2015 3 s Newsletter

Maternal GBS detection 3 New genetics technology 4 SA Pathology Inside in the new RAH 5 Haemoglobinopathy 6 Vitamin B12 deficiency 8 Aspergillosis 10 Respiratory virus update 12

Wallaroo Mt Gambier > 54 Port Augusta > 59 YEARS > 45 YEARS YEARS Berri > 46 We’re part of YEARS your community Gawler Port Pirie > 35 Murray Bridge YEARS > 29 YEARS > 41 YEARS Victor Harbor Whyalla > 27 Port Lincoln > 50 YEARS > 47 YEARS YEARS

For our patients and our population www.sapathology.sa.gov.au TFT or TSH From the When considering thyroid testing consider whether you should request inside a TFT or a TSH? A request for TFT allows us to robotics technology, which will all provide you with a fT4 test where From the Executive Director work together with the new patient the TSH is abnormal or the tests are administration system (EPAS) being performed: introduced across our SA hospitals. n for the purpose of monitoring The convergence and integration of thyroid disease in the patient; or technologies puts us under pressure n to investigate the sick euthyroid to achieve time lines and agreed syndrome if the patient is an service benchmarks, but also presents admitted patient; or opportunities to embrace change for n to investigate dementia or better patient outcomes. psychiatric illness of the patient; We now have a chance to improve on or the best diagnostic support for all South n to investigate amenorrhoea or Australians, ensuring we are there at the infertility of the patient; or right time for the right clinical reason, n you suspect your patient has a and to support healthcare professionals pituitary dysfunction or making their decisions and tasks easier, n your patient is on drugs that resulting in improved care for our interfere with thyroid hormone few businesses today are patients and the population. unaffected by technological change; metabolism or function. and this will be keenly felt in health. Far from altering our vision, these SA Pathology in particular is in the changes mean we confirm our Please include the relevant clinical process of radical change, which is both commitment to enhanced healthcare notes on your request form. daunting and exciting as significant using tomorrow’s tools, including genetic change like this occurs once every few testing and sequencing for personalised DHEA or DHEA-S generations. care, and in partnerships which will Testing DHEA or its sulphated improve delivery of quality pathology analogue DHEA-S is conducted to I consider myself privileged to be here services to clinicians. at this point in time, as we step into a assess adrenal gland function in new future as part of a wider healthcare SA Pathology is investing in the future a variety of conditions including revolution. and we will be there to take our place hirsutism in women, adrenal in the new RAH as it starts to support dysfunction and the investigation At SA Pathology we are implementing patients, clinicians and our other of adrenal tumours. DHEA-S is more a new electronic pathology laboratory hospitals across the state. stable than DHEA and can be used information system (EPLIS), and are interchangeably with DHEA for most about to implement a new track and Mr Ken Barr clinical situations.

SA Pathology provides routine SA Pathology on mobile DHEA-S testing for screening which is covered under the MBS. DHEA Have you used your mobile phone or tablet to visit the screening is not covered under the SA Pathology web site lately? If you’re looking for a test in the MBS and will attract an upfront Pathology Guide or for a nearby Patient Centre you’ll find the patient fee of $28.23. site much easier to navigate following our recent upgrade for mobile devices. Visit www.sapathology.sa.gov.au next time Unless specifically noted all DHEA you need to know. screening requests will be processed as DHEA-S. ¥ SA Pathology Newsletter Photography Cover Published by SA Pathology SA Pathology Photo and Imaging Our history in regional Editorial Committee Design . Mark Fitz-Gerald, Dianne Zurcher, Sue Dyer Design ISSN 2203 – 2339 Print Kieran Weir and Adrian Griffiths Printing ISSN 2203 – 2347 Online Contact Newstyle Printing [email protected]

SA Pathology Newsletter > 3 – 2015 PAGE 2 Improved detection of maternal GBS On 6th October we replaced the current culture test for Group B Streptococcus (GBS) with a Nucleic Acid Test (NAT) which detects up to 10% more GBS than traditional culture.

What to collect Why change? n Vaginal, rectal and combined swabs Two thirds of neonatal GBS infections penicillin/amoxycillin during labour, if are suitable. occur in mothers who tested negative GBS is detected. Susceptibility testing n Place swabs in liquid Amies and for GBS before delivery. Current is only required for patients with request GBS NAT screen. laboratory methods lack sensitivity severe and immediate IgE-mediated for GBS detection, resulting in a risk allergy such as anaphylaxis – please If additional bacteriological testing is to some infants. GBS NAT, a more indicate this on the request form. required (e.g. because of premature sensitive test, will improve detection rupture of membranes, maternal and reduce infection in newborn Further information fever) the same swab can be used but children. For further information please contact please also; the On Call Microbiologist on Sensitivity testing n request MCS and (08) 8222 3000. ¥ n include clinical information. Prevention of perinatal GBS infection involves administration of IV benzyl-

Sterilising equipment safety SA Pathology’s Food and gas plasma and ozone sterilisation Environmental Laboratory offers rapid processes. We have recently upgraded biological indicators (RBI’s) to monitor our test to provide faster results, in steam units and autoclaves, providing most cases next day. evidence of the proper operation of sterilisation equipment. If you own or operate sterilisation equipment we can help provide the Self-contained RBI’s contain confidence you need to ensure its bacterial spores resistant to the safe operation. mode of sterilisation being measured. Geobacillus stearothermophilus For more information visit is the highly-resistant spore used www.sapathology.sa.gov.au/foodlab or to monitor steam, hydrogen peroxide phone the laboratory on 8222 3363. ¥

New Patient Centres North Kensington Park Angaston Recently relocated to Specialises in paediatrics 3 – 7 Fife Street, Angaston 55 O’Connell Street 360 Magill Road, Kensington Park Monday to Friday 8:00am to 12:30pm Monday to Friday 7:30am to 4:30pm Monday, Tuesday and Thursday Saturday 8:30am to 11:30am Saturday 8:00am to 12 noon 8:30am to 12.30pm SA Pathology Patient Centre hours are Maitland Yorketown correct at time of publication. 69 Robert Street, Maitland 23 Waterloo Bay Road Monday to Friday 8:30am to 12 noon Monday to Friday 8:30am to 11:30am Please check the website Modbury Rose Park for the latest updates Modbury GP Plus 24 Kensington Road, Rose Park www.sapathology.sa.gov.au 77 Smart Road, Modbury Monday, Wednesday & Thursday Monday to Friday 8:30am to 12:30pm 8:30am to 12:30pm

SA Pathology Newsletter > 3 – 2015 PAGE 3 www.sapathology.sa.gov.au > >

New genetics technology> improves diagnosis > >

A significant number of us will be affected by genetically determined diseases in our lives. 2 to 3% of the population will be identified at birth and, by the age of 25, up to 5.5% of the population will have developed a genetic disorder. Later in life, up to 60% of the population is affected by a condition such as cardiovascular disease or cancer in which genetics plays a role.

The diagnostic challenge This unprecedented change in Whole-exome sequencing processing capacity has resulted SA Pathology has effectively applied Diagnosis of genetic disorders has, in significant advances in genetic whole-exome sequencing to severe to date, been hampered by a number pathology. All candidate genes can paediatric cases including multiple of factors leading to some families now be tested at once, significantly congenital abnormalities, complex experiencing years of delay in reducing the time to diagnosis. neurological and metabolic disorders, diagnosis, the so-called ‘diagnostic Depending on the clinical phenotype, developmental delay and intellectual odyssey’. There are literally gene analysis can be broad, disability. thousands of rare genetic disorders, eliminating the need for health each individually affecting only a professionals to prioritise a select While many rare genetic conditions small number of people. This means group of genes for testing. This is a don’t have an effective treatment or that genetics health professionals paradigm shift as, for the first time, cure, it is often possible to alleviate may see few or even no cases of genetic testing may precede early symptoms with new therapies and some conditions in their working attempts at clinical diagnosis. help people better manage their life. A second major challenge has disorders. Test results provide been the vast number of genes Diagnostic testing information on risk of recurrence potentially involved in a given in families and can help plan future condition. This often results in the Targeted testing pregnancies. But for genetically need for consecutive rounds of gene SA Pathology is also accredited for complex conditions, testing the whole prioritisation and testing, each time targeted gene panel analysis using exome is appropriate as it avoids excluding another possible cause. NGS. For conditions with few genetic the problem of prioritising individual causes, testing a subset of genes or gene targets, and repeat testing if the ‘panels’ is appropriate, as only the Next-Generation Sequencing results are negative. genes known to be associated with Advances in sequencing technology a disorder need be tested. are now transforming the way Past obstacles, new breakthroughs genetic disorders are diagnosed. In the past, challenges for genetic We offer targeted gene panel testing Next-Generation Sequencing (NGS) diagnosis included the turnaround for a number of defined disease describes the process by which DNA time, high cost and the anxiety for phenotypes, including familial cancer, is fragmented, selectively targeted patients and families seeking quick cardiomyopathy and inborn errors of and sequenced in a massively parallel answers to complex diagnostic metabolism. fashion, producing millions of short questions. fragments which are then reassembled to identify variants in a patient’s DNA. The technology breakthrough is the ability to scale this process, so that Genetic testing may now a full human exome, the full coding sequence of a patient’s DNA, can be precede early attempts at sequenced in a single run at a cost comparable to that of testing a single gene using traditional technology. clinical diagnosis

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With NGS, genetic tests can take months, not years, and reduce patient uncertainty as the diagnostic detection rate is much higher than that of traditional testing. With an average 20% increase in genetic tests requests per year, investment in technology and improving throughput SA Pathology has been crucial to meeting clinical need. It also ensures that testing remains accessible to all patients in in the new RAH need. SA Pathology’s integration into the new Collaborative research represents generational change that will have significant benefits for patients and health professionals alike. SA Pathology is the first laboratory in Australia to receive NATA Not since 1954, when our laboratory This places SA Pathology operations accreditation for whole-exome functions were extended at the Queen at the epicentre of hospital activity sequencing. This achievement Elizabeth Hospital and established and highlights the critical role resulted from intense collaboration in Mount Gambier and other regional pathology plays in fast diagnosis by scientists, technology experts, centres, has the expansion of and timely treatment. The synergy bio-informaticians, pathologists and services been so important for our between co-located pathology geneticists, together with research patients and the South Australian and hospital personnel, allied staff from the Centre for Cancer population. with fully integrated analysers and Biology (CCB) including the CCB’s interconnected information systems, ACRF (Australian Cancer Research SA Pathology’s operations will be will provide a collaborative patient Foundation Cancer Genomics fully assimilated into the patient care focused service that can supply Facility), UniSA and Adelaide facilities of the new RAH. Allocated rapid answers to demanding clinical University. Support for these activities 3,500 square metres of laboratory questions. came from eResearchSA and grants space on Level 3, we will move most from the ACRF and Therapeutic of our critical patient care tests to SA Pathology has embraced the Innovation Australia (TIA). the new site, with features including opportunity to be part of South leading-edge laboratory information Australia’s major future health Referral systems, automated specimen tracks initiative. and robotic technology. Referral for genetic testing is mainly via clinical geneticists, with other Easily accessed, SA Pathology is medical specialists increasingly located at street level, immediately requesting access to testing. Given to the left of the hospital’s main the potential impact of genetic test entrance. Centrally positioned in results on other family members we the heart of the new hospital, our recommend referral to SA Pathology’s laboratories sit directly below the South Australian Clinical Genetics array of technical suites (operating Service at the Women’s and Children’s theatres) and close to lifts where Hospital in the first instance.¥ priority airlifted patients will be brought into specialist treatment Senior staff at an early planning session for areas. SA Pathology’s new RAH laboratories

SA Pathology Newsletter > 3 – 2015 PAGE 5 www.sapathology.sa.gov.au

Haemoglobinopathy

Adrian Griffiths on the increase? In South Australia in the 60s, 70s and 80s haemoglobinopathy (thalassaemia or variant haemoglobins) was predominantly a condition associated with people of Greek or Italian origin. Awareness in these communities of the risk of having an affected child (and appropriate prenatal testing) resulted in a dramatic reduction in children being born with more severe forms of haemoglobinopathy.

In recent times, due to increasing Laboratory testing Usually the red cell parameters are immigration of other ethnic groups, normal for patients with sickle trait Complete blood examination (CBE) there has been a re-emergence of and in some cases with sickle disease, The marker of most interest to the more severe forms. In 2008 the however, sickle cells may be observed the laboratory, when considering World Health Organisation in its on the blood film. thalassaemia, is the mean corpuscular bulletin “Global epidemiology of haemoglobin (MCH). Generally haemoglobin disorders and derived Haemoglobin studies thalassaemia is associated with a service indicators” estimated SA Pathology currently uses High low MCH and often, but not always, that in Australia and New Zealand Performance Liquid Chromatography a low mean corpuscular volume the number of pregnancies at risk (HPLC) to detect and quantify normal (microcytosis). The mean corpuscular of disease was 351 per annum, and variant forms of haemoglobin. haemoglobin concentration (MCHC), (approximately 20 in South Australia). Total haemoglobin consists of three is an indicator of hypochromasia, and Data from the Australian Bureau of main components Hb A, HbA is generally normal in thalassaemia 2 statistics show a sustained increase and HbF. At birth the proportions unless there is a co-existing iron in permanent migration to SA of of haemoglobins A, A , and F are deficiency or chronic inflammatory 2 people from areas with higher rates approximately 29-34%, 1-1.5% and disease. of haemoglobinopathy. 65-70% respectively (Figure 1a).

Haemoglobinopathies Thalassaemias and variant CBE is an important screening tool haemoglobins are inherited disorders. Some result in decreased synthesis and often, but not always, provides of globin chains, and these are a clue to diagnosis termed ‘thalassaemic’; others, the variant haemoglobins, have altered physicochemical properties the best- Table 1 Top 10 source countries SA 2012-2013 Figure 1 HbF to HbA known example being HbS, which is conversion Birth country Born Born Total associated with sickling crises in here overseas the homozygous (HbSS) form or, United Kingdom 911 1732 2643 if co-inherited, with beta (b) Fetal Hb thalassaemia or HbC. India* 922 921 1843 China* 512 917 1429 The most severe syndromes occur Fetal Philippines* 399 508 907 HbA2 1-1.5% when all a-globin genes are mutated HbA 29-34% New Zealand 41 252 693 (hydrops fetalis) or both b-globin HbF 65-70% genes (thalassaemia major). Sri Lanka* 229 273 502 In general, the inheritance of multiple Iran* 190 302 492 mutations in the same gene family Malaysia* 0 470 470 Adult Hb results in more severe syndromes (like sickle cell disease or beta South Africa 217 201 418 Adult thalassaemia intermedia or major), HbA2 + HbF 3% Afghanistan* 134 284 418 HbA 97% = 2a+2b whereas the co-inheritance of a and Other 1849 3204 5053 b mutations together often results in HbF starts converting to HbA Total 5880 9064 14944 shortly prior to birth and a less severe condition than either normally reaches adult levels mutation on its own. *regions where haemoglobinopathies are endemic at around 9 months of age

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The switch from fetal to adult Figure 2 The ‘malaria belt’ haemoglobin starts in the perinatal period and approaches adult levels Natural global origins of haemoglobinopathies at around 9 months of age (Figure 1b). For this reason detecting beta thalassaemia and beta haemoglobin variants before the age of 9 months may not be possible.

Haemoglobin variants Common b-globin variants S, E, C and D and some rare a-globin variants such as Constant Spring are detectable using HPLC.

HbS (sickle cell) is endemic in West Africa and in Afro-Caribbean populations around the world (Figure 2). S is also seen in people of Arabic ethnicity. HbE trait is common in South-East Asia but is in a thalassaemia which in most cases – familial origin/partner familial clinically insignificant and even in the requires genetic testing for diagnosis origin from a region where homozygous state (HbEE) it tends to and is mostly reserved for prenatal/ haemoglobinopathy is endemic. be mild. It is of more concern when antenatal testing. Partner testing is highly recommended co-inherited with b thalassaemia. if screen positive or suggestive of HbC is another variant that can cause 4 gene deletion (hydrops fetalis) haemoglobinopathy. significant disease when co-inherited is associated with spontaneous with HbS or beta thalassaemia. Whilst miscarriages and fetal death. If a fetus n All other patients with unexplained less common than S or E, it is more does survive to delivery it invariably persisting low MCH (with or frequent in populations from western dies shortly after birth. without microcytosis) i.e. iron Africa, Oman and Thailand. replete, normal thyroid functions 3 gene deletion (HbH disease) and no evidence of chronic disease. Thalassaemia produces a syndrome of varying Thalassaemia is more difficult severity, depending on the specific What to request to diagnose than the variant mutations. Severe cases may be CBE, iron studies (if the status is haemoglobins. transfusion-dependent, but most unknown – this information is very have milder degrees of anaemia. important to the laboratory when Beta thalassaemia interpreting results) and haemoglobin Most carriers of b thalassaemia trait 2 gene deletion (thalassaemia trait) variant analysis. will have increased HbA2, but there is benign, with microcytosis, but are rare situations where the HbA2 has no clinical consequences for the Clinical notes are always important is normal, these include severe iron carrier. Its importance lies in the when requesting any pathology deficiency and hypothyroidism. Beta risk of a more severe syndrome in test and particularly so for thalassaemia is common around the children of a carrier. haemoglobinopathy, please include Mediterranean (southern Europe partner history. ¥ and North Africa), on the Indian 1 gene deletion can be associated subcontinent and amongst populations with normal red cell indices. from Africa and South East Asia. Did you know? > A patient with recently resolved When to screen? iron deficiency may have a microcytic, hypochromic blood Did you know? Screening is recommended in the Hyperthyroidism, particularly in picture for up to four months after > following situations. starting iron therapy. Red cell those with Grave’s disease, can indices gradually return to normal n Women planning pregnancy or mimic beta thalassaemia trait. as circulating microcytic cells are currently pregnant with: replaced by normocytic red cells. – low MCH (with or without Unless there is some urgency Alpha thalassaemia (e.g. in pregnancy) it is better to microcytosis) The severity of a thalassaemia delay haemoglobinopathy testing depends on the number of genes – family history/partner history for several months after correction of iron deficiency. deleted. HPLC is usually normal of haemoglobinopathy

SA Pathology Newsletter > 3 – 2015 PAGE 7 www.sapathology.sa.gov.au

Vitamin B12 Deficiency:B12Active Dr Mohamed Saleem B12 Assay

Vitamin B12, also called cobalamin, plays a fundamental role in the formation of blood and the normal functioning of the brain and nervous system. The true prevalence of B12 deficiency in the Australian population is unknown, although studies suggest that it may be as high as 23%. The incidence appears to increase with age (>65 years) and also with the ubiquitous use of gastric acid-blocking agents. Symptoms of deficiency may be ill defined and a high index of suspicion is required for testing.

Symptoms Causes Deficiency may also occur at times of increased requirement such as in B12 deficiency can interrupt key Absorption of B12 requires: pregnancy and during lactation. biochemical pathways disturbing DNA n adequate gastric acid synthesis resulting in megaloblastic n intrinsic factor Who to test? anaemia and adverse effects on the nervous system and other organs. n and a functional terminal ileum. Patients with symptoms or signs of Deficiency is most commonly seen in: B12 deficiency including anaemia A full blood count which shows n pernicious anaemia where (macrocytic anaemia or macrocytosis) anaemia and macrocytosis has autoimmune destruction of gastric and patients with suspected traditionally prompted investigations parietal cells causes a concurrent neuropsychiatric abnormalities should for B12 deficiency. The presence of loss of intrinsic factor be tested for B12 deficiency. oval macrocytes and hypersegmented n total or subtotal gastrectomy and neutrophils (figure 2) has been Other groups where testing may gastric bypass procedures considered to be of high diagnostic be considered include the elderly, accuracy although there are other n exocrine pancreatic failure long-term vegans, patients who abuse non-specific causes for this finding n loss or disease of the terminal ileum alcohol, people on drugs that interfere (e.g. iron deficiency anaemia). (impedes absorption of B12) with B12 absorption (such as long- If untreated, deficiency may lead to n intestinal bacterial overgrowth term H2 receptor antagonists, proton severe anaemia and a broad range (may consume B12). pump inhibitors or metformin) and of neurological symptoms including patients with inflammatory bowel peripheral neuropathy, irritability, disease, gastric or small intestine tiredness and mild deterioration of resection. memory and cognitive ability.

Importantly, B12 deficiency may Up to 30% of patients with B12 present without any haematological abnormalities at all. Severe deficiency may show total serum deficiency causes subacute combined degeneration of the spinal cord. B12 levels in the lower normal range In pregnancy, maternal B12 deficiency is associated with neural tube defects B12 deficiency due to poor nutrition Laboratory testing in infants and deficiency in childhood is rare, particularly given the small Serum B12 is bound to two major is associated with developmental daily requirement (1-5 mg/day) and carrier proteins; delay and failure to thrive. its abundant presence in animal products.B12 Populations at risk for 1 Transcobalamin I, also called Impaired DNA synthesis may also nutritional deficiency include the Haptocorrin (HC) binds to the affect other rapidly dividing cells elderly with a poor intake of meat major portion of plasma B12. causing glossitis, gastrointestinal and dairy products, chronic alcoholics This complex is not active in symptoms and infertility. and strict vegans. delivering B12 to cells.

SA Pathology Newsletter > 3 – 2015 PAGE 8

2 Transcobalamin II binds to Figure 1 B12 binding B12 forming a complex called holotranscobalamin (holoTC, ACTIVE B12 INACTIVE B12 commonly referred to as active B12 delivered toB12 cells No B12 delivered to cells B12). This complex is active in delivering B12 to cells. (Figure 1) B12 B12 B12 Serum B12 holoTC CELLS HC Total Serum B12 is the most common test of B12 status and measures TII TI the sum of inactive (HC) and active B12 (HoloTc). In clinical situations TII binds 20-30% of circulating B12 where there is a significant change in the inactive fraction total serum B12 may not reflect tissue status. Inactive B12 is decreased in Active B12 levels give a better pregnancy and oestrogen therapy but may be increased in renal failure indication of B12 status and haematological malignancies. Therefore tissue deficiency (of active B12) may occur despite apparently True deficiency is very unlikely Poor conversion of homocysteine to normal serum total B12 levels and above this level. methionine in B12 deficiency may vice versa. Up to 30% of patients cause an elevated fasting plasma with B12 deficiency may show total Intrinsic Factor and Parietal Cell homocysteine level. serum B12 levels in the lower normal Antibodies range. Intrinsic Factor Antibodies (IFA) Methylmalonic acid (MMA) and Parietal cell antibodies may be Like homocysteine, MMA also has Active B12 helpful in supporting a diagnosis poor specificity as elevations may Active B12 levels give a better of pernicious anaemia. Whilst the occur in rare inherited disorders indication of the B12 available for presence of IFA is virtually diagnostic and in chronic kidney disease. tissue use. Levels ≤30pmol/L are of pernicious anaemia, they are Poor conversion of methylmalonyl considered to be deficient; in a detected in only about 50% of cases Coenzyme A to succinyl Coenzyme minority of patients levels above this and B12 treatment can cause false A in B12 deficiency may cause an may still be associated with tissue IFA negatives. elevated serum level of MMA. deficiency. Patients in whom there In the absence of these conditions a is clinical suspicion of deficiency Homocysteine significantly elevated MMA strongly may benefit from homocysteine or A normal plasma homocysteine supports B12 deficiency. methylmalonic acid analysis. makes B12 deficiency unlikely; however it has limited specificity Summary To assist diagnosis within the because elevations occur in n B12 deficiency is common. low-normal total serum B12 group, inherited and acquired disorders, n Symptoms may be ill-defined and a SA Pathology will automatically including folate and pyridoxine high index of suspicion is necessary perform an active B12 on all samples (B6) deficiency and particularly in to test. with total B12 levels <260 pmol/L. patients with chronic kidney disease. n B12 exists as active and inactive forms in the blood. Figure 2 Blood film – megaloblastic anaemia n Total serum B12 assay measures active and inactive forms and is thus prone to false positives and Hyper-segmented negatives. neutrophil n An active B12 assay measures only the active form and is superior for detecting deficiency. n SA Pathology uses active B12 to Oval macrocytes confirm deficiency when the total serum B12 result is in the borderline low range. ¥

SA Pathology Newsletter > 3 – 2015 PAGE 9 www.sapathology.sa.gov.au Multi-drug resistant aspergillosis infection Globally, the number of life-threatening fungal infections and the death toll associated with them is just as high as for tuberculosis or malaria. Aspergillus fumigatus is the most common species of fungus to cause disease in individuals with an immunodeficiency. Multi-triazole resistant aspergillosis has been emerging in Europe, Africa, and Asia over the past decade but until this study had not been reported in Australia.

The importance of SA Pathology’s European researchers believe that National Mycology Reference the high rate of drug-resistant strains Centre research was highlighted for has evolved in the environment in international delegates at a recent response to the extensive use of conference on fungal infections in fungicidal sprays used in agriculture. Melbourne. Dr Sarah Kidd published For example, the bulbs of tulips grown the work of her team in the journal commercially in Holland for export are Mycoses, describing how strains of dipped in fungicides to preserve them. the common opportunistic fungus Aspergillus fumigatus that are Other point mutations have also been resistant to first-line treatments such characterised in clinical A. fumigatus as triazole antifungal drugs, have isolates, however their relationship been identified for the first time in to agricultural fungicides is yet to be Aspergillus fumigatus Australia. clarified. a closely-related, morphologically The resistance has been attributed The Australian picture similar, ‘sibling species’ with inherent to a range of point mutations in the resistance to the triazoles, was In 2009, a 12-month prospective cyp51A gene of the fungus, leading to identified. international surveillance study, amino acid substitutions in the protein which included one Melbourne targeted by the triazoles. Mutations More recently a retrospective tertiary hospital, found no evidence have been identified in environmental examination by the National Mycology for triazole resistant A. fumigatus in isolates as well as those from azole- Reference Centre of A. fumigatus that hospital. However, one isolate naïve patients. species antifungal susceptibility of Neosartorya pseudofischeri, data, collected between 2000 and 2013 identified thirteen isolates with an elevated minimum inhibitory concentration to one or more of voriconazole, posaconazole, or itraconazole. Further analysis of these isolates revealed two that carried the same fungicide-associated cyp51A resistance mutations seen in Europe.

These two isolates were from invasive aspergillosis patients from Sydney in 2004 and Melbourne in 2012. The 2004 case had no known travel history and almost 8 years of exposure to itraconazole prior to A. fumigatus isolation, while the 2012 case had Photomicrograph of Aspergillus infection in human tissue recently travelled to Europe.

SA Pathology Newsletter > 3 – 2015 PAGE 10 Four isolates had other mutations conferring triazole resistance. Three Request antifungal susceptibility isolates had no resistance-associated cyp51A mutations and resistance testing for all clinically significant was presumably mediated by as yet Aspergillus isolates aspergillosis undiscovered mechanisms. Another four isolates were definitively Who’s at risk? Recommendations identified asA. lentulus, another closely related triazole-resistant People most at risk of infection Based on increasing identification member of the A. fumigatus complex. include those with weakened or of triazole resistant A. fumigatus compromised immune systems, globally, and coupled with this new Nation-wide prospective surveillance transplants patients or those evidence for both local and a probably for triazole-resistant A. fumigatus, suffering from various types of imported fungicide-associated including environmental surveillance, cancer. Aspergillus fumigatus is aspergillosis case, we recommend is lacking, but will be important the most prevalent cause of invasive Australian clinicians be alert to the to accurately assess the scale of mould infections in the haematology possibility of infection with triazole- the triazole resistance problem in and solid organ transplant setting. resistant Aspergillus species Australia. Australian treatment guidelines including inherently resistant sibling recommend the use of triazole species such as A. lentulus and Australia does use triazole-based antifungals, particularly voriconazole, N. pseudofischeri. pesticides in agriculture and is not for first-line treatment of invasive immune to the antifungal resistance aspergillosis. Definitive species identification and problems encountered in other parts antifungal susceptibility testing is of the world. Given that triazole Dr Kidd’s recent research has recommended for all Aspergillus resistant isolates are associated with discovered some aspergillosis isolates from patients at risk for mortality rates up to 88% higher than infections are caused by strains invasive fungal diseases, especially in susceptible isolates, Australian resistant to the whole class of drugs cases where the patient has recently clinical practice needs to take this usually used to treat them. travelled overseas or has been taking into account. antifungal drugs for long periods. ¥

RURAL ROUNDUP 50 years in Whyalla Much has changed over fifty years and Field Days SA Pathology took the opportunity to With its state-wide network of reflect on the achievements of staff past The Yorke Peninsula Field Days at laboratories SA Pathology has a long and present at a recent local celebratory Paskeville are always a big event on the history of supporting and working in dinner. What has remained constant is country calendar, in fact it is the largest regional South Australian communities. the commitment of SA Pathology and regular agricultural event in the nation, In August we celebrated 50 years of its staff to both the population and the and SA Pathology was there. service to the people of the west coast medical community of the west coast. from our Whyalla laboratory. Today two out of every three tests are During the 1950’s and 60’s, regional performed in Whyalla itself ensuring centres in SA saw hospital services results are readily and rapidly boosted to cater for the influx of new available, with the remaining third workers, and in response IMVS (now conducted in our main laboratories SA Pathology) established a laboratory in Adelaide. Speaking at the dinner, in Whyalla in 1965. past Director of both IMVS and Whyalla Hospital Professor Brendon Kearney Originally operating from a room in the said it was this level of crucial clinical nurses’ home, it was run by a handful of support that made possible services staff, analysing a few thousand samples like the hospital’s cancer hub. annually. Within five years the lab was Maitland processing over 40,000 tests a year. Whyalla joins our Wallaroo and Maitland has a new patient centre. Mt Gambier laboratories with 50 years See page 3 for location and opening of regional service. hours.

SA Pathology Newsletter50 > 3 – 2015 PAGE 11 www.sapathology.sa.gov.au i i i i i H3N2Influenza andi i other RespiratoryH1N1 H3N 9Pathogensi update H1N1The winter of 2015 saw yet another big influenza season here in South Australia with the unprecedented dominance of the Influenza B virus.

The latest Australian Influenza Figure 1 Australia Influenza typing data Surveillance Report states that, (WHO Influenza Centre) update whilst remaining within the range of 100 previous seasons, influenza-like illness B/Yamagata activity is increasing. 90 B/Victoria Influenza notification rates have been A(H3N2) 80 highest among those aged between A(H1N1)pdm09 5 and 9 and over 85 years with a 70 secondary peak in those aged 40 to 44 years. 60 Several other respiratory pathogens 50

have also been active including 40 Respiratory Syncytial Virus Number of samples (RSV), Parainfluenza, Rhinovirus, 30 Metapneumovirus, Adenovirus and 20 Bordetella pertussis. Table 1 lists all respiratory viral activity reported by 10 SA Pathology (including Mycoplasma 0 pneumoniae and Bordertella ACT NSW NT QLD SA TAS VIC NZ pertussis) both in the recent week Australia and year to date.

Table 1 Respiratory viral and bacterial pathogens VACCINATIONS Respiratory Week Year to pathogen ending date 2015 The seasonal influenza vaccines for 2015 appear to 04/10/15 be a good match for the circulating strains. However Influenza A 218 4127 approximately one-quarter of influenza B viruses tested are due to a lineage not contained in the trivalent Influenza B 156 5033 seasonal vaccine (TIV). RSV 37 4156 The WHO recommended the following vaccine compositions Parainfluenza 1 1 38 for the southern hemisphere winter of 2015. Parainfluenza 2 2 319 Trivalent vaccines: Parainfluenza 3 83 1533 an A/California/7/2009 (H1N1)-like virus Adenovirus 61 1429 an A/Switzerland/9715293/2013 (H3N2)-like virus Metapneumovirus 140 1886 a B/Phuket/3073/2013-like virus (Yamagata lineage) Rhinovirus 261 9263 M pneumoniae 47 642 In addition to the above Quadrivalent vaccines contained a B/Brisbane/60/2008-like virus (Victoria lineage). B pertussis 10 292

SA Pathology enquiries > Metropolitan 8222 3000 > Regional and Country 1800 188 077

SA Pathology Newsletter > 3 – 2015 PAGE 12 www.sapathology.sa.gov.au