said it was not just a matter of more money.

“The evidence on what constitutes good quality care has been I the public domain for decades, but many OECD countries are still coming to terms with the changes that need to be made in their health systems to deliver such care,” it said.

The OECD said that one of the most significant challenges was to take evidence about best treatment and make it part of everyday practice.

Adrian Rollins

Australia ‘a climate change laggard’

The Federal Government needs to take “much more” action on climate change if the nation is to mitigate its most harmful effects on human health, AMA President Associate Professor Brian Owler has warned.

In an address to the AMA National Conference, A/Professor Owler defended the AMA’s advocacy on climate change against critics who claimed the issue lay outside the Association’s realm of expertise.

The AMA President said that although medical practitioners did not have expertise in climate science, they were well placed to comment on the likely health effects of climate change, which included the likely spread of mosquito-borne diseases into formerly temperate areas, increased deaths from heatwaves, storms and other extreme weather, and the health impact of changes in nutrition as farming patterns are disrupted.

“Our perspective is to come at climate change from the health perspective,” he said. “The best scientific evidence is that there is going to be climate change and there will be health consequences.”

Earlier this year, the AMA helped launch and Australian Academy of Science report on the health effects of climate change, and A/Professor Owler said that, just as doctors followed the scientific evidence on the efficacy of vaccinations, so they also followed the evidence on changes to the world’s climate.

He said that, while the issue had become heavily politicised, the overwhelming weight of evidence showed that it was occurring and “the vast majority of AMA members understand the importance that we mitigate against climate change and its potential health impacts”.

“There is overwhelming support at [the AMA] National Conference for the AMA to speak out on this issue,” A/Professor Owler said. “The health effects can be quite far reaching, and what we don’t want to see is people ignoring climate change.”

The Federal Government is coming under mounting pressure to take more action on climate change ahead of the next round of United Nations talks in Paris in November.

The AMA’s call for more work to mitigate its health effects have been echoed by the World Medical Association, which late last month called for the issue to be given a higher priority at the Paris talks.

WMA President Dr Xavier Deau said he was very concerned that crucial health issues were being ignored in the build up to the Paris meeting, and that time was running out for the voice of the health community to be heard.

The call came as a leading British think tank singled out Australia as a “climate change laggard” among the world’s developed countries.

The UK-based Grantham Institute on Climate Change and Environment reported that Australia was the only developed country to “take a legislative step backwards” from action on climate change.

A/Professor Owler said the Government’s approach to climate change was going to be very important in the lead-up to the Paris summit, “but so far the Government’s response has been disappointing. We want to see more action on climate change”.

Adrian Rollins

Knowing when to stop antibiotic therapy

In reply: Thompson and colleagues make an important point: contradicting dogma about the need to complete an antibiotic course is risky and potentially confusing.

My article1 was not written for patients, but it attracted media interest and public comment.2,3 I did not suggest that patients stop taking antibiotics as soon as they feel better, as some assumed2 — although I suspect many do.

Clearly whether they can do so safely, depends on the indication. It would be reasonable for a patient to ask, if the doctor has not explained, whether completing the course is necessary. If, as I suspect is still common, the antibiotic was prescribed for an acute respiratory infection, it is certainly sensible to stop when symptoms improve — albeit better not to have started.

Even when there is a good indication for taking antibiotics, pack sizes often do not correspond with recommended course durations,4 and both are often based on limited evidence. Shorter courses are likely to be just as effective for many infections.5 We need more evidence and more common sense, because unnecessary or unnecessarily long antibiotic courses promote resistance.6

BCG for the prevention of food allergy — exploring a new use for an old vaccine

BCG has profound immunomodulatory effects that may reduce the risk of food allergy in children

The prevalence of allergic disease in developed countries has risen dramatically since the mid 20th century and Australia now has the highest documented prevalence of childhood food allergy in the world.1 Theories to explain this rise include changes in the timing of food introduction, epigenetic changes related to environmental factors, and alterations in micronutrient status (particularly of vitamin D). Interactions between the human microbiome, microbial exposures during infancy and the developing immune system are particularly important. According to this model, termed the “hygiene hypothesis” or, more recently, “biome depletion”,2 immune system development may be influenced not only by infections, but also by exposures to animals and antibiotics, and through birth by Caesarean section.

There are currently no interventions to combat the epidemic of food allergy. However, vaccination with live attenuated Mycobacterium bovis, also called bacille Calmette-Guérin (BCG), might offer a strategy to reduce the risk of allergic disease at the population level or in high-risk groups. Administered shortly after birth to protect against tuberculosis, BCG is the oldest vaccine still in routine use (since 1921), and is one of the most widely used vaccines in newborns and young infants worldwide. It has a long-established safety profile: with correct intradermal administration, local adverse effects occur in fewer than 1% of vaccinees. Disseminated BCG disease is rare, usually occurring only in the context of HIV infection or rare inherited immunodeficiencies. The ability of BCG to influence the immune response to diseases unrelated to tuberculosis has become a topic of great interest with broad, global implications.3 It is these immunomodulatory effects, distinct from the protection it provides against tuberculosis, that underlie the possibility that BCG might be useful in reducing the risk of allergic disease.

T-helper cells, atopy and heterologous immunity

For more than half a century, it has been recognised that natural infections can affect the immune response to unrelated pathogens by, for example, altering the balance in T-helper cells. T-helper 1 (Th1) and T-helper 2 (Th2) cells are subsets of adaptive T-lymphocytes that are distinguished on the basis of the cytokines they produce. In simple terms, Th1-mediated responses are associated with protection against intracellular pathogens (and also some autoimmune diseases), while Th2-mediated responses are linked to IgE production, atopy (elevated sensitivity to certain allergens), and protection against extracellular parasites. A balance between these two cell types is maintained by reciprocal inhibition and through regulation by T-helper 17 and regulatory T-cells.

Recent evidence suggests that BCG vaccination can alter T-helper cell polarisation in a similar manner to natural infection.4 In particular, after a natural infection or BCG vaccination, T-cells can cross-protect against other, unrelated pathogens in a process known as heterologous T-cell immunity.3,5 Further, the innate immune system, like the adaptive immune system, has the ability to learn from past experience in a phenomenon termed “trained immunity”.6 BCG vaccination enhances or trains the innate immune response to subsequent infection through epigenetic reprogramming of monocytes.5

It has been proposed that these immunological mechanisms explain the remarkable finding that, in high-mortality settings, certain infant vaccinations have an effect on child mortality that is not explained by their effect on the targeted disease (the concept of heterologous or non-specific effects of vaccines).3,7 There is evidence that live attenuated vaccines, such as BCG and the measles vaccine, reduce all-cause infant mortality in high-mortality settings, primarily by protecting against neonatal sepsis and respiratory infections caused by pathogens other than Mycobacterium tuberculosis and the measles virus.3,7 Further, recent evidence from Denmark suggests that the measles–mumps–rubella (MMR) vaccine reduces the risk of hospitalisation for infectious diseases caused by unrelated (non-targeted) pathogens for at least 6 months after vaccination,8 showing that there is also a direct relevance to high-income, low-mortality settings such as Australia.

The impact of childhood vaccinations on heterologous immunological development raises the question of whether other immune-mediated conditions might be affected by childhood vaccinations. Atopic disease is characterised by dysregulation of the immune system, particularly by Th2 cell polarisation, partly due to epigenetic changes related to exposure during early life to microorganisms, micronutrients and other modulators of the immune system.9

The first randomised trials of BCG in at-risk infants

Food allergy, in particular, is one of the earliest manifestations of the atopic phenotype and has been described as the “second wave” of the allergy epidemic.9 Its prevalence is rising at a time when the prevalence of other atopic diseases has plateaued, and it now affects about 10% of 12-month-old infants in Melbourne.1 As Th2 cell polarisation in these cases probably occurs very early in infancy, possibly in utero, neonatal BCG vaccination could potentially divert immune system development toward a less atopic phenotype and prevent subsequent clinical food allergy because of its marked Th1 cell polarising effect. Importantly, BCG is suitable for administration immediately after birth.4

Recent reviews suggest that vaccination with BCG protects against childhood asthma and eczema, but there have been few randomised controlled trials and the data from observational studies are inconsistent.10,11

Although the two randomised trials of BCG and atopic disease that have been reported had shortcomings, and neither was designed to specifically investigate food allergy, their results are nevertheless interesting. In the first study, 121 6-week-old infants at high risk of allergic disease (having a close relative with allergic disease) in the Netherlands were randomised to vaccination with BCG or placebo to determine whether BCG vaccination reduced the rate of subsequent allergic disease. At 18 months of age, BCG vaccination was associated with reduced prevalence of eczema (relative risk [RR], 0.72; 95% CI, 0.5–1.0; P = 0.07) and reduced use of eczema medication (RR, 0.58; 95% CI, 0.3–1.0; P = 0.04), but there was no effect on other allergic diseases.12 However, the study was stopped well before the target number of infants had been enrolled, so that it was underpowered and unable to definitively determine whether BCG vaccination had an overall effect on atopic disease. Further, infants were vaccinated at 6 weeks of age, but there is evidence that the protective effects against atopic sensitisation are greatest when BCG is given during the first week of life.13

The second randomised trial compared early (median age: 2 days) versus late (median age: 42 days) BCG vaccination in 281 low-birthweight infants in Guinea-Bissau, West Africa.There was no overall effect on atopic sensitisation (assessed by skin-prick testing) 3 to 9 years later. However, when children who had been given a vitamin A supplement (a potential effect modifier) were excluded from the analysis, early BCG appeared to have been protective (odds ratio [OR], 0.40; 95% CI, 0.15–1.06; P = 0.07). Interestingly, among all children, those who had responded to BCG vaccination by developing a scar had a diminished risk of sensitisation (OR, 0.42; 95% CI, 0.19–0.94; P = 0.03). However, the small size of the study made it impossible to determine a general effect of BCG vaccination on atopic sensitisation. The study was also limited by the absence of an unvaccinated control group. Finally, the high burden of infectious disease in the treated population and the low prevalence of atopic disease in Africa limit its relevance to children in Australia.13

The next steps

Neither of these studies investigated food allergy adequately, but definitive trials are underway elsewhere. In Melbourne, more than 1400 infants are being enrolled in a randomised controlled trial to investigate whether BCG at birth reduces allergy and infection during the first year of life (ClinicalTrials.gov identifier: NCT01906853). Extensive immunological studies as well as investigation of the gut and respiratory microbiome will help unravel the mechanisms underlying any observed effects.14 In Denmark, 4300 infants have been enrolled in a randomised controlled trial of BCG vaccination at birth, with the primary outcome being hospitalisations by 15 months of age (ClinicalTrials.gov identifier: NCT01694108). Secondary outcomes include allergic disease in general and food allergy in particular; immunological studies will complement the epidemiological investigation.15 Each study also includes the prevalence of non-tuberculosis infectious diseases as outcomes, based on the ability of BCG to confer protection against unrelated infections.

The World Health Organization has recently highlighted the potential importance of the heterologous effects of BCG vaccination and advocated that more studies be undertaken to identify the underlying immunological mechanisms.16 In addition to BCG, the possible heterologous effects of other vaccinations need further exploration, both in relation to doses and timing.13 If routine childhood vaccinations in younger infants leave profound, long-lasting impressions on the immune system that influence susceptibility to non-targeted infections,7,17,18 it is not inconceivable that other immune-mediated diseases, including food allergy and other atopic diseases, may also be affected. The possibility of using currently available vaccinations to alter the immune system in this beneficial manner is an exciting prospect in the battle against the epidemic of allergic disease.

Consensus guidelines for the investigation and management of encephalitis

A summary of a position paper for Australian and New Zealand practitioners

Encephalitis is caused by inflammation of the brain and is a challenging condition for clinicians to identify and manage. It manifests as a complex neurological syndrome with protean clinical manifestations that may be caused by a large number of aetiologies, many without effective treatments. It can be fatal and survivors often experience significant neurological morbidity. Studies have shown variable quality in case management in multiple settings,1–3 emphasising the need for consensus guidelines.

The need for guidelines is also important because encephalitis is a marker of emerging and re-emerging infectious diseases, and is therefore a syndrome of public health importance. There are unique infectious aetiologies in Australia — including Hendra virus, Australian bat lyssavirus, Murray Valley encephalitis virus and West Nile virus (Kunjin virus) infections — that require early identification, reporting and specialist clinical and public health responses. Regionally, causes of encephalitis with potential for introduction into and epidemic activity in Australia include Japanese encephalitis virus, enterovirus 71, dengue virus and Nipah virus. There is also a rapidly growing list of immune-mediated encephalitides that are important because of their potential response to immunomodulatory treatments and their association with underlying tumours.

“encephalitis is a marker of emerging
and re-emerging infectious diseases”

Although comprehensive guidelines have been published elsewhere, including recent international consensus guidelines,4 these are detailed and lack a specific geographic focus. As a result, we have developed a concise guideline for clinicians in Australia and New Zealand5 (doi: 10.1111/imj.12749) that provides a substantial update to previous guidance published in the Journal.6

The guideline was developed by the Australasian Society for Infectious Diseases Clinical Research Network (ASID CRN) Encephalitis Special Interest Group with subsequent, multiple rounds of consultation involving the ASID Guidelines Committee, the Public Health Association of Australia, the Australian and New Zealand Association of Neurologists and the Australasian College for Emergency Medicine.

Main recommendations

The guideline principally consists of two algorithms. The first algorithm addresses the patient with possible meningoencephalitis — a scenario that is frequently encountered in emergency departments. This algorithm is designed to assist clinicians to: consider encephalitis within a wide differential diagnosis, perform appropriate specimen sampling and investigations, and initiate antimicrobial therapy promptly (including acyclovir for possible herpes simplex virus [HSV] encephalitis). In most patients with possible meningoencephalitis, an alternative diagnosis will be made. The algorithm aims to discriminate between patients in whom encephalitis can be excluded and those who require a more detailed assessment. The second algorithm addresses the patient in whom encephalitis is considered likely. This algorithm provides a robust clinical case definition of encephalitis, identifies key first-line (universal) diagnostic tests (Box), outlines a process of excluding HSV disease, and formulates an approach of directed (second- and third-line) diagnostic testing based on risk factors, clinical features and radiological features.

In addressing these scenarios, the guideline answers the following questions:

What features are important to consider during history-taking and examination?
In which patients should magnetic resonance imaging be performed?
What are the common abnormalities evident in cerebrospinal fluid?

Furthermore, it provides advice on the tests that should be done to diagnose the most common causes of encephalitis and defines specific patient subpopulations to highlight differences in aetiology (to help prioritise testing). These subpopulations include: children and neonates, immunocompromised patients, overseas travellers and immigrants, and patients residing in tropical Australia.

The guideline considers the particularly vexing question of the contemporary role of brain biopsy by presenting evidence of its yield in cohorts of patients who have encephalitis. It also introduces the various immune-mediated encephalitides, describes their clinical features and, in doing so, assists the clinician in deciding when to perform specific antibody studies. From a treatment perspective, the guideline defines optimal therapy for HSV encephalitis and outlines possible treatment strategies for other infectious and immune-mediated causes based on lower-quality evidence. In particular, it suggests when to consider empiric antimicrobial therapy and immunomodulatory therapies.

Encephalitis presents a complex challenge to clinicians. Its possibility must be suspected in a variety of presentations, and it requires the performance of a detailed clinical assessment, consultation, and judicious investigation. Unnecessary delays must be avoided, and it is essential to institute empiric therapies appropriately and provide high-quality supportive management. Optimal application of current knowledge is likely to improve diagnosis; however, even with an extensive diagnostic work-up, definitive aetiology may not be identified for 30%–40% of patients with encephalitis.7 Novel agents and a changing geographical distribution of known diseases are likely to be identified with improved surveillance; these possibilities should be considered where unexplained encephalitis clusters occur.

Box anchor (office use only)

Recommended first-line investigation of encephalitis in Australia and New Zealand*5

* Table reproduced with permission from: Britton PN, Eastwood K, Paterson B, et al; Australasian Society of Infectious Diseases; Australasian College of Emergency Medicine; Australian and New Zealand Association of Neurologists; Public Health Association of Australia. Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand (Internal Medicine Journal, Wiley Publishing Asia Pty Ltd, © Royal Australasian College of Physicians 2015).

[Case Report] Hypoplastic left heart in the 6500-year-old Detmold Child

Palaeopathology, the scientific study of ancient diseases, has evolved in recent decades into a modern scientific area and become part of medical research. Virtual autopsies, like those undertaken in modern forensic institutes, can be done on ancient mummies to examine injuries, genetic defects, acquired diseases, and determine sex.1

Potential public health benefits of HIV testing occurring at home in Australia

In Australia between 1999 and 2013 the annual number of HIV diagnoses rose by over 70%, from 724 to 1236, and gay and bisexual men (GBM) accounted for 70% of new cases.1 HIV testing is recognised in the Seventh National HIV Strategy as a key public health strategy.2 Increased HIV testing leads to earlier detection of HIV infections, which allows people who are diagnosed to reduce the risk of transmission to others by modifying their sexual practices.3 Being diagnosed with HIV also allows people to decide whether they wish to initiate treatment that suppresses viral replication and thereby reduces infectiousness.4 Mathematical modelling has predicted that substantial increases in HIV testing can reduce HIV incidence in the community.5

Despite GBM having access to laboratory HIV testing through clinical services, HIV testing rates remain less than ideal. Less than a quarter of high-risk GBM undergo testing at the recommended frequency (3–6 monthly).6 Surveys show the proportion of GBM who have never had a test for HIV is 14%–26%,7,8 and in 2013 there were about 3700 people undiagnosed and living with HIV in Australia.1 GBM consistently report structural barriers to HIV testing,9,10 and 61%–67% report they would undergo testing more frequently if home testing were available.11,12

In an effort to increase testing rates in Australia, legislation regulating the availability of in vitro devices was recently modified to allow the Therapeutic Goods Administration to consider applications for licensing of HIV self-tests. Policies have also been changed to support HIV self-testing in other countries, including the United States, United Kingdom, France and Kenya. In the US, the oral fluid OraQuick In-Home HIV Test (OraSure) has been approved by the US Food and Drug Administration (FDA) and is commercially available. Studies in untrained users show the sensitivity of the OraQuick self-test to be 91.67%, but the specificity is nearly 100%,13 which means very few false-reactive results occur.

Despite the lower sensitivity of the OraQuick self-test compared with laboratory tests, the approval by the US FDA was based on public health grounds. A mathematical model was developed which assumed that 2.8 million people in the US (seropositivity of 1.6%) would use the self-test in its first year of use. Based on the known sensitivity of the self-test, this would yield 45 000 positive test results and 3800 false-negative results. The model predicted that, by uncovering this large number of previously undiagnosed infections, the self-test might avert more than 4000 new HIV transmissions during the first year.14

Australia’s HIV epidemic is quite different to that in the US, with a higher proportion of new infections among GBM.1 Our health system also differs, with more widely available highly sensitive fourth-generation laboratory HIV immunoassays (IAs) and easily accessible inexpensive primary health care. Therefore, it is important to confirm that there would be public health benefits of HIV self-testing before introducing it in Australia. We assessed the potential benefit to public health of HIV self-testing in Australia, defined by the number of HIV infections detected that otherwise would have remained undiagnosed.

Details of our analysis

We prepared a series of calculations to assess the chance of detecting HIV among Australian GBM at high risk of infection if the OraQuick self-test were used, compared with a laboratory fourth-generation IA. We also assessed what level of HIV testing frequency is required for the number of new HIV infections detected by HIV self-tests to offset any infections missed due to the lower sensitivity of the self-test. We applied these calculations to a range of testing scenarios.

Population studied

Our analysis focused on men who reported higher behavioural risk, among whom HIV incidence levels are greatest.15 Such men also report a greater willingness to use HIV self-tests.11 High risk was defined as reporting more than ten sexual partners in the past 6 months, and/or any unprotected anal intercourse with casual partners, and/or unprotected sex with an HIV-positive partner. For this high-risk population, we applied an HIV incidence of 2.4 per 100 person-years overall and 6.4 per 100 person-years in untested men (Box 1).15

Our assumptions regarding test performance

Based on data from the OraSure clinical trial conducted with participants who had not been trained in how to use the test,13 we assumed that the self-test, which detects only antibodies in oral secretions, has an overall sensitivity of 91.67%. We also assumed that the window period was 25–35 days (median 30 days).18 We assumed that the fourth-generation IA, which detects p24 antigen (ie, part of the virus) as well as antibody in blood, has a sensitivity of 99.94%19 and a window period of 15–20 days (median 17.5 days) (Box 2).18

Calculating the chance of HIV detection

We calculated the proportion of infections that would remain undiagnosed if the self-test replaced a single fourth-generation IA laboratory test at an individual level.

We then calculated the chance of HIV detection via test frequencies of a single yearly test, two or more tests in a year, every 1–2 years, and greater than 2 years ago (Box 3). The chance of HIV detection for both the self-test and fourth-generation IA was also assessed (Box 3). We assumed that test sensitivity is the probability of detecting a true positive and that an infection would occur on average at the midpoint between the last true-negative test and the next HIV test.

Calculating the proportion of infections that would go undetected if the OraQuick HIV self-test replaced fourth-generation IA

Based on the usual testing frequency among high-risk GBM, we calculated the proportion of infections that would go undetected per year if self-tests replaced IA tests. We calculated the weighted average across the proportions of men who test a given number of times per year, n, and the probability of not detecting an established infection, using the following equations:

Probability(missing an infection with IA | average of one test per year) = (1 − 0.9994)1

Probability(missing an infection with self-test | average of X tests per year) = (1 − 0.9167)X

(where “|” indicates conditional probability; ie, the probability of event A given that event B occurred).

Then, to determine what level of HIV testing frequency is required for the number of new HIV infections detected by HIV self-tests to offset any infections missed by the lower sensitivity of the self-test, we used this calculation:

X = 1*log(1 − 0.9994)/log(1 − 0.9167)

We assumed that high-risk GBM had on average one test per year, based on clinical data that showed an average testing frequency of around 1.5 tests per year among men who presented to a clinic for testing;20 but, as 27% of men do not attend a clinic for testing in a year, we reduced it to one test per year on average.

Outcomes of our calculations

The net benefit of replacing fourth-generation laboratory IA tests with HIV self-tests depends on the frequency of testing in the target population.

If a group of high-risk GBM were going to receive a single fourth-generation IA test, but instead undertook a self-test, then about 8% of the infections that would have been diagnosed by the IA test would remain undetected due to the lower sensitivity of the self-test.

If self-testing increased across all GBM at high risk so that men had three self-tests per year on average, compared with one conventional fourth-generation IA, then zero infections would be missed. If four self-tests occurred, additional infections would be detected (ie, meeting our definition of public health benefit).

Additional infections would also be detected for any extra self-test which was supplementary to usual fourth-generation laboratory IA testing. Self-testing could have a large benefit among men who would otherwise remain untested. For example, among 10 000 untested GBM, with an incidence of 6.4 per 100 person-years,15 640 new infections would occur. Use of a single self-test by these men would detect about 586 infections that would otherwise go undetected.

Discussion

Results of our calculations show that HIV self-testing would have a public health benefit if access to the self-test led to Australian GBM at high risk of infection supplementing their conventional testing with self-tests. If self-testing resulted in untested GBM having an HIV test for the first time, there would also be a public health benefit (even a test with lower sensitivity is better than no test). A good uptake of self-testing seems plausible, considering the interest expressed in surveys.11,12 The uptake of self-tests as supplemental testing or by previously untested men would reduce the average period of undiagnosed infection. The approximately 9% of undiagnosed HIV infections among Australian GBM disproportionately account for a third of new HIV infections.21 Mathematical modelling suggests that reducing the time between infection and diagnosis can lead to reductions in population incidence.22

If the availability of self-tests resulted in GBM replacing their conventional laboratory test with self-tests, then men would need to undertake three or more self-tests a year to counteract the lower sensitivity of the self-test. Conducting three self-tests a year is consistent with clinical guidelines, but there would need to be systems to facilitate this, such as online ordering and subsidised tests from pharmacies via repeat prescription. If replacement occurred but only two self-tests were undertaken, then HIV infections would be missed. This suggests that if self-testing is introduced, men who are already linked with care would need to be encouraged to continue their annual sexual health check-ups. Recent qualitative research found that most GBM would supplement but not replace conventional blood testing with self-tests, because they valued screening for other sexually transmitted infections and the professional expertise and support provided at health services.23

Other considerations for introducing self-tests include cost. GBM in Australia report they would be unwilling to pay more than $30 for self-tests, preferably less than $20;24 however, in the US a self-test currently costs around US$40. This cost still compares favourably to clinic visits, where there are often clinic fees, patient travel costs, clinical staff salaries, infrastructure and pathology costs. Lower rates of linkage to care, and psychological distress after a receiving a reactive self-test result have been raised as potential risks. However, in the US, the OraSure Unobserved Use Study found most people (96%) identified as HIV-positive reported they intended to seek medical care.25 Self-tests kits should have clear instructions about seeking medical care and available support lines.

There are some points to consider when interpreting our results. First, the calculations conducted were simple but provide some examples of the likely benefit of high-risk GBM having access to self-tests. We have provided a rough estimate of the level of change required in practice to offset reductions in sensitivity if replacement were to occur. We realise that it is likely that not all high-risk GBM would use HIV self-tests. Surveys show that about 61%–67% of GBM would undergo testing more frequently if HIV self-tests were available.11,12 Our calculations are relevant to the subgroup of GBM who would consider using HIV self-tests.

In October 2013, the first Australian randomised controlled trial of OraQuick oral self-tests in high-risk GBM commenced (called FORTH), which includes two target groups of high-risk GBM; those who test infrequently (last test > 2 years ago) and test more frequently (past 2 years).26 FORTH will provide more accurate information on the actual HIV testing frequency that can be achieved with HIV self-testing and the extent of supplementing versus replacement of conventional tests. Mathematical modelling will be conducted using these estimates.

In conclusion, these calculations suggest that HIV self-testing should be made available to Australian GBM, provided it leads to increased testing among: GBM who have not undergone testing before; men supplementing their conventional testing with home testing; or men replacing their usual conventional testing frequency with four self-tests a year. HIV infections have increased by over 70% in the past 15 years,1 and innovative methods are needed to increase testing and treatment to sufficient levels in order to control the HIV epidemic.

1 Parameters for calculations

General practitioner management of notifiable diseases is central to communicable disease control

To the Editor: Public health units routinely carry out investigations into cases of notifiable diseases, specified by state and territory Public Health Acts, because of the potential impact on the health of the public. Investigations involve contacting individuals and their contacts, and providing advice for follow up and treatment. This may include seeing a general practitioner for further testing, treatment, or prophylaxis of contacts.1 To assess the extent of input from GPs in managing notifiable diseases we documented GP encounters related to public health unit communicable disease control activity in inner-western and south-western Sydney.

Data on routine communicable disease activity in Sydney and Sydney South West Local Health Districts were collected over 2 months from 1 June to 31 July 2014. For all investigations into suspected and confirmed cases of notifiable disease, data were collected on the type of condition, visits to GPs and tests specifically requested as part of routine public health follow-up. The study was approved by Sydney Local Health District Ethics Review Committee. There were 220 investigations associated with suspected or confirmed cases of 34 notifiable conditions during the study period, requiring 212 GP visits and 286 tests. The Box lists conditions according to their required level of GP input (those involving GP encounters more than 50% of the time were considered to require high-level GP input). Influenza and gastroenteritis outbreaks, typhoid, rubella, hepatitis E and measles were the conditions requiring the highest level of GP input per investigation. Measles, arbovirus, pertussis and gastroenteritis outbreaks were conditions with the highest frequency of suspected or confirmed cases that also required high-level GP input. Based on population size, we estimated that, if extrapolated to state level, communicable disease control activities would have resulted in about 1047 GP visits across New South Wales in the same time period.

Our findings indicate that GP encounters are central to communicable disease control and shed light on which conditions require the most input from GPs. Influenza outbreaks, measles and gastroenteritis outbreaks are of particular concern. Influenza outbreaks require particularly high-intensity input from GPs, while measles and gastroenteritis outbreaks are frequently investigated conditions that require high-level GP input. Influenza and measles are serious conditions, often involving vulnerable populations (nursing home residents and children).2,3 Our results indicate that primary care plays an important role in protecting the public from conditions with potentially serious consequences. This finding should be considered in policy discussions about access to primary care.

Visits to general practitioners and tests associated with communicable disease investigations

Condition or infection investigated (suspected and confirmed cases)	No. of investigations	Average no. of visits per investigation	Average no. of tests per investigation

High-level GP input
Influenza outbreak*	5	14.8	20.2
Typhoid	1	9.0	17.0
Gastroenteritis outbreak†	17	2.1	3.7
Rubella	2	1.5	1.0
Hepatitis E	8	1.4	1.4
Measles	24	1.0	1.6
Varicella	1	1.0	1.0
Arbovirus	19	0.9	0.8
Pertussis	18	0.9	0.7
Legionella	9	0.8	0.9
Intermittent GP input
Hepatitis A	4	0.5	0.5
Q fever	2	0.5	1.0
MERS Co-V	2	0.5	1.0
Hepatitis B	7	0.4	0.4
Malaria	3	0.3	0.3
Shigella	11	0.2	0.3
< 16 Chlamydia‡	6	0.2	0.0
Salmonella	9	0.1	0.1
Cryptosporidiosis	11	0.1	0.0
No GP input
Rotavirus	5	0.0	0.0
Mumps	5	0.0	0.2
Meningococcal	7	0.0	0.0
Lymphogranuloma venereum	1	0.0	0.0
Invasive pneumoccocal disease	22	0.0	0.0
Hepatitis D	3	0.0	0.0
Hepatitis C	2	0.0	0.0
Haemophilis influenzae B	1	0.0	0.0
Diphtheria	4	0.0	0.5
Creutzfeldt–Jacob disease	1	0.0	0.0
Brucellosis	2	0.0	0.0
< 16 Gonorrhoea‡	1	0.0	0.0

MERS Co V = Middle East Respiratory syndrome (MERS) coronavirus. * Three or more epidemiologically linked cases of Influenza-like Illness in residents or staff of child care or aged care facilities within 72 hours PLUS at least one case with a positive laboratory test result OR at least two cases with a positive point-of-care test. † Two or more cases of vomiting or diarrhoea in an institution are followed up as a possible outbreak. ‡ Conditions followed up in children aged under 16 years only to ensure they are not at risk.

	Chance of detection*
	Tested > 2 years ago	Tested every 1–2 years	Testing frequency in past 12 months

Assay			1	2	3–4	≥ 5

Fourth-generation immunoassay	99.94%	99.94%	99.94%	99.97%	99.98%	99.99%
OraSure OraQuick self-test	91.67%	91.67%	91.67%	95.49%	96.97%	98.49%

* For the purpose of calculation, we assumed the test sensitivity is the probability of detecting a true positive and assuming that an infection would occur on average at the midpoint between the last true negative test and the next HIV test. For the purpose of calculations, we assumed three tests were conducted for the category of 3–4 tests in the last 12 months, and six tests were conducted for the category of ≥ 5 tests in the last 12 months.