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Preference: Infectious Diseases and Parasitology

434

Tick-borne infectious diseases in Australia

The incidence of tick-related medical problems in Australia is largely unknown. Appropriate diagnostic tests are not always available and, of all tick-related diseases, only Q fever is notifiable.1 Anecdotally, however, many patients present to their doctor after a tick bite. This narrative review focuses on tick-borne infections but also touches briefly on other medical problems caused by tick bites.

Australian ticks

There are many different species of ticks in Australia. Only a few species are known to bite humans, and the microbes within these particular ticks — viruses, bacteria or protozoa — are potential causes of infection in humans who are bitten (Box).

However, the mere detection of a potential human pathogen in a tick does not mean that it can be transmitted to a person when bitten. To be transmitted to a person, the microbe must be present in the salivary glands of the tick while it is feeding.

Most studies of Australian ticks to date have investigated the whole microbiome of the tick and not their salivary glands specifically. Some pathogens may be present in the tick faeces, but transmission would require the patient to scratch the faeces into their skin — an unlikely scenario in most cases.

To be confident that a microbe in a tick is responsible for a particular illness in a patient bitten by that tick, it is essential to also detect the microbe in the sick patient, either directly by culture or detection of microbial nucleic acid or antigen, or indirectly by detecting newly produced antibodies to the microbe in the patient’s blood. This requires the diagnostic laboratory to have assays that are both sensitive and specific for detecting the microbe in question. Few such assays are currently available in Australian diagnostic laboratories. Antibody assays are designed using antigens from a specific microbe and in many cases these microbes are not present in Australia. Such assays, even if reasonably sensitive and specific, must have acceptable positive and negative predictive values in Australia, so that patients and their doctors can have confidence in either a positive or negative result from any particular laboratory assay.

There have been two major studies of Australian ticks,2,3 which defined their variety and number. Australian ticks are divided into two large groups: soft-bodied and hard-bodied, comprising 14 and 56 species respectively.4 Five species of ticks have been introduced into Australia,4 but most are not important in biting humans. Of the endemic species, which are the majority, two are notorious for biting humans. On the east coast of Australia, the paralysis tick (Ixodes holocyclus) is the most notable; elsewhere in Australia, it is the ornate kangaroo tick (Amblyomma triguttatum). Both ticks are known to sometimes transmit human pathogens to people when they bite. The southern reptile tick (Bothriocroton hydrosauri) also bites humans and transmits infection (Box).3

There are four stages in the life history of ticks: egg, larva, nymph and adult (male and female). The larva, nymph and adult female (egg-producing) stages require a blood meal from a vertebrate animal to metamorphose into the next life stage. The stages that most often cause problems to humans are nymphs and adult females.

Most people are bitten by ticks without any problem arising from this abnormal host–ectoparasite feeding interaction. Humans are incidental hosts and attached ticks are usually detected by the individual within a few hours, or a day at the most, and killed. Most are probably not even aware when they are bitten by a tick, as the tick injects a local anaesthetic into the skin. However, once it starts to feed, it becomes noticeable as it enlarges.

The range of problems that may occur after tick bites can be classified as follows: infection; allergy; paralysis; autoimmunity; post-infection fatigue; and Australian multisystem disorder.

Viral infections

Although there are several viral infections associated with ticks in other parts of the world (eg, tick-borne encephalitis virus in Europe), there are no definite tick-borne viral infections of humans yet discovered in Australia. The seabird soft tick (Ornithodoros capensis) has been shown to contain several viruses including the Saumarez Reef virus.5 When this tick bites humans, a dermatological condition develops in some patients, but it is not yet clear whether this is due to a virus or an allergen in the tick saliva. A phlebovirus present in an Australian bird tick (I. eudyptidis) is pathogenic for the shy albatross6,7 and is closely related to the human pathogenic viruses that cause severe fever with thrombocytopenia syndrome and Heartland virus disease. This suggests that human pathogenic viruses may be present in Australian ticks, although there is currently no evidence of I. eudyptidis biting humans.

Bacterial infections

Many different bacteria have been detected in Australian tick species,8–13 mostly using molecular techniques. Some are known human pathogens or are closely related phylogenetically to known human pathogens; others are unique bacteria that are part of the tick microbiome.

Apart from the occasional local bacterial infection at the tick bite site (eschar), there are only two definite, known systemic infections following tick bites in Australia — rickettsial infection and Q fever — although there are other possible microbial pathogens and possibly as yet unknown infections (Box).

The two genera of bacteria currently confirmed as Australian tick-transmitted human pathogens are rickettsial species and Coxiella burnetii.

Rickettsial species

In Australia, rickettsial species cause Queensland tick typhus, Flinders Island spotted fever and Australian spotted fever. However, tick-transmitted rickettsiae in various parts of the world have recently been reviewed,14 and the findings emphasise the possibility that Australian clinicians may encounter patients who have returned to Australia after travelling and who present with a tick-borne infection contracted in another country.

The first case of Australian tick typhus was reported in 1946 from north Queensland15 and later that same year a series of cases, including the isolation of the causative agent, Rickettsia australis, from patients was described.16 The organism has since been isolated from a patient in south-east Queensland17 and from I. holocyclus and I. tasmani ticks.18 Queensland tick typhus was the first tick-transmitted infection recognised in Australia. It is seen regularly on the east coast of Australia from the Torres Strait Islands to the south-eastern corner of Victoria. The northern suburbs of Sydney are a particularly common location for transmission of this infection.19,20 Although often a mild condition involving fever, rash and eschar and readily treated with a short course of doxycycline, the infection may be severe21,22 or fatal,23 and may have unusual feaures.24 In north-eastern New South Wales, 15.4% of paralysis ticks contained R. australis.13 Hence, being bitten by this tick, in this location, appears to offer a 1 in 6 risk of being infected with the rickettsia.

A different rickettsial infection (Flinders Island spotted fever) has been observed in patients from Flinders Island, Tasmania.25,26 R honei was isolated from febrile patients27 and shown to be genetically different from R. australis. The tick vector was the southern reptile tick, which is known to bite humans, and on Flinders Island, 63% of these ticks were found to contain R. honei.28 Flinders Island spotted fever is now known to also occur in South Australia,29,30 Western Australia31 and other parts of the world.14

A related bacterium, Rickettsia honei subsp. marmionii, causes a similar infection, Australian spotted fever, and has been detected in the ticks I. tasmani (unpublished data) and Haemaphysalis novaeguineae in Queensland,32 and has been associated with several cases of human disease in eastern Australia.33

Two further species of rickettsia identified in Australian ticks may be considered potential human pathogens, although their presence in febrile patients is yet to be confirmed. Rickettsia gravesii has been detected in ornate kangaroo ticks in WA34 and Queensland (unpublished data). In a WA study, rogainers (outdoor recreationists) had a significantly higher seroprevalence to spotted fever group rickettsiae than controls with minimal bush exposure,35 suggesting exposure to a possible tick-transmitted rickettsia. A Tasmanian study found that 55% of I. tasmani ticks collected from Tasmanian devils contained rickettsial DNA. Further molecular characterisation of the DNA demonstrated sufficient divergence from previously described species to designate this new organism Candidatus Rickettsia tasmanensis.36 Because I. tasmani is known to bite humans, this rickettsia must be considered as a potential human pathogen.

Coxiella burnetii

This bacterium causes Q fever and usually infects humans by inhalation of infectious aerosols from carrier vertebrate animals such as goats, sheep, cattle and domestic pets. However, it is present in both paralysis ticks13 and ornate kangaroo ticks,37,38 and although, anecdotally, there are other cases of Q fever being transmitted by ticks, there is only one published case where the patient developed pericarditis, a rare presentation of Q fever, after being bitten by an ornate kangaroo tick.39

In north-eastern NSW, 5.6% of paralysis ticks contained the com1 gene of C. burnetii.13 This bacterium has been isolated from the bandicoot tick (Haemaphysalis humerosa) from both sides of Australia,40,41 although it is unlikely that this tick species bites humans.

Other possible bacterial pathogens causing rickettsial illness

Candidatus Neoehrlichia mikurensis has been shown to be a human pathogen in other countries,14 causing febrile illness and post-infection fatigue especially in immunocompromised patients. Recent Australian studies demonstrated the presence of Candidatus Neoehrlichia spp. in paralysis ticks,11,12 but their presence in Australian patients is yet to be shown.

Anaplasma and Ehrlichia species have been detected by molecular means in paralysis and ornate kangaroo ticks,11 and these bacteria from the ornate kangaroo tick in the southwest of WA have been named Anaplasma bovis strain Yanchep and Candidatus Ehrlichia occidentalis, respectively (personal communication, Alex Gofton, PhD student, Vector and Waterborne Pathogens Research Group, Murdoch University, January 2017). Certain species of these bacterial genera are known to be human pathogens (eg, E. chaffeensis, A. phagocytophilum). There is thus a possibility that these Australian bacteria may also be human pathogens.

Although a Borrelia species has been detected in the Australian echidna tick (Bothriocroton concolor),42 this bacterium belongs to a unique clade unrelated to the Borrelia species responsible for causing Lyme disease. This tick is not known to bite humans, so the bacterium is unlikely to be a human pathogen. A Borrelia species detected in native rats was not virulent for a human after experimental challenge.43 Lyme disease bacteria are probably not present in Australian ticks.10,44,45

Fancisella spp. are tick-transmitted bacteria that cause classic tularaemia. The tropical reptile tick from northern Australia (Amblyomma fimbriatum), which is not known to bite humans, has been shown to contain DNA from this bacterium.46 A case of a localised Francisella infection following a bite from a ring-tail possum has been reported,47 but it is not yet clear whether tularaemia is a tick-transmitted infection in Australia.

Protozoal infections

Babesia spp. are recognised human and animal pathogens transmitted by tick bites, especially in the northern hemisphere. In Australia, cattle are often infected with B. bigemina and/or B. bovis (cattle tick fever) via the bite of the Australian cattle tick (Rhipicephalus australis); and dogs with B. vogeli and/or B. gibsoni via the brown dog tick (R. sanguineus) and possibly the bush tick (Haemaphysalis longicornis).48,49 Only the bush tick is thought to bite humans.

A single case of human babesiosis caused by B. microti has been described in an Australian man who lived in close proximity to dogs but who did not recall being bitten by a tick and had not travelled outside of Australia for nearly 40 years.49 This was thought to have been a locally acquired infection, but there have been no subsequent cases of human babesiosis diagnosed in Australia.

Allergy following tick bites

A local allergic reaction to ticks is not uncommon and may take the form of urticaria or induration (due to tick saliva), scrub itch (due to infestations of nymphs) or rash.50–52

Occasionally, the allergic reaction can be systemic, including wheezing, anaphylaxis and even death.53 Severe allergy has recently been described following prior sensitisation of a patient due to the ingestion of red meat.54

Paralysis following tick bites

I. holocyclus is known as the Australian paralysis tick because it injects a mixture of neurotoxins into its host when it bites. The role of these toxins for the tick is uncertain, but they often have a profound impact on the host animal. The toxins, known as holocyclotoxins, are small, cyclic polypeptides similar to botulinum toxin. They can affect native animals, family pets and occasionally humans, especially if they are small,55,56 and may cause ataxia followed by an ascending, symmetrical, flaccid paralysis similar to Guillain-Barré syndrome. Cranial nerves may be involved, leading to facial paralysis or ophthalmoplegia. The paralysis can extend even after the tick has been removed. There have been human deaths due to tick toxin, but not for many decades.55

Autoimmunity following tick bites

There is one report of Graves’ disease developing in a patient bitten by an unknown species of Australian tick in WA.57 The patient also had mild rickettsial infection following the bite. It was hypothesised that molecular homology between the thyroid-secreting hormone receptor of the patient and the rickettsial ATPase enzyme resulted in the synthesis of an antibody that cross-reacted with the host thyroid receptor, leading to increased synthesis of thyroid hormones.

Post-infection fatigue

This phenomenon is well known to be a consequence of several infections (eg, Ross River virus infection, Q fever, Epstein-Barr virus infection), although the antecedent infection may not be clearly identified by the patient. It is not yet widely recognised as a problem following rickettsial infection, although it has been suggested by a study involving two large cohorts of fatigued and non-fatigued patients,58 and a case report.59 In addition, there was a report of endemic typhus in SA,60 where patients often had a prolonged fatigue-like condition.

Australian multisystem disorder

This term has been proposed to describe patients with a range of symptoms of currently unknown aetiology, although they have been linked to tick bites in Australia.45 The main symptoms are fatigue, joint and muscle pain, and neurocognitive impairment, but vary from patient to patient. This is the group of patients who may have described themselves as having chronic Lyme (or Lyme-like) disease.44

Because so little is known about the medical effects of tick bites in Australia, it is important for medical practitioners to keep an open mind when dealing with patients who speak of problems associated with tick bites. While the patient may well have other underlying medical issues brought to light by the tick bite, a considered investigation of the whole clinical story is indicated.

If the tick bite is recent (eg, within 4 weeks) and the patient is symptomatic, an EDTA blood sample should be sent to a diagnostic laboratory for microbial polymerase chain reaction testing and culture, accompanied by a serum sample for antibody testing. This acute serum should be stored by the laboratory and tested in parallel with a later serum from the patient, looking for seroconversion or a significant rise in antibody titre, if the patient continues to be unwell and has not responded to treatment. The second (convalescent) serum is an important sample, as it may well contain antibodies to the causative microbe that were absent in the first (acute) serum.

However, when the tick bite has occurred some time ago (more than 8 weeks), serology is difficult to interpret, because antibody titres are stable and may reflect either recent or long-past infection.

In relation to Lyme disease, given the likely absence of the relevant bacteria in Australian ticks,10,44,45 there is little value in laboratory testing for the disease if the patient has not been to an endemic region of the world.

Conclusion

Much remains to be learned about the medical consequences of tick bites in Australia. While rickettsial infections are currently the most commonly known, it is likely that ongoing research will reveal new tick-borne viral, bacterial and protozoal infections, including the possibility of zoonotic transmission from wild and domestic mammals and birds which have been bitten by ticks.

This highlights the importance of the One Health concept (https://www.cdc.gov/onehealth), which recognises the importance of the interaction between human health, animal health and the environment, and will enable the identification of new and emerging diseases.

Box –
Australian tick species known to bite humans, and associated pathogens and diseases

Tick species

Common name

Known human pathogen

Disease

Possible human pathogen

Ixodes holocyclus

Paralysis tick (scrub tick in Queensland)

Rickettsia australis

Queensland tick typhus

Candidatus Neoehrlichia spp.

Coxiella burnetii

Q fever

Bartonella henselae; Ehrlichia spp.

Ixodes tasmani

Common marsupial tick

R. australis

Queensland tick typhus

Candidatus R. tasmanensis

R. honei subsp. marmionii

Australian spotted fever

Bartonella spp.

Ixodes cornuatus

Southern paralysis tick

R. australis

Queensland tick typhus

Amblyomma triguttatum

Ornate kangaroo tick

C. burnetii

Q fever

R. gravesii; Anaplasma sp.; Ehrlichia sp.

Bothriocroton hydrosauri

Southern reptile tick

R. honei

Flinders Island spotted fever

Haemaphysalis novaeguinae

No common name

R. honei subsp. marmionii

Australian spotted fever

Haemaphysalis longicornis

Bush tick (introduced, not native to Australia)

Babesia sp.

Ornithodoros capensis

Seabird soft tick

Virus

Controversies in diagnosis and management of community-acquired pneumonia

Community-acquired pneumonia (CAP) continues to generate a large amount of interest, both for the clinician and the researcher. It is a very frequent diagnosis and the leading infection-related cause of death in most developed countries.1

Although CAP is a relatively common infection, there are wide disparities in its management, including the class of antibiotics chosen, the duration of therapy and the role of adjunctive therapy such as corticosteroids. In this review, we assess the evidence for the approaches to some of these clinical questions regarding CAP management. We agree with the Australian antibiotic guidelines2 regarding recommended antibiotics. Therefore, we do not specifically consider the question of the most appropriate class of antibiotics for treating patients with CAP — the Box summarises the antibiotics commonly used in Australia.

We used a PubMed search for original and review articles from 2005 to 2017, and reviewed specialist society publications and guidelines from Australia and overseas, to formulate an evidence-based overview of the topic as applied to clinical practice.

Are we overdiagnosing CAP?

Although it may seem self-evident, an essential question in the management of patients with CAP is whether the diagnosis is in fact correct. CAP can present in variable ways, some of which are similar to other conditions such as acute bronchitis, viral respiratory tract infections and cardiac failure. Patients with dementia, who are more likely to develop CAP, may not be able to give a reliable description of symptoms.3 Patients may present with two or more conditions at once, confusing the diagnostic process.3 This may occur as a coincidence or alternatively be due to a cause–effect relationship between them. Examples of the latter include that a chest infection can precipitate either an exacerbation of cardiac failure or an acute coronary syndrome.4 In addition, particularly in the era of the 4-hour National Emergency Access Target, staff members in the emergency department (ED) are under greater pressure to move patients out of the ED and thus may need to change the focus of their assessment to “does this patient need admission?” rather than “what is the correct diagnosis?”.

From clinical studies of CAP performed in Australia, of all the patients screened for inclusion on the basis of being given the label of CAP in the ED, a large proportion are subsequently excluded from the study because their chest x-ray is not consistent with CAP.5,6 This issue is not limited to Australia, with international studies showing that chest x-rays reported by treating clinicians as being consistent with CAP are not confirmed as being so by a radiologist in 20–50% of cases.7–11

There are several downsides to excessive diagnosis of CAP. The most obvious is the use of unnecessary antibiotics in patients who have conditions that do not require antibiotics such as viral respiratory infections or cardiac failure. This has the potential to add to the problem of antibiotic resistance as well as putting the patient at risk of antibiotic-related complications such as Clostridium difficile-associated diarrhoea. A further issue, particularly when cultures are not performed in patients initially labelled as having CAP, is the potential delay in diagnosis and inappropriate antibiotic therapy of those patients whose true diagnosis is something more serious, such as sepsis, infective endocarditis or pulmonary embolism. Some of these misdiagnosed patients can have their admission prolonged by many days due to the non-performance of blood cultures. We believe that the diagnostic uncertainty for admitted patients initially given the diagnosis of CAP means that recommendations that discourage the performance of blood cultures in CAP patients are inappropriate.12–15

Duration of antibiotic therapy

The optimal duration of antimicrobial therapy for CAP is another area of controversy. The tendency in hospitals appears to be to overtreat rather than undertreat, often with a long oral tail.16–18 Whether this is a case of believing that “more is better” or due to the disparity between the time to clinical resolution compared with microbiological resolution, the excessive prescription of antibiotics puts the patient at greater risk of side effects and colonisation with resistant organisms, including nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae.19,20 Ecologically, the prescription of antibiotics for respiratory infection contributes to a rise in resistance in the community.21

Should the physician turn to national guidelines for advice on duration and choice of antibiotic (Box); the Australian Therapeutic guidelines: antibiotic recommend 7 days of total therapy for moderate and most cases of severe pneumonia,2 as does the British Thoracic Society,22 while the United Kingdom NICE guidelines suggest 5 days for mild CAP and 7–10 days for moderate to severe CAP.23 However, the Infectious Diseases Society of America (IDSA) supports a 5-day treatment for inpatient CAP, provided the patient is afebrile and clinically improving.24 So, with all this variation, which is correct?

There is agreement that a 7-day course of an antibiotic is effective for most cases of CAP, and this is relatively non-controversial, albeit adhered to poorly.25 There is increasing evidence, however, that shorter courses of 5 or even 3 days’ therapy may be just as effective. Overseas literature provides support for short course therapy with azithromycin, including as little as a single dose.26 This likely relates to the high tissue penetration and persistence of adequate tissue levels of this macrolide for some days following administration.27 A multicentre randomised clinical trial evaluating the safety of the IDSA recommendations found that a 5-day course of therapy is safe and effective, although most patients received quinolone antibiotics, a class of antibiotic rarely used in Australia for treating CAP.28 Regarding the β-lactam therapy that would be more likely prescribed in the Australian setting, a 3-day course of intravenous (IV) amoxycillin monotherapy has been shown to be as effective as 3 days of IV amoxycillin followed by 5 days of oral amoxycillin in adult patients who were improving at 72 hours.29 Two previous studies reached a similar conclusion in paediatric populations.30,31

Given the accumulating evidence, we suggest that a 5-day course of antibiotics should be effective in most cases of uncomplicated CAP, even though complete symptom resolution is unlikely to have occurred at this time point. For patients on IV therapy who are clinically improving at 72 hours, a switch to oral therapy is appropriate, but clinicians should keep in mind that the oral antibiotics should complete the 5-day total course and not add another 5 days to what has already been prescribed. If improvement has been rapid in the first 72 hours, it would be reasonable to cease all therapy at 3 days, provided close follow-up is available.

Some international studies have suggested that bundles of care for patients with CAP, which include antibiotic administration within 4 to 8 hours of presentation, may lead to better patient outcomes.32–34 However, it is not clear that this would provide benefits in the Australian setting. In relation to the United States studies,33,34 this finding may reflect past differences in the US health system, where antibiotics may not have been given until the patient was seen by their attending physician, potentially leading to delays in therapy. The US recommendations have now changed to recommend commencement of antibiotics while the patient is in the ED.24 This is already the norm in Australia.

Other studies35,36 have suggested that increases in mortality in patients with CAP may be due to an atypical presentation which leads to a delay in diagnosis, rather than being associated with a delay in antibiotic administration. When this was taken into account in one study, the association between a delay in antibiotic administration beyond 4 hours and increased mortality was not statistically significant.35

Potential cardiac side effects of newer macrolide antibiotics

A 2012 study reported an excess of both cardiovascular and all-cause deaths in patients with pneumonia treated with a 5-day course of azithromycin compared with those treated with other antimicrobials, potentially related to its ability to prolong the QT interval.37 As a result, in 2013, the US Food and Drug Administration issued a warning regarding prescription of azithromycin for CAP, even though that study had a number of limitations, including its non-randomised nature and outpatient study population.

However, the case was far from closed, and results from other retrospective studies reached the opposite conclusion. Mortensen and colleagues studied older patients with CAP and found that those treated with macrolides had a lower rate of mortality, in spite of a small rise in rates of myocardial infarction “consistent with a net benefit”.38 This conclusion was shared by Cheng and colleagues in their 2015 meta-analysis.39 In 2016, a Canadian population-based retrospective cohort study involving about one million adults aged over 65 years found no increase in rates of cardiac arrhythmias at 30 days, in addition to lower all-cause mortality, in patients treated with a macrolide antibiotic.40

Given the evidence that the benefit of using macrolide therapy outweighs potential cardiac risk, we support recommendations to use a macrolide in place of doxycycline for atypical cover when the latter cannot be used, and the use of azithromycin in combination therapy for severe hospitalised CAP, such as that requiring management in an intensive care unit (ICU). We also point out the excellent oral bioavailability of oral azithromycin,27 and recommend its use in preference to the IV formulation in patients for whom oral therapy is tolerated and expected to be absorbed.

The link between CAP and cardiovascular disease

In recent years, evidence has emerged regarding the role of inflammatory conditions in the development of cardiovascular disease such as myocardial infarctions and strokes.41 It is postulated that inflammation, especially when persistent, may have an effect on vascular plaques, making them more unstable or prone to acute occlusion.42,43 Various infections including CAP, influenza and human immunodeficiency virus, as well as other sources of chronic inflammation such as rheumatoid arthritis, have all been shown to be associated with higher rates of acute cardiovascular disease and deaths.4,44–51

In a large study, in the 30 days following an episode of CAP requiring inpatient care, incidence of worsening heart failure, cardiac arrhythmia and acute myocardial infarction were 21%, 10% and 3% respectively.4 However, it is important to note that the problem does not end after 30 days. There is a measurably higher rate of cardiovascular deaths in the following few years, when patients admitted with CAP are compared with matched cohorts admitted with non-infection-related conditions. The rate increases most in older patients (aged over 40 years) and those with greater number of cardiovascular risk factors.52

The mechanism of this increase in cardiovascular complications during and after the CAP episode appears to be multifactorial. Inflammation is a pro-thrombotic state; myocardial inflammation and damage may occur, potentially in response to NADPH oxidase 2 upregulation; cardiac strain may be present in the setting of increased sympathetic nervous system activity with relative hypoxia caused by the lung consolidation; increased fluid and sodium loading associated with some IV antibiotic may worsen fluid overload problems in some cardiac failure patients; and QT interval prolongation with the use of other antibiotics may contribute to arrhythmic potential.46,47,53

What remains to be seen is whether we can act on this in a useful way. It is notable that the vast majority of patients who die from CAP are very old with multiple comorbidities, for whom death may be an expected terminal event. While acutely addressing cardiac risk factors with, for example, the addition of anti-platelet agents like aspirin or cholesterol-lowering statin therapy has not yet been shown to alter mortality in the acute setting,54 it would appear prudent to assess whether such treatments are indicated in patients admitted with CAP, especially if they are aged over 40 years.52

The role of corticosteroids in the management of CAP

Given that the inflammatory state during and after an episode of CAP appears to have an important role in contributing to both morbidity and mortality,4,44–47 there has been interest in the role of inflammatory modulators such as corticosteroids as adjunctive CAP therapy. Levels of cytokines vary with severity of CAP and highest levels of the pro-inflammatory cytokine interleukin (IL)-6 and the anti-inflammatory cytokine IL-10 are associated with higher chance of dying from severe CAP.55 Glucocorticoids reduce the levels of such cytokines,56 and thus are theoretically attractive as a means to reduce CAP mortality.

There have been a number of attempts to address the question about whether this theoretical benefit may be true. Individual studies have varied in terms of the severity of the CAP studied, the choice of corticosteroid used, the route by which it was given, its dose and duration, and the outcomes measured. Results have been mixed, and several attempts at performing meta-analyses on these studies — with all the expected problems associated with attempting to combine such a heterogeneous collection of methodologies — have shown marginal benefits in terms of mortality, particularly in patients with the most severe CAP managed in the ICU, as well as a shorter time to becoming afebrile.57–60 These small benefits need to be weighed against the potential downside of high-dose corticosteroids, both in terms of potential side effects like immune suppression and also the fact that outcomes may have been worse in patients whose infection was caused by an influenza virus or Aspergillus.61,62

Thus, the potential role of corticosteroids as adjunctive therapy in CAP appears to be very limited. They could be considered in patients with CAP severe enough to require management in the ICU, but caution should be taken until the aetiology is known, particularly during influenza season. Their use should also be very carefully considered in patients at higher risk from corticosteroid complications, such as the immunocompromised, women who are pregnant, patients with recent gastrointestinal haemorrhages, and patients at greater risk of neuropsychiatric problems.59 The possible shortened time to defervescence is not sufficiently clinically useful to justify the potential harm from such therapy.

Conclusion

In this era of burgeoning antibiotic resistance, the treatment of CAP is an area where we have the potential to reduce antibiotic consumption. We are diagnosing it too often and treating it for too long. Most non-ICU patients with CAP could be treated for 3–5 days in total.

CAP is a common cause of death, both in the short term and also in the subsequent few years, and many of these deaths appear to be cardiovascular related. Although most deaths from CAP occur in very old people with multiple comorbidities — and so may not easily be prevented — the management of a patient with CAP should be seen as an opportunity to address and treat cardiac risk factors when they are present.

Box –
Antibiotics commonly used to treat community-acquired pneumonia (CAP) in Australia2

CAP severity

Antibiotic

Comments

Suggested duration

Mild (treated as outpatient)

Doxycycline

Monotherapy; avoid in pregnancy and young children

3–5 days

Amoxycillin

Monotherapy; side effect profile better than amoxycillin–clavulinate and spectrum of activity more appropriate

3–5 days

Macrolide (eg, clarithromycin, azithromycin or roxithromycin)

Monotherapy; potential option when patient intolerant of doxycycline and amoxycillin

3–5 days

Amoxycillin–clavulinate

Consider in patients from nursing homes or following recent hospital admissions

5 days

Cefuroxime*

Consider in patients with non-hypersensitivity reactions to amoxycillin

3–5 days

Moderate (admitted patients not requiring ICU)

Benzylpenicillin

Use in combination with either doxycycline or a macrolide

Switch to oral therapy when clinical improvement occurs, generally in 1–3 days

Doxycycline

Oral; used in combination with benzylpenicillin

5 days

Macrolide (eg, clarithromycin or azithromycin)

Alternative second agent to doxycycline (oral or IV); used in combination with benzylpenicillin

5 days

Moxifloxacin

Use as monotherapy if hypersensitivity reaction to penicillins; excellent oral bioavailability

5 days

Severe (patients potentially requiring ICU care)

Ceftriaxone plus azithromycin IV

Alternative choices may be appropriate in tropical northern Australia

7 days

ICU = intensive care unit. IV = intravenous. * Cefaclor is not useful owing to poor antibacterial activity and high rate of causing rashes; cephalexin is not ideal given the poor spectrum of activity against respiratory pathogens.

The Australasian Society for Infectious Diseases and Refugee Health Network of Australia recommendations for health assessment for people from refugee-like backgrounds: an abridged outline

There are currently more than 65 million people who have been forcibly displaced worldwide, including 21.3 million people with formal refugee status, over half of whom are aged under 18 years.1 More than 15 000 refugees have resettled in Australia in the 2015–16 financial year, which includes a proportion of the 12 000 refugees from Syria and Iraq recently added to Australia’s humanitarian intake.2 In addition, around 30 000 asylum seekers who arrived by plane or boat are currently in Australia awaiting visa outcomes.3

People from refugee-like backgrounds are likely to have experienced disruption of basic services, poverty, food insecurity, poor living conditions and prolonged uncertainty; they may have experienced significant human rights violations, trauma or torture. These circumstances place them at increased risk of complex physical and mental health conditions. They face numerous barriers to accessing health care after arrival in Australia, such as language, financial stress, competing priorities in the settlement period, and difficulties understanding and navigating the health care system.4–6 Most people require the assistance of an interpreter for clinical consultations.7 Offering a full health assessment to newly arrived refugees and asylum seekers is a positive step towards healthy settlement, and helps manage health inequity through the provision of catch-up immunisation and the identification and management of infectious and other health conditions.

These guidelines update the Australasian Society of Infectious Diseases (ASID) guidelines for the diagnosis, management and prevention of infectious diseases in recently arrived refugees8 published in 2009 and previously summarised in the MJA.9 When these recommendations were first published, more than 60% of humanitarian entrants arriving in Australia were from sub-Saharan Africa10 and had a high prevalence of malaria, schistosomiasis and hepatitis B virus (HBV) infection.11–15 The initial guidelines were primarily intended to help specialists and general practitioners to diagnose, manage and prevent infectious diseases. Since then, there have been changes in refugee-source countries — with more arrivals from the Middle East and Asia and fewer from sub-Saharan Africa16,17 — and an increased number of asylum seekers arriving by boat,18 alongside complex and changing asylum seeker policies and changes in health service provision for these populations. In this context, we reviewed the 2009 recommendations to ensure relevance for a broad range of health professionals and to include advice on equitable access to health care, regardless of Medicare or visa status. The revised guidelines are intended for health care providers caring for people from refugee-like backgrounds, including GPs, refugee health nurses, refugee health specialists, infectious diseases physicians and other medical specialists.

This article summarises the full guidelines, which contain detailed literature reviews, recommendations on diagnosis and management along with explanations, supporting evidence and links to other resources. The full version is available at http://www.asid.net.au/documents/item/1225.

Methods

The guideline development process is summarised in Box 1. The two key organisations developing these guidelines are ASID and the Refugee Health Network of Australia. ASID is Australia’s peak body representing infectious diseases physicians, medical microbiologists and other experts in the fields of the prevention, diagnosis and treatment of human and animal infections. The Refugee Health Network is a multidisciplinary network of health professionals across Australia with expertise in refugee health.20

We defined clinical questions using the PIPOH framework (population, intervention, professionals, outcomes and health care setting).21 The chapter authors and the Expert Advisory Group developed recommendations based on reviews of available evidence, using systematic reviews where possible. Australian prevalence data also informed screening recommendations; for example, the low reported prevalence of chlamydia (0.8–2.0%) infections and absence of gonorrhoea infections in refugee cohorts in Australia13,22–24 (and in other developed countries25–27) informed the new recommendation for risk-based sexually transmitted infection (STI) screening.

Despite the intention to assign levels of evidence to each recommendation, there was limited published high level evidence in most areas, and virtually all recommendations are based on expert consensus. Consensus was not reached regarding the recommendations relating to human immunodeficiency virus (HIV) and STIs.

The term “refugee-like” is used to describe people who are refugees under the United Nations Refugee Convention,28 those who hold a humanitarian visa, people from refugee-like backgrounds who have entered under other migration streams, and people seeking asylum in Australia. “Refugee-like” acknowledges that people may have had refugee experience in their countries of origin or transit, but do not have formal refugee status.

Current pre-departure screening

All permanent migrants to Australia have a pre-migration immigration medical examination 3–12 months before departure,29 which includes a full medical history and examination. Investigations depend on age, risk factors and visa type,30 and include:

  • a chest x-ray for current or previous tuberculosis ([TB]; age ≥ 11 years);

  • screening for latent TB infection with an interferon-γ release assay or tuberculin skin test (for children aged 2–10 years, if they hold humanitarian visas, come from high prevalence countries or have had prior household contact);

  • HIV serology (age ≥ 15 years, unaccompanied minors);

  • hepatitis B surface antigen (HBsAg) testing (pregnant women, unaccompanied minors, onshore protection visas, health care workers);

  • hepatitis C virus (HCV) antibody testing (onshore protection visas, health care workers); and

  • syphilis serology (age ≥ 15 years, humanitarian visas, onshore protection visas).

Humanitarian entrants are also offered a voluntary pre-departure health check depending on departure location and visa subtype.31 The pre-departure health check includes a rapid diagnostic test and treatment for malaria in endemic areas; empirical treatment for helminth infections with a single dose of albendazole; measles, mumps and rubella vaccination; and yellow fever and polio vaccination where relevant. The current cohort of refugees arriving from Syria will have extended screening incorporating the immigration medical examination and pre-departure health check, with additional mental health review and immunisations.

People seeking asylum who arrived by boat have generally had a health assessment on arrival in immigration detention — although clinical experience suggests that investigations and detention health care varies, especially for children. However, asylum seekers who arrived by plane will not have had a pre-departure immigration medical examination.

General recommendations

Our overarching recommendation is to offer all people from refugee-like backgrounds, including children, a comprehensive health assessment and management plan, ideally within 1 month of arrival in Australia. This assessment can be offered at any time after arrival if the initial contact with a GP or clinic is delayed, and should also be offered to asylum seekers after release from detention. Humanitarian entrants who have been in Australia for less than 12 months are eligible for a GP Medicare-rebatable health assessment. Such assessments may take place in a primary care setting or in a multidisciplinary refugee health clinic. Documented overseas screening and immunisations, and clinical assessment should also guide diagnostic testing.

Health care providers should adhere to the principles of person-centred care when completing post-arrival assessments.32,33 These include: respect for the patient’s values, preferences and needs; coordination and integration of care with the patient’s family and other health care providers; optimising communication and education, provision of interpreters where required (the Doctors Priority Line for the federal government-funded Translating and Interpreting Service is 1300 131 450) and use of visual and written aids and teach-back techniques to support health literacy.34 It is important to explain that a health assessment is voluntary and results will not affect visa status or asylum claims.

Specific recommendations

Recommendations are divided into two sections: infectious and non-infectious conditions. Box 2 provides a checklist of all recommended tests, and Box 3 sets out details of country-specific recommendations. A brief overview is provided below. For more detailed recommendations regarding management, follow-up and considerations for children and in pregnancy, see the full guidelines.

Infectious conditions

TB:

  • Offer latent TB infection testing with the intention to offer preventive treatment and follow-up.

  • Offer screening for latent TB infection to all people aged ≤ 35 years.

  • Children aged 2–10 years may have been screened for latent TB infection as part of their pre-departure screening.

  • Screening and preventive treatment for latent TB infection in people > 35 years will depend on individual risk factors and jurisdictional requirements in the particular state or territory.

  • Use either a tuberculin skin test or interferon-γ release assay (blood) to screen for latent TB infection.

  • A tuberculin skin test is preferred over interferon-γ release assay for children < 5 years of age.

  • Refer patients with positive tuberculin skin test or interferon-γ release assay results to specialist tuberculosis services for assessment and exclusion of active TB and consideration of treatment for latent TB infection.

  • Refer any individuals with suspected active TB to specialist services, regardless of screening test results.

Malaria:

  • Investigations for malaria should be performed for anyone who has travelled from or through an endemic malaria area (Box 3), within 3 months of arrival if asymptomatic, or any time in the first 12 months if there is fever (regardless of pre-departure malaria testing or treatment).

  • Test with both thick and thin blood films and an antigen-based rapid diagnostic test.

  • All people with malaria should be treated by, or in consultation with, a specialist infectious diseases service.

HIV:

  • Offer HIV testing to all people aged ≥ 15 years and all unaccompanied or separated minors, as prior negative tests do not exclude the possibility of subsequent acquisition of HIV (note that consensus was not reached regarding this recommendation).

HBV:

  • Offer testing for HBV infection to all, unless it has been completed as part of the immigration medical examination.

  • A complete HBV assessment includes HBsAg, HB surface antibody and HB core antibody testing.

  • If the HBsAg test result is positive, further assessment and follow-up with clinical assessment, abdominal ultrasound and blood tests are required.

HCV:

  • Offer testing for HCV to people if they have:

    • risk factors for HCV;

    • lived in a country with a high prevalence (> 3%) of HCV (Box 3); or

    • an uncertain history of travel or risk factors.

  • Initial testing is with an HCV antibody test. If the result is positive, request an HCV RNA test.

  • If the HCV RNA test result is positive, refer to a doctor accredited to treat HCV for further assessment.

Schistosomiasis:

  • Offer blood testing for Schistosoma serology if people have lived in or travelled through endemic countries (Box 3).

  • If serology is negative, no follow-up is required.

  • If serology is positive or equivocal:

    • treat with praziquantel in two doses of 20 mg/kg, 4 hours apart, orally; and

    • perform stool microscopy for ova, urine dipstick for haematuria, and end-urine microscopy for ova if there is haematuria.

  • If ova are seen in urine or stool, evaluate further for end-organ disease.

Strongyloidiasis:

  • Offer blood testing for Strongyloides stercoralis serology to all.

  • If serology is positive or equivocal:

    • check for eosinophilia and perform stool microscopy for ova, cysts and parasites; and

    • treat with ivermectin 200 μg/kg (weight ≥ 15 kg), on days 1 and 14 and repeat eosinophil count and stool sample if abnormal.

  • Refer pregnant women or children < 15 kg for specialist management.

Intestinal parasites:

  • Check full blood examination for eosinophilia.

  • If pre-departure albendazole therapy is documented:

    • if there are no eosinophilia and no symptoms, no investigation or treatment is required; and

    • if there is eosinophilia, perform stool microscopy for ova, cysts and parasites, followed by directed treatment.

  • If no documented pre-departure albendazole therapy, depending on local resources and practices, there are two acceptable options:

    • empirical single dose albendazole therapy (age > 6 months, weight < 10 kg, dose 200 mg; weight ≥ 10 kg, dose 400 mg; avoid in pregnancy, class D drug); or

    • perform stool microscopy for ova, cysts and parasites, followed by directed treatment.

Helicobacter pylori:

  • Routine screening for H. pylori infection is not recommended.

  • Screen with either stool antigen or breath test in adults from high risk groups (family history of gastric cancer, symptoms and signs of peptic ulcer disease, or dyspepsia).

  • Children with chronic abdominal pain or anorexia should have other common causes of their symptoms considered in addition to H. pylori infection.

  • Treat all those with a positive test (see the full guidelines for details, tables 1.5 and 9.1).

STIs:

  • Offer an STI screen to people with a risk factor for acquiring an STI or on request. Universal post-arrival screening for STIs for people from refugee-like backgrounds is not supported by current evidence.

  • A complete STI screen includes a self-collected vaginal swab or first pass urine nucleic acid amplification test and consideration of throat and rectal swabs for chlamydia and gonorrhoea, and serology for syphilis, HIV and HBV.

  • Syphilis serology should be offered to unaccompanied and separated children < 15 years.

Skin conditions:

  • The skin should be examined as part of the initial physical examination.

  • Differential diagnoses will depend on the area of origin (see table 11.1 in full guidelines for details).

Immunisation:

  • Provide catch-up immunisation so that people of refugee background are immunised equivalent to an Australian-born person of the same age.

  • In the absence of written immunisation documentation, full catch-up immunisation is recommended.

  • Varicella serology is recommended for people aged ≥ 14 years if there is no history of natural infection.

  • Rubella serology should be completed in women of childbearing age.

Non-infectious conditions

Anaemia and other nutritional problems:

  • Offer full blood examination screening for anaemia and other blood conditions to all.

  • Offer screening for iron deficiency with serum ferritin to children, women of childbearing age, and men who have risk factors.

  • Check vitamin D status as part of initial health screening in people with one or more risk factors for low vitamin D.

  • People with low vitamin D should be treated to restore their levels to the normal range with either daily dosing or high dose therapy, paired with advice about sun exposure.

  • Consider screening for vitamin B12 deficiency in people with history of restricted food access, especially those from Bhutan, Afghanistan, Iran and the Horn of Africa.

Chronic non-communicable diseases in adults:

  • Offer screening for non-communicable diseases in line with the Royal Australian College of General Practitioners Red Book35 recommendations, including assessment for:

    • smoking, nutrition, alcohol and physical activity;

    • obesity, diabetes, hypertension, cardiovascular disease, chronic obstructive pulmonary disease and lipid disorders; and

    • breast, bowel and cervical cancer.

  • Assess diabetes and cardiovascular disease risk earlier for those from regions with a higher prevalence of non-communicable diseases, or those with an increased body mass index or waist circumference.

Mental health:

  • A trauma informed assessment of emotional wellbeing and mental health is part of post-arrival screening. Being aware of the potential for past trauma and impact on wellbeing is essential, although it is generally not advisable to ask specifically about details in the first visits.

  • Consider functional impairment, behavioural difficulties and developmental progress as well as mental health symptoms when assessing children.

Hearing, vision and oral health:

  • A clinical assessment of hearing, visual acuity and dental health should be part of primary care health screening.

Women’s health:

  • Offer women standard preventive screening, taking into account individual risk factors for chronic diseases and bowel, breast and cervical cancer.

  • Consider pregnancy and breastfeeding and offer appropriate life stage advice and education, such as contraceptive advice where needed, to all women, including adolescents.

  • Practitioners should be aware of clinical problems, terminology and legislation related to female genital mutilation or cutting and forced marriage.

Box 1 –
Guideline development process

  • An EAG, consisting of refugee health professionals, was formed and it included two ID physicians, an ID and general physician, two GPs, a public health physician, a general paediatrician and a refugee health nurse. An editorial subgroup was also formed.
  • The EAG determined the list of priority conditions in consultation with refugee health specialists and RACGP Refugee Health Special Interest Group clinicians, incorporating information from consultations with refugee background communities19 and previous ASID refugee health guidelines.
  • Each condition was assigned to a primary specialist author with paediatrician and primary care or specialist co-authors. Twenty-eight authors from six states and territories were involved in writing the first draft.
  • The EAG reviewed the first draft to ensure consistency with the framework and the rest of the guidelines. They were then revised by the primary authors.
  • External expert review authors reviewed the second draft and they were then revised by the primary authors.
  • The EAG and the refugee health nurse subcommittee reviewed the third draft.
  • The stakeholders reviewed the fourth draft: ASID, NTAC, RHeaNA, RACGP Refugee Health Special Interest Group, RACP, RACP AChSHM, the Victorian Foundation for the Survivors of Torture, the Multicultural Centre for Women’s Health, the Asylum Seeker Resource Centre, the Ethnic Communities Council of Victoria and community members.
  • The comments from the stakeholders were returned to the authors for review and the EAG compiled the final version.
  • ASID, RACP, NTAC and AChSHM endorsed the final version.

AChSHM = Australasian Chapter of Sexual Health Medicine. ASID = Australasian Society for Infectious Diseases. EAG = Expert Advisory Group. GP = general practitioner. ID = infectious diseases. NTAC = National Tuberculosis Advisory Council. RACGP = Royal Australian College of General Practitioners. RACP = Royal Australasian College of Physicians. RHeaNA = Refugee Health Network of Australia. Adapted from the ASID and RHeaNA Recommendations for comprehensive post-arrival health assessment for people from refugee-like backgrounds (2016; https://www.asid.net.au/documents/item/1225) with permission from ASID.

Box 2 –
Short checklist of recommendations for post-arrival health assessment of people from refugee-like backgrounds

Offer test to

Test

Comments and target condition

All

Full blood examination

Anaemia, iron deficiency, eosinophilia

Hepatitis B serology (HBsAg, HBsAb, HBcAb)

HBsAg testing introduced overseas in 2016 for Syrian and Iraqi refugee cohort and may have been completed in other groups

Strongyloides stercoralis serology

Strongyloidiasis

HIV serology*

≥ 15 years or unaccompanied or separated minor
Also part of IME for age ≥ 15 years

TST or IGRA

Offer test if intention to treat. All ≤ 35years; if≥ 35 years, depends on risk factors and local jurisdiction. TST preferred for children < 5 yearsTST or IGRA testing introduced in 2016 as part of IME for children 2–10 years (humanitarian entrants, high prevalence countries, prior household contact)
LTBI

Varicella serology

≥ 14 years if no known history of disease
Determine immunisation status

Visual acuity

Vision status, other eye disease

Glaucoma assessment

Africans > 40 years and others > 50 years

Dental review

Caries, periodontal disease, other oral health issues

Hearing review

Hearing impairment

Social and emotional wellbeing and mental health

Mental illness, trauma exposure, protective factors

Developmental delay or learning concerns

Children and adolescents
Developmental issues, disability, trauma exposure

Preventive health as per RACGP35

Non-communicable diseases, consider screening earlier than usual age

Catch-up vaccinations

Vaccine preventable diseases, including hepatitis B

Risk-based

Rubella IgG

Women of childbearing age
Determines immunisation status

Ferritin

Men who have risk factors, women and childrenIron deficiency anaemia

Vitamin D, also check calcium, phosphate, and alkaline phosphatase in children

Risk factors if dark skin or lack of sun exposure
Low vitamin D, rickets

Vitamin B12

Arrival < 6 months, food insecurity, vegan diet or from Bhutan, Afghanistan, Iran or Horn of Africa
Nutritional deficiency, risk for developmental disability in infants

First pass urine or self-obtained vaginal swabs for gonorrhoea and chlamydia PCR

Risk factors for STI or on request*

Syphilis serology

Risk factors for STIs, unaccompanied or separated minors. Part of IME in humanitarian entrants aged ≥ 15 years

Helicobacter pylori stool antigen or breath test

Gastritis, peptic ulcer disease, family history of gastric cancer, dyspepsia

Stool microscopy (ova, cysts and parasites)

If no documented pre-departure albendazole or persisting eosinophilia despite albendazoleIntestinal parasites

Country-based (Box 3)

Schistosoma serology

Schistosomiasis

Malaria thick and thin films and rapid diagnostic test

Malaria

HCV Ab, and HCV RNA if HCV Ab positive

HCV, also test if risk factors, regardless of country of origin

HBcAb = hepatitis B core antibody. HBsAb = hepatitis B surface antibody. HBsAg = hepatitis B surface antigen. HCV = hepatitis C virus. HCV Ab = hepatitis C antibody. HIV = human immunodeficiency virus. IGRA = interferon-γ release assay. IME = immigration medical examination. LBTI = latent tuberculosis infection. PCR = polymerase chain reaction. TST = tuberculin skin test. * The panel did not reach consensus on these recommendations. See full guideline at http://www.asid.net.au/documents/item/1225 for details.

Box 3 –
Top 20 countries of origin for refugees and asylum seekers2,3,16 and country-specific recommendations for malaria, schistosomiasis and hepatitis C screening*

Country of birth

Malaria36

Schistosomiasis37

Hepatitis C†38

Afghanistan

No

No

No

Bangladesh

Yes

No

No

Bhutan

Yes

No

No

Burma

Yes

Yes

No

China

No

No

No

Congo

Yes

Yes

Yes

Egypt

No

Yes

Yes

Eritrea

Yes

Yes

No

India

Yes

Yes

No

Iran

No

No

No

Iraq

No

Yes

Yes

Lebanon

No

No

No

Pakistan

Yes

No

Yes

Somalia

Yes

Yes

No

Sri Lanka

Yes

No

No

Stateless‡

Yes

Yes

No

Sudan

Yes

Yes

No

Syria

No

Yes

Consider

Vietnam

No

No

No

* There are regional variations in the prevalence of these conditions within some countries. We have taken the conservative approach of recommending screening for all people from an endemic country rather than basing the recommendation on exact place of residence. Note that some refugees and asylum seekers may have been exposed during transit through countries not listed here. See full guideline for further details. † People with risk factors for hepatitis C should be tested regardless of country of origin. ‡ “Stateless” in this table refers to people of Rohingyan origin. Adapted from the ASID and RHeaNA Recommendations for comprehensive post-arrival health assessment for people from refugee-like backgrounds (2016; https://www.asid.net.au/documents/item/1225) with permission from ASID.

The microbiology of crocodile attacks in Far North Queensland: implications for empirical antimicrobial therapy

Wound infections are common after crocodile attacks and, therefore, prophylactic antimicrobial therapy is advised. However, there are limited data to guide recommendations for the optimal empirical regimen.

In a study from 1992,1 six of 11 survivors of crocodile attacks from Australia’s Northern Territory developed wound infection. The organisms isolated included Aeromonas hydrophila and Enterococcus species, Clostridium species, Pseudomonas aeruginosa and Proteus species, Staphylococcus epidermidis and Burkholderia pseudomallei. As a result, the authors advocated an empirical antibiotic regimen of ceftazidime, penicillin and metronidazole, with the addition of flucloxacillin to treat the patient’s skin flora.1 The Australian Therapeutic Guidelines do not discuss crocodile attacks specifically, but suggest giving oral amoxycillin–clavulanate to people with animal bite wounds at high risk of developing infection, and to patients with established mild infection. For more severe infections, intravenous piperacillin–tazobactam is recommended.2

To validate these recommendations, we reviewed the medical records of 14 of the 15 patients attacked by crocodiles who presented to Cairns Hospital in Queensland, Australia, after 1990 (one chart had been destroyed). Patients were aged 8–70 years and 13 were males. Wild saltwater crocodiles were responsible for seven attacks, farmed saltwater crocodiles for five and wild freshwater crocodiles for two. At presentation, nine patients had wound swabs collected; skin and soft tissue infection was already clinically apparent in four people. Organisms were isolated in six patients where swabs were collected (Box). Eleven of the 14 patients had surgery, with three requiring repeat debridement. Three further patients underwent delayed primary closure and two others required joint washouts. All patients received empirical antibiotics, but the selected agents varied enormously: ceftriaxone was the most commonly prescribed, but metronidazole, gentamicin, doxycycline, cephazolin, flucloxacillin and penicillin were also administered. No patients developed metastatic infection and all survived, although two of them lost digits.

Our findings highlight the diversity of organisms isolated from wounds caused by crocodile attacks. These bacteria can originate from the crocodile’s oral flora, the patient’s skin or can be acquired from the water or soil during the attack. The oral and cloacal flora of Australian crocodiles contain a myriad of organisms, including Aeromonas hydrophila, Pseudomonas aeruginosa, and Proteus and Salmonella species.3 While Aeromonas hydrophila — an organism found in fresh and brackish water — was notably absent in our study, it was the most common isolate in the NT series.1

The excellent outcomes seen in this study are probably primarily explained by prompt, effective surgical care,4,5 but antibiotics may have prevented infective complications. Although the regimen recommended in the NT series would have covered most of the Queensland isolates, it is relatively complex. Based on the isolates in the two series, an empirical regimen of oral amoxycillin–clavulanate for high risk wounds and mild infections would appear appropriate, reserving intravenous piperacillin–tazobactam for more severe infections. These treatments accord with the recommendations of the Australian Therapeutic Guidelines. It is essential to collect tissue cultures to facilitate de-escalation or modification of therapy if rare or resistant organisms, such as Burkholderia pseudomallei or Vibrio species, are isolated. In addition, tetanus should also be considered, with immunisation where appropriate.

Box –
Injuries sustained, surgical intervention and organisms isolated in survivors of crocodile attacks

Patient

Crocodile

Injury sustained

Infection evident

Surgical intervention

Time to debridement (hours)

Empirical antibiotics

Organisms isolated from wound swab

Age (years)

Sex

36

Male

Farmed saltwater

Superficial skin and soft tissue wound of lower limb

Yes

No surgical intervention

N/A

Benzylpenicillin, flucloxacillin, gentamicin

Proteus vulgarisCitrobacter (diversus) koseriGroup G Streptococcus

8

Female

Wild saltwater

Superficial skin and soft tissue wound of torso

No

Debridement and washout, delayed primary closure

8

Ceftriaxone

Candida albicans*

60

Female

Wild saltwater

Fracture, deep skin and soft tissue wound of upper limb and face

No

Debridement and washout, internal fixation, skin graft

16

Ceftriaxone, metronidazole, gentamicin

Bacillus cereus*

34

Male

Wild saltwater

Crush injury and fractures of upper and lower limbs

Yes

Debridement and washout, tibial nail, joint washout

13

Ceftriaxone, metronidazole, gentamicin

Bacillus cereus*

23

Male

Farmed saltwater

Superficial skin and soft tissue wound of upper limb

No

No surgical intervention

N/A

Ceftriaxone, metronidazole

Staphylococcus aureus

29

Male

Wild saltwater

Fractures of upper and lower limbs

Yes

Multiple debridements and washouts, joint washouts, knee reconstruction

13

Cephazolin, metronidazole, doxycycline

Pseudomonas aeruginosaEnterococcus spp.

N/A = not applicable. * Likely represents colonisation rather than true infection.

Treatment of latent tuberculosis infections in the Darwin region

As it is estimated that one-third of the world population have a latent tuberculosis infection (LTBI), treatment to prevent active tuberculosis is an essential component of the World Health Organization “End TB Strategy”.1

To inform and evaluate practice, we undertook a cohort study of people in the Darwin region (estimated population, 140 000; 25% Indigenous Australians, 25% overseas-born residents) diagnosed with LTBI according to Northern Territory guidelines2 during June 2013 – July 2014. Diagnosis was based on a positive Mantoux test result2 and the absence of radiological and clinical evidence for active tuberculosis. Demographic and treatment acceptance and compliance data were collected from the sole treatment centre serving the region. The recommended therapy was 9 months’ treatment with isoniazid, or 4 months’ treatment with rifampicin if isoniazid was contraindicated.2 Treatment adherence was assessed monthly on the basis of clinic attendance, self-reported adherence, and collection of the medication.

During the study period, 573 people were diagnosed with LTBI, of whom 422 (74%) were overseas-born, 81 (14%) were Indigenous Australians, and 70 (12%) were non-Indigenous Australians. The age range was 0–77 years (median, 32 years); 61% were male. The proportions of people diagnosed with LTBI who were offered, accepted and completed treatment are shown in the Box. Uncertainty on the part of the physician about an individual’s ability to complete treatment was the most common reason for not offering treatment, including to members of transient populations, such as those with short prison sentences and immigration detainees. Most patients who did not complete therapy had been lost to follow-up, either moving interstate (31%) or defaulting without a reason being recorded (25%). Outcome data for people moving interstate were not collected, as there are no mechanisms for routinely sharing such data between Australian states, and forwarding addresses were unavailable. The 55% completion rate therefore probably underestimates the proportion of those who completed treatment.

Parents and guardians of all 28 children under 6 years of age accepted treatment for their children, 12 of whom (43%) completed treatment, including six of 11 who were contacts of people with active tuberculosis, four of 16 immigration detainees, and three of seven refugees. Five children did not, however, commence treatment (three immigration detainees, two refugees), and 11 moved interstate without completing treatment. Nine of those moving interstate were immigration detainees, highlighting the transiency of this population and the uncertainty of outcomes arising from a lack of feedback between states about LTBI treatment compliance.

Indigenous Australians were significantly more likely to accept treatment than overseas-born people (odds ratio [OR], 4.46; 95% CI, 1.55–12.8) or non-Indigenous Australians (OR, 7.69; 95% CI, 2.33–25.4). Overseas-born patients were less likely to complete treatment than Indigenous (OR, 1.34; 95% CI, 0.66–2.72) or non-Indigenous Australians (OR, 1.38; 95% CI, 0.56–3.41). This finding, however, was not statistically significant, and potentially confounded by the fact that all 36 patients who moved interstate were overseas-born, so that completion for this population was possibly higher.

Similar to the findings of other Australian studies, 45% of patients who accepted treatment did not complete it, representing missed opportunities for preventing disease.3,4 Uncertainty about treatment adherence by overseas-born people moving interstate indicates that national data sharing and collaboration between tuberculosis services should be improved. LTBI treatment could then be evaluated according to WHO recommendations, and targeted measures to improve treatment outcomes for this high-risk population implemented.1,3 Further, the reasons for not completing treatment were often unknown; communicating with non-adherent patients would identify problems and enable targeted interventions for improving compliance.

Encouragingly, we found high uptake of treatment by Indigenous Australians, which may help reduce the disproportionately high incidence of active tuberculosis in this population, compared with non-Indigenous Australians.

Box –
The proportions of people diagnosed with latent tuberculosis infection who were offered, accepted and completed treatment, Darwin, June 2013 – July 2014

Total

Age group (years)

0–5

6–15

16–35

> 35

People diagnosed with a latent tuberculosis infection (LTBI)

573

32

56

244

241

Reasons for LTBI screening: asylum seeker/refugee (24%); health care worker (19%); tuberculosis contact (17%); (pre-)immunosuppression (7%); school student (overseas-born) (6%); medical referral (6%); incarcerated (6%); immigration health undertaking (3%); defence force personnel (3%); other (9%)

Offered treatment

374 of 573 (65%)

28 (88%)

48 (86%)

153 (63%)

145 (60%)

Reasons for not offering treatment: short term detention/prison sentence (physician uncertain about future adherence) (37%); low risk (35%); excessive alcohol use or liver disease (6%); prior LTBI treatment (4%); pregnant/lactation (4%); depression (2%); other (14%)

Accepted treatment

265 of 374 (71%)

28 (100%)

38 (79%)

103 (67%)

96 (66%)

Completed treatment

147 of 265 (55%)

12 (43%)

26 (68%)

56 (54%)

53 (55%)

Reasons for incomplete treatment: moved away from treatment centre (31%); no reason given/defaulted (25%); did not commence treatment (20%); elevated liver enzyme levels (5%); peripheral neuropathy (3%); patient died of disease other than tuberculosis (3%); rash (2%); other (12%)

Trends in the prevalence of hepatitis B infection among women giving birth in New South Wales

The known In NSW, HBV vaccination of infants born to women at high risk commenced in 1987, and catch-up vaccination programs for adolescents in 1999. 

The new Among women giving birth, targeted infant and school-based adolescent vaccination programs were associated with an 80% decline in HBV prevalence among Indigenous women by 2012. HBV prevalence in Indigenous women was higher in rural and remote NSW than in major cities, but among non-Indigenous and overseas-born women it was higher in cities. 

The implications HBV prevention programs for Indigenous Australians should focus on regional and remote NSW and those for migrant populations on major cities. Antenatal HBV screening can be used to monitor population HBV prevalence and the impact of vaccination programs. 

Chronic infection with the hepatitis B virus (HBV) can cause serious liver disease, and contributes worldwide to a significant burden of disease. Most chronic infections are acquired early in life, predominantly by maternal transmission.1 While its prevalence in Australia is generally considered to be low (under 2%), the prevalence of HBV infections in Aboriginal and Torres Strait Islander (hereafter: Indigenous)2 people and in some migrant populations3 has been substantial.

A three-dose vaccine that is 95% effective in preventing HBV infection4 has been available in Australia since the early 1980s.5 In New South Wales, a targeted HBV vaccination program commenced in 1987.6 The program offered vaccination for babies born to parents from population groups considered to be at higher risk of HBV infection (defined as HBV prevalence ≥ 5%), including Indigenous Australians.7 In 1997, the National Health and Medical Research Council recommended universal HBV catch-up vaccination of children aged 10–16 years;8 in NSW, this was provided from 1999 to adolescents born since 1983 by general practitioners.9 The National Immunisation Program Schedule included universal infant HBV vaccination from May 2000. During 2004–2013, this was complemented by a NSW-wide school-based HBV vaccination catch-up program for year 7 students (born since 1991; online Appendix 1).5,7 In NSW, coverage through the universal infant program was reported to have exceeded 95% since 2003,10 and about 60% of eligible children not vaccinated as infants had been vaccinated through the school-based catch-up program in 2011 and 2012.11

To assess the impact of the vaccination programs on HBV prevalence in NSW, we determined its prevalence in women giving birth, as in Australia they are routinely screened for HBV during pregnancy.12 Our methodology was similar to that used in earlier studies that linked records of women giving birth and HBV infection notifications.2,3

Methods

Data sources and linkage

Data from two statutory registers were linked. The NSW Perinatal Data Collection (PDC) records all births in NSW of babies of at least 400 grams birth weight or 20 weeks’ gestation. The PDC contains details about the mother, such as year and country of birth, parity, postcode of residence, and Indigenous status, and about the birth, including the date of delivery and outcome. The NSW Notifiable Conditions Information Management System (NCIMS) is a population-based surveillance system that records reports of conditions deemed notifiable under the NSW Public Health Acts 1991 and 2010.13,14 The Act requires notification to NCIMS by any laboratory detecting HBV surface antigen (HBsAg), a marker of HBV infection, in a specimen submitted for diagnostic testing. The NCIMS records personal details, including date of birth, sex, postcode, and classification of the report as newly acquired hepatitis B infection or infection of unspecified duration (based on standard definitions15), notification date, and either the estimated onset date or date of the diagnostic test.

PDC records of women giving birth between January 1994 and December 2012 and NCIMS HBV notifications for the same period were available. Records from the two registers were linked by probabilistic matching of personal identifying details; this was conducted by the NSW Centre for Health Record Linkage (CHeReL), independently of the study investigators, to whom de-identified, linked data were provided for analysis. The reported false positive and negative rates for CHeReL linkage are about 0.5%.16

Study population and definitions

After linkage, we restricted our study population to women resident in NSW — using their postcode on the PDC record — of reproductive age (10–55 years at time of giving birth) who gave birth to their first child (ie, parity null) between January 2000 (when routine antenatal screening for HBV began17) and December 2012.

A woman was defined as having a chronic HBV infection at the delivery of her first child if there was at least one linked HBV notification in the NCIMS database that was recorded as unspecified and with a notification date earlier than the delivery date. Women with no linked HBV notifications were assumed to be not infected with HBV. Women with an HBV infection notified as being acute were excluded from the analysis, as it was unknown whether they would have cleared their acute infection or progressed to a chronic infection.

Statistical analysis

Women were categorised into four groups by their year of birth, which determined the likelihood of their being included in an HBV vaccination program: pre-vaccination era (maternal year of birth, 1981 or earlier); catch-up vaccination, predominantly GP-administered (1982–1987); at-risk newborn vaccination (1988–1991); and universal school-based catch-up and at-risk newborn vaccination (1992–1999; online Appendix 1). No women in our analyses were born during the period of universal HBV vaccination of newborns (from May 2000).

We also classified the women as Indigenous Australian, non-Indigenous Australian-born, or overseas-born women, based on their PDC record. For Indigenous status, we enhanced reporting in the PDC by linkage to other PDC records.18 Records with missing country of birth data (2090 records, 0.4% of all records) were placed in the “born overseas” category.

We calculated crude HBV prevalence for the four maternal year-of-birth categories, and used logistic regression to examine the relationship between these categories and HBV infection. We adjusted analyses for year of giving birth (in 5-year intervals) to account for possible temporal trends in HBV prevalence,2 and for the mother’s area of residence (two categories, based on residential postcode in the PDC record: major cities and regional/remote, according to the Accessibility/Remoteness Index of Australia19), as HBV prevalence in Australia varies between regions.3 The two most recent maternal year-of-birth categories (1988–1991, 1992–1999) were combined (1988–1999) for the logistic regression analysis because the numbers of records in the individual groups were small.

Ethics approval

The study was approved by the NSW Population and Health Services Research Ethics Committee (reference, 2009/11/193) and the Aboriginal Health and Medical Research Council Human Research Ethics Committee (reference, 841/12).

Results

Between January 2000 and December 2012, 482 998 women residing in NSW gave birth to their first child (PDC data); 54 were linked to an acute HBV notification and excluded from further analysis. Of the remaining 482 944 records, 11 738 (2.4%) were Indigenous Australian women, 319 629 (66.2%) were non-Indigenous Australian-born women, and 151 577 (31.4%) were born overseas. A linked unspecified HBV notification before the date of birth of their first child was available for 3383 women (HBV prevalence, 0.70%; 95% confidence interval [CI], 0.68–0.72%). HBV prevalence was estimated as 0.79% (95% CI, 0.63–0.95%) for Indigenous Australian women, 0.11% (95% CI, 0.09–0.12%) for non-Indigenous Australian-born women, and 1.95% (95% CI, 1.88–2.02%) for overseas-born women.

For Indigenous Australian women, the prevalence of HBV infection was significantly lower for those who were eligible for universal school-based or at-risk newborn vaccination (born between 1992 and 1999) than for women born during the pre-vaccination period (≤ 1981): 0.15% (95% CI, 0.00–0.35%) v 1.31% (95% CI, 0.91–1.71%; for trend, P < 0.001). For non-Indigenous Australian-born women, the prevalence also declined, but the fall was not statistically significant: from 0.10% (95% CI, 0.09–0.11%) to 0.04% (95% CI, 0.00–0.09%; for trend, P = 0.5). There was no significant trend for overseas-born women between the two periods (P = 0.1) (Box 1, online Appendix 2).

In analyses adjusted for year of giving birth and region of residence (Box 2), the proportion of Indigenous Australian women notified as having an HBV infection was 80% lower for those eligible for vaccination as part of the at-risk infant or universal school-based vaccination programs (born 1988–1999) than for women born during the pre-vaccination period (1981 or earlier) (adjusted odds ratio [aOR], 0.20; 95% CI, 0.09–0.48). There was no significant change for non-Indigenous Australian-born women (aOR, 0.87; 95% CI, 0.54–1.44). For overseas-born women, the number of notifications was significantly higher for women born during 1988–1999 than for those born before 1981 (aOR, 1.38; 95% CI, 1.15–1.67).

Box 2 also shows that HBV notifications were more frequent for Indigenous women living in regional and remote areas than for those in major cities (aOR, 2.23; 95% CI, 1.40–3.57). The opposite applied to non-Indigenous Australian-born (aOR, 0.39, 95% CI, 0.28–0.55) and overseas-born women (aOR, 0.61; 95% CI, 0.49–0.77).

The study timeframe and inclusion criteria (first births during 2000–2012) meant that the mean age of mothers was lower in later than in earlier birth year groups. After adjusting for maternal birth year groups, a significant decline in HBV notifications among Indigenous women of about 30% was still detected (aOR for each 5-year period, 0.69; 95% CI, 0.49–0.97; P = 0.03). A decline for overseas-born women was also found, but it was much smaller (aOR, 0.89; 95% CI, 0.84–0.93; P < 0.001), and there was no change for non-Indigenous Australian-born women (aOR, 0.99; 95% CI, 0.84–1.16; P = 0.90; Box 2).

To further explore the changes in HBV prevalence in overseas-born women, HBV notifications were also analysed by maternal year of birth and region of birth (Box 3). The highest proportions of women with HBV notifications were for those born in North-East Asia, South-East Asia, and sub-Saharan Africa. The small sample sizes made comparisons of trends across maternal year of birth less robust, but a consistent increase in HBV notification rates was observed for women born in North-East Asia and sub-Saharan Africa (for each trend, P < 0.001).

Discussion

This is the largest study to examine differences in HBV notification rates for women born before and after the introduction of HBV vaccination programs in Australia, analysed by country of birth, Indigenous status, and region of residence. We found that HBV notification rates for Indigenous women born after the introduction of targeted infant HBV vaccination were 80% lower than for those born earlier. For non-Indigenous Australian-born and overseas-born women there were no consistent associations between HBV notification rates and HBV vaccination programs in NSW. Despite limited data about the level of HBV vaccination coverage achieved when the at-risk newborn vaccination program was introduced in NSW in 1987, our findings suggest that it was highly successful. The estimates of HBV notification rates in Indigenous women were substantially lower among those born after 1987 than among women born before the start of the program (Box 1). It is notable that the 80% decline we report matches the 79% reduction found by a study that compared Indigenous women in the Northern Territory born before and after the introduction of universal newborn vaccination,2 suggesting that the targeted program was highly effective in reaching those at risk. The estimated fall is also similar to the results of investigations in other countries of the impact of universal newborn vaccination programs.20,21

A lack of consistent trend in HBV notifications among non-Indigenous Australian-born women might be expected, as the notification rate in this population before the introduction of vaccination was considerably lower than for Indigenous women. Further, most non-Indigenous women born during 1988–1999 would have been eligible only for school-based catch-up vaccination, which is less effective in preventing chronic disease than infant vaccination. Interpreting the relationship between birth cohorts and HBV prevalence in overseas-born women was complicated by a number of factors, including the differing prevalence of HBV in the regions from which overseas-born women migrated, their age at migration, and the lack of information about receipt of vaccination in their country of origin. When analysed by region of origin, the observed changes in notification rates could reflect either varying local uptake of infant HBV vaccination or differences in the populations that have migrated to Australia from particular regions over the 13-year study period. The smaller numbers of women involved in each group, however, limit our ability to draw conclusions.

Regional differences in HBV prevalence were also observed. Indigenous Australian women in regional and remote NSW were more likely to be HBV-seropositive than those in urban areas, whereas the reverse was true for non-Indigenous Australian-born and overseas-born women. These differences in HBV prevalence have been described previously in Indigenous Australians,2 but the reasons underlying them are unclear. The colonisation process and the institutional racial discrimination that Indigenous Australians experience affect their health outcomes, mediated by a number of different pathways, including unequal access to health care, housing and employment.22,23 As access to primary health care services relative to need is lowest in remote areas, and proportionately more Indigenous than non-Indigenous Australians live in remote areas,24 these factors may contribute to higher HBV prevalence among Indigenous women in rural and remote areas. In addition, an uncommon, more virulent HBV subgenotype circulates among Indigenous Australians in the NT, perhaps reducing the efficacy of vaccination;25 the distribution of this subgenotype in NSW, however, is unknown.

The higher prevalence of HBV among urban than regional non-Indigenous women may be related to the higher proportions of women in cities who inject drugs or are in prison, both risk factors for acute HBV infection.26 For women born overseas, the difference might be related to the fact that a greater proportion of migrants from high HBV prevalence countries (such as Asia) reside in urban than in regional and remote areas (online Appendix 3).27

It was not possible in our ecological study to take into account interactions between the effects of age and calendar year on HBV notification. Women who were born more recently, and therefore more likely to have been vaccinated, would have been younger at the time of our linkage, but also potentially subject to different risks of exposure at a given age. Including the year a woman gave birth as a factor in the regression model for Indigenous Australian women led to a small reduction in the effect of maternal birth year on HBV prevalence, and HBV prevalence was lower for more recent year of giving birth, after adjusting for maternal year of birth (Box 2). This suggests that temporal trends other than the effect of maternal birth year may have contributed to the decline in HBV notifications for Indigenous Australian women, although residual confounding related to inadequate adjustment for maternal birth year effects cannot be excluded. A similar trend, but of smaller magnitude, was seen among overseas-born women.

Antenatal screening for HBV infection enabled us to systematically assess HBV prevalence in a large population of women. Study limitations include our focus on women giving birth; our conclusions may not be generalisable to other women or to men, but we expect that the overall trends would be similar. We were unable to assess the impact of universal newborn vaccination on HBV notifications, as no women born after 2000 had given birth during the study period. Further, the ecological nature of our analyses depended on assumptions about the exposure of individuals to different vaccination strategies according to year of birth, whereas individual level vaccination data would assist us more reliably quantify their effects. Interpreting changes in HBV prevalence by country or region of birth was further limited by a lack of information about when women migrated to Australia. Some HBV notifications classified as “unspecified” may actually have been acute infections, but their frequency should not have differed between maternal birth year groups, and would therefore not have affected our estimates of HBV prevalence. Finally, linkage errors are possible, but their rate is known to be low.

Conclusion

Analysing routine antenatal HBV screening data is a simple and cost-effective method for monitoring changes in HBV prevalence in both the general population and in some high risk populations. The newborn and childhood HBV vaccination programs in NSW have had a significant impact on HBV prevalence in Indigenous Australian women, but it is still substantially higher than among non-Indigenous women. HBV infection prevention programs for high risk groups should be targeted differently, with those for Indigenous Australians focused on regional and remote NSW, and those for migrant populations on major cities. Finally, our analysis could be repeated periodically to assess the ongoing impact of universal newborn HBV vaccination and future targeted programs on HBV prevalence in Australia.

Box 1 –
Hepatitis B notifications for primiparous women giving birth, by maternal birth year, New South Wales, 2000–2012

* HBV notification rates plotted against the median maternal year of birth for each maternal year of birth category (≤ 1981, 1982–1987, 1988–1991, 1992–1999).

Box 2 –
Association between HBV notifications* and maternal year of birth, year of giving birth, and region of residence

Median age (years)

Number of women

Univariate analysis

Multivariate analysis

Giving birth

Giving birth, with HBV record

Odds ratio (95% CI)

P†

Adjusted odds ratio (95% CI)‡

P†

Australian-born women, Indigenous

Maternal year of birth

≤ 1981

27.4

3057

40 (1.3%)

1

< 0.001

1

0.002

1982–1987

20.8

4509

45 (1.0%)

0.76 (0.50–1.17)

0.79 (0.51–1.23)

1988–1999

18.8

4172

8 (0.2%)

0.15 (0.07–0.31)

0.20 (0.09–0.48)

Region of residence

Major cities

4916

24 (0.5%)

1

0.002

1

< 0.001

Regional/remote

6752

69 (1.0%)

2.08 (1.31–3.32)

2.23 (1.40–3.57)

Year of giving birth (per 5 years)

0.45 (0.34–0.61)

0.69 (0.49–0.97)

0.03

Australian-born women, non-Indigenous

Maternal year of birth

≤ 1981

30.7

227 608

227 (0.1%)

1

0.50

1

0.10

1982–1987

23.6

67 762

91 (0.1%)

1.35 (1.06–1.72)

1.47 (1.14–1.91)

1988–1999

19.9

24 259

18 (0.1%)

0.74 (0.46–1.20)

0.87 (0.54–1.44)

Region of residence

Major cities

242 392

298 (0.1%)

1

< 0.001

1

< 0.001

Regional/remote

77 195

38 (0.0%)

0.40 (0.29–0.56)

0.39 (0.28–0.55)

Year of giving birth (per 5 years)

1.04 (0.90–1.20)

0.99 (0.84–1.16)

0.90

Overseas-born women

Maternal year of birth

≤ 1981

31.7

116 659

2245 (1.9%)

1

0.10

1

0.001

1982–1987

25.2

29 431

580 (2.0%)

1.03 (0.93–1.12)

1.11 (1.01–1.22)

1988–1999

20.9

5487

129 (2.4%)

1.23 (1.03–1.47)

1.38 (1.15–1.67)

Region of residence

Major cities

144 926

2872 (2.0%)

1

< 0.001

1

< 0.001

Regional/remote

6621

82 (1.2%)

0.62 (0.50–0.77)

0.61 (0.49–0.77)

Year of giving birth (per 5 years)

0.92 (0.88–0.96)

0.89 (0.84–0.93)

< 0.001

* For the purposes of our analysis: defined as a record in the NSW Notifiable Conditions Information Management System of the detection of hepatitis B surface antigen (HBsAg) between January 1994 and December 2012 with the infection classified as being of unspecified duration (or not newly acquired). † For trend across categories of maternal birth year, calculated using the median maternal year of birth in each category. ‡ Adjusted for maternal year of birth, region of residence, and year of giving birth (5-year intervals).

Box 3 –
HBV notifications for non-Australian-born women giving birth for the first time, by region of birth

Mother’s region of birth

Maternal year of birth

≤ 1981

1982–1987

1988–1999

Number of women

Proportion with HBV record (95% CI)

Number of women

Proportion with HBV record (95% CI)

Number of women

Proportion with HBV record (95% CI)

North-East Asia

21 159

4.4% (4.2–4.7%)

4455

5.4% (4.7–6.1%)

583

11.2% (8.8–14.0%)

South-East Asia

22 824

4.3% (4.2–4.7%)

4596

4.5% (4.0–5.2%)

680

4.1% (2.9–5.9%)

Oceania (excluding Australia)

12 124

1.1% (0.9–1.2%)

3335

1.0% (0.7–1.4%)

1260

0.7% (0.4–1.4%)

Sub-Saharan Africa

4409

0.9% (0.6–1.2%)

965

3.0% (2.1–4.3%)

244

4.9% (2.8–8.4%)

North Africa or Middle East

9064

0.6% (0.5–0.8%)

4592

0.5% (0.3–0.8%)

1368

0.9% (0.5–1.5%)

South or Central Asia

12 268

0.3% (0.3–0.5%)

7292

0.4% (0.3–0.6%)

831

0.2% (0.1–0.9%)

Europe

25 899

0.2% (0.1–0.2%)

2764

0.4% (0.3–0.8%)

303

0.3% (0.1–1.9%)

Americas

7262

0.04% (0.0–0.1%)

1084

0.3% (0.1–0.8%)

126

0.0% (0.0–3.0%)

Other

1650

0.6% (0.3–1.0%)

348

0.9% (0.3–2.5%)

92

0.0% (0.0–4.0%)

Dengue and travellers: implications for doctors in Australia

Awareness of the problem is the first step towards control

The study by Tai and colleagues reported in this issue of the MJA highlights the risk of dengue in Australia posed by the endemic Aedes aegypti and A. albopictus vectors, together with increasing travel by Australians to dengue-endemic destinations.1 From 1991 to 2012, most cases of notified dengue in Australia were related to overseas travel, with respective increases in 2010 and 2011 of 298% and 155% above the 5-year mean notification rate; the risk of dengue in travellers returning from Indonesia between 2000 and 2011 was 8.3 times that for travellers returning from all other destinations.2 The global trade in used tyres (believed to facilitate the distribution of eggs and immature forms of mosquito vectors), rapid urbanisation in Asia and Latin America, more frequent international travel, and ineffective vector control have each contributed to the increasing global prevalence of dengue.3 It is pertinent to consider the threat of dengue in Australia with respect to travel and climatic factors.

During 1993–2005, a decrease in the average Southern Oscillation Index (that is, warmer conditions) over the preceding 3–12 months was significantly associated with increasing monthly numbers of dengue cases in Queensland.4 Sequencing data for dengue virus envelope protein genes in symptomatic travellers returning to Queensland during 2002–2010 indicated that there was an elevated risk of imported dengue associated with travel to Asia and Papua New Guinea.5

The impact of socio-ecological factors on local and imported cases of dengue should also be evaluated. A study in Queensland during 2002–2005 found that the number of patients with locally acquired dengue increased by 6% for each 1 mm increase in average monthly rainfall and by 61% for each 1°C increase in monthly maximum temperature; for imported dengue, the increase was by 1% per 1 mm increase in average monthly rainfall and 1% per single unit increase in average socio-economic index.6 A study in Cairns, 2000–2009, found that the monthly incidence of locally acquired dengue was significantly positively correlated with the monthly number of imported cases, as well as with monthly minimum temperature, monthly relative humidity, and standard deviation of daily relative humidity; it was negatively linked with monthly rainfall levels.7

However, other factors determine the risk of dengue in Australia, including human behaviour. Increased use of water storage tanks in response to drought conditions has increased the geographic distribution of A. aegypti beyond the expansion attributable to climate change.8 A dynamic life table simulation model that assessed the impact of climate change on A. aegypti distribution, based on current (1991–2011) and future (2046–2065) climate scenarios, predicted decreasing mosquito numbers in a scenario that included increasing atmospheric carbon dioxide levels and higher global temperature, but increasing mosquito abundance with more moderate increases in global carbon dioxide and temperature levels. The body weight of A. aegypti and the extrinsic incubation period of the dengue virus (ie, period between infection of the mosquito and its ability to transmit the virus) were reduced in both scenarios, and the rate of mosquito eggs deposition increased.9 Nevertheless, the probability of dengue in Australia outside northern Queensland is low according to a formal modelling framework that took into account the current distribution of dengue, rainfall, temperature, and urbanisation.10

In the absence of highly effective dengue vaccines and effective therapeutics, three elements of the global strategy for dengue prevention and control should be emphasised: surveillance for planning and response; reducing the disease burden; and changing behaviour to improve vector control.11 Dengue virus surveillance has helped mitigate dengue outbreaks in Singapore by providing early warning of impending outbreaks, allowing time to intensify vector control.12 Chemical control with larvicides and adulticide surface sprays in water stored for domestic use, and biological control agents such as larvivorous fish can be useful. Environmental management strategies include source reduction, clean-up campaigns, regular water container emptying in households and public spaces, installation of water supply systems, solid waste disposal management, and appropriate urban planning, all aimed at reducing A. aegypti breeding levels. Finally, social mobilisation through public education may enhance the effectiveness of vector control strategies.11 Promising future strategies include the introduction of genetically modified male mosquitoes that sterilise wild-type female mosquitoes, and of Wolbachia-infected A. aegypti, which are resistant to dengue infection.3

Doctors in Australia must be alert to the possibility of dengue in their differential diagnosis of febrile conditions in returned travellers. Referral for specialist opinion and confirmation of dengue virus infection by rapid diagnostic tests, such as non-structural antigen 1 assay, are appropriate when there is doubt about the diagnosis.11 Triage for admission to hospital should be based on the World Health Organization dengue guidelines,13 with particular attention to the warning signs of severe dengue. These signs were recorded for 40% of patients in the study by Tai and colleagues.1 Education of hospital doctors about these guidelines may well be needed, as the study also found that a strict fluid balance chart was not kept for 86% of the patients diagnosed and treated for dengue, 27% of patients received probably unnecessary antibiotics and blood products were administered to 15%, and potentially harmful non-steroidal anti-inflammatory drugs were prescribed for 22%.1

Death from an untreatable infection may signal the start of the post-antibiotic era

The ASID perspective on the most important infectious diseases problem of 2017 and beyond

On 12 January 2017, the United States Centers for Disease Control and Prevention reported that a woman in Nevada had died from an untreatable Gram-negative infection resistant to all available classes of antibiotics.1 The woman had sustained a fractured femur, complicated by osteomyelitis, while travelling in India, necessitating hospitalisation and intravenous antibiotic treatment. After returning to the US in mid-2016, she was admitted to hospital with systemic inflammatory response syndrome, probably secondary to a hip seroma that developed after the earlier surgery, and a pan-resistant Klebsiella pneumoniae was isolated from a tissue specimen; the woman died of untreatable septic shock.

Although infections by antimicrobial-resistant organisms are now common, we and other infectious diseases physicians, microbiologists, and public health experts in Australia and around the world are deeply alarmed by this report, as it may herald a post-antibiotic era in which high level antimicrobial resistance (AMR) is widespread, meaning that common pathogens will be untreatable. Should this be the case, it would profoundly affect all areas of health care, and society. Simple childhood infections would once again be life-threatening events, major surgery would be associated with high mortality, chemotherapy for cancer and organ transplantation would no longer be possible.

There is increasing international recognition that AMR is one of the major public health problems of our time. An independent review of AMR prepared for the United Kingdom government recommended a global public awareness campaign, reducing unnecessary antibiotic use in agriculture, and providing incentives for both AMR diagnostics and new drug development.2 The authors of the report emphasised that these goals could not be achieved without the concerted participation of the United Nations and G20 group. In September 2016, the G20 declared AMR a serious threat to public health, economic growth, and global economic stability, and called for prudent antibiotic use and action to tackle AMR.3 The UN General Assembly held a special summit later the same month at which several countries affirmed national action plans for dealing with AMR.4

The Australian government has been proactive in its response to AMR, promptly forming the Australian Antimicrobial Resistance Prevention and Containment Steering Group, led by the secretaries of the federal Departments of Health and Agriculture. Australia’s first National Antimicrobial Resistance strategy was released in June 2015, supporting a “One Health” approach to mitigating AMR (that is, recognising that human, animal and environmental health are interrelated),5 and was soon followed by an implementation plan.6 Our challenge is to translate this plan “into swift, effective, life-saving actions across the human, animal and environmental health sectors”, as the Director-General of the World Health Organization, Margaret Chan, has urged.4

The per capita consumption of antibiotics by people in Australia is among the highest in the world.7 Australian prescribers and consumers need to reduce antibiotic use in both humans and animals. The National Health and Medical Research Council National Centre for Antimicrobial Stewardship is leading national initiatives to adapt human antimicrobial stewardship to busy clinical practices in both the hospital and community settings, with the aim of improving prescribing behaviour.8 The Royal Australasian College of Physicians and the Australasian Society for Infectious Diseases (ASID) have recently developed a list of the top five low value interventions in infectious diseases,9 as discussed by Spelman and colleagues in this issue.10 Four of the five recommendations are related to reducing antibiotic use in settings where they are of limited value: asymptomatic bacteriuria, leg ulcers without clinical infection, upper respiratory tract infections, and treating faecal pathogens in the absence of diarrhoea.9 The Australian Veterinary Association has released guidelines for the prescribing of veterinary antibiotics, but antimicrobial stewardship in animals and agriculture is yet to be established.11

To have an impact on AMR, we will need to address all its drivers in Australia, including unrestrained use of antibiotics and poor infection control in both humans and animals, the decline of antibiotic research and development, and the introduction of AMR by ingesting imported food products (eg, seafood and meat) that contain AMR organisms, particularly if antibiotics were employed during their production, and through international travel. Coordination of these actions will be critical, but also complex in Australia, as health departments, antimicrobial prescribing, and communicable diseases surveillance are regulated by state-based authorities, while the federal government regulates quarantine, biosecurity, and the licensing and subsidising of medicines. The Australian Medical Association has recently called for immediate establishment of an Australian National Centre for Disease Control, “with a national focus on current and emerging communicable disease threats, engaging in global health surveillance, health security, epidemiology and research”.12 Such a body could operate in a similar manner to the European Centre for Disease Prevention and Control (ECDC), complementing and coordinating existing state- and territory-based activities.

The recent death from an untreatable infection in Nevada provides a preview of a future without effective antibiotics. A list of tangible actions against each of the drivers of AMR, coordinated across human and animal health and agriculture, must be an urgent priority. ASID, the Australian Society for Antimicrobials, and animal health societies will host government representatives and stakeholders in June 2017 at the second Australian AMR Summit in Melbourne, with the aim of drafting this action list.

Impact of overweight and obesity as a risk factor for chronic conditions

This report updates and extends estimates of the burden due to overweight and obesity reported in the Australian Burden of Disease Study 2011 to include burden in people aged under 25, revised diseases linked to overweight and obesity based on the latest evidence, and estimates by socioeconomic group. The report includes scenario modelling, undertaken to assess the potential impact on future health burden if overweight and obesity in the population continues to rise or is reduced. The enhanced analysis in the report shows that 7.0% of the total health burden in Australia in 2011 is due to overweight and obesity, and that this burden increased with increasing level of socioeconomic disadvantage.

JOSEPH PRIESTLEY AND A BOTTLE OF POP

PROFESSOR STEPHEN LEEDER, EMERITUS PROFESSOR PUBLIC HEALTH, UNIVERSITY OF SYDNEY

A South African friend, passionate about finding effective ways of combatting obesity worldwide, recently sent me a clipping from The Yorkshire Evening Post of March 22, titled ‘How fizzy drinks were invented in Leeds on this day 250 years ago’. 

The inventor was Joseph Priestley, the quirky theologian and polymath who had discovered oxygen years earlier. 

Priestley came to live next door to a Leeds brewery, in which he took an inquisitive interest. He found that the gas given off by fermenting beer, which he called ‘fixed air’ to distinguish it from ordinary air, while toxic to mice, could be dissolved in water, giving it an agreeable flavour. He served the water to his friends, who liked it. And then, in the late eighteenth century, the Swiss J J Schweppe developed a large-scale process to carbonate water.

Today our concern with fizzy drinks is mainly with their huge sugar content and sugar’s contribution, the world over, to weight gain. With several countries introducing a sugar tax, such a tax is being considered here.

But as Linda Cobiac, King Tam, Lenner Veeman and Tony Blakely wrote in a paper in PLOS Medicine recently, ‘the cost-effectiveness of combining taxes on unhealthy foods and subsidies on healthy foods is not well understood’. Cobiac and colleagues are public health and health policy professionals in Melbourne, Brisbane, and Wellington, NZ.

They have developed a complex model of prices, relationships of salt, fat, sugar and fresh vegetables to disease states, and have used data from several countries about what could be achieved by taxing or subsidising certain foods.

Their simulations showed that ‘the combination of taxes and subsidy could avert as many as 470,000 disability-adjusted life years (that is, loss of life due to premature death and discounted years due to illness) in Australia’s 22 million people with a net saving [yes, a SAVING!] of $3.4 billion a year’.

I have a message for those who tell us that the costs of health care in Australia are unsustainable. If you want to save money, here are some approaches that could be tried – and confirmed or refuted by experimentation. This is an important caveat given that models are not the same as RCTs.

But this experimentation is surely better than trying to save health dollars by coordinating care, for patients with serious and continuing illness, between hospital and home – a demonstrably worthwhile thing to do – but which, because of the needs it uncovers, inevitably ends up costing more than standard fragmented care.

The authors draw a quiet and modest conclusion. “With potentially large health benefits for the Australian population and large benefits reducing health sector spending on the treatment of non-communicable diseases, the formulation of a tax and subsidy package should be given a more prominent role in Australia’s public health strategy.”

Their approach might seem unorthodox, but I can imagine that Priestley, the radical preacher, might be supportive. His beliefs cost him a berth as science adviser on Cook’s second voyage. He and his family, by fleeing to Pennsylvania, only just escaped death for their unorthodox theology. 

He was a critical thinker and explorer.  I fancy that, were he with us today, he might have encouraged us to try this out.