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Introduction: Funding decisions for many health technologies occur without undergoing health technology assessment (HTA), in particular, without assessment of cost effectiveness (CE). Immunoglobulins in Australia are an interesting case study because they have been used for a long time for various rare disorders and their price is publicly available. Undertaking an HTA enables us to assess CE for an intervention for which there is limited clinical and economic evidence. This study presents a post-market review to assess the CE of immunoglobulins for the treatment of multifocal motor neuropathy (MMN) compared with best supportive care., Methods: A Markov model was used to estimate costs and quality-adjusted life-years (QALYs). Input sources included randomised controlled trials, single-arm studies, the Australian clinical criteria for MMN, clinical guidelines, previous Medical Services Advisory Committee (MSAC) reports and inputs from clinical experts. Sensitivity analyses were conducted to assess the uncertainty and robustness of the CE results., Results: The cost per patient of treating MMN with immunoglobulin was AU$275,853 versus AU$26,191when no treatment was provided, with accrued QALYs of 6.83 versus 6.04, respectively. The latter translated into a high incremental cost-effectiveness ratio (ICER) of AU$317,552/QALY. The ICER was most sensitive to the utility weights and the price of immunoglobulins. MSAC advised to continue funding of immunoglobulins on the grounds of efficacy, despite the high and uncertain ICER., Conclusions: Beyond the ICER framework, other factors were acknowledged, including the high clinical need in a patient population for which there are no other active treatments available. This case study highlights the challenges of conducting HTA for already funded interventions, and the efficiency trade-offs required to fund effective high-cost therapies in rare conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Shellfish allergy affects ~2.5% of the global population and is a type I immune response resulting from exposure to crustacean and/or molluscan proteins. The Australian Redclaw crayfish (Cherax quadricarinatus) is a freshwater species endemic to and farmed in northern Australia and is becoming an aquaculture species of interest globally. Despite being consumed as food, allergenic proteins from redclaw have not been identified or characterised. In addition, as different body parts are often consumed, it is conceivable that redclaw tissues vary in allergenicity depending on tissue type and function. To better understand food-derived allergenicity, this study characterised allergenic proteins in various redclaw body tissues (the tail, claw, and cephalothorax) and how the stability of allergenic proteins was affected through cooking (raw vs. cooked tissues). The potential of redclaw allergens to cross-react and cause IgE-binding in patients allergic to other shellfish (i.e., shrimp) was also investigated. Raw and cooked extracts were prepared from each body part. SDS-PAGE followed by immunoblotting was performed to determine allergen-specific antibody reactivity to sarcoplasmic calcium-binding protein and hemocyanin, as well as to identify redclaw proteins binding to IgE antibodies from individual and pooled sera of shrimp-allergic patients. Liquid chromatography-mass spectrometry (LC/MS) was utilised to identify proteins and to determine the proportion within extracts. Known crustacean allergens were found in all tissues, with a variation in tissue distribution (e.g., higher levels of hemocyanin in the claw and cephalothorax than in the tail). The proportion of some allergens as a percentage of remaining heat-stable proteins increased in cooked tissues. Previously described heat-stable allergens (i.e., hemocyanin and sarcoplasmic calcium-binding protein) were found to be partially heat-labile. Immunoblotting indicated that shrimp-allergic patients cross-react to redclaw allergens. IgE-binding bands, analysed by LC/MS, identified up to 11 known shellfish allergens. The findings of this study provide fundamental knowledge into the diagnostic and therapeutic field of shellfish allergy. [ABSTRACT FROM AUTHOR]

Purpose: Hepatitis C (HCV) infections are prevalent in custodial settings worldwide, yet provision of antiviral therapies is uncommon. Approximately 30,000 prisoners are held in Australian prisons at any one time, with more than 30 per cent testing positive for HCV antibodies. Prisoners have been identified in the National Hepatitis C Strategy as a priority population for assessment and treatment. The purpose of this paper is to examine the rates of HCV testing and treatment, as well as barriers and opportunities for development of infrastructure for enhanced services.Design/methodology/approach: Interviews were conducted with 55 stakeholders from the correctional sector in each state and territory in Australia in two stages: service directors to gather quantitative data regarding rates of testing and treatment; and other stakeholders for qualitative information regarding barriers and opportunities.Findings: Of more than 50,000 individuals put in in custody in Australian prisons in 2013, approximately 8,000 individuals were HCV antibody positive, yet only 313 prisoners received antiviral treatment. The barriers identified to assessment and treatment at the prisoner-level included: fear of side effects and the stigma of being identified to custodial authorities as HCV infected and a likely injecting drug user. Prisoners who came forward may be considered unsuitable for treatment because of prevalent mental health problems and ongoing injecting drug use. Provision of specialist hepatitis nurses and consultants were the most frequently recommended approaches to how prison hepatitis services could be improved.Originality/value: Many personal and systems-level barriers relevant to the delivery of HCV treatment services in the custodial setting were identified. Ready access to skilled nursing and medical staff as well as direct acting antiviral therapies will allow the prison-sector to make a major contribution to control of the growing burden of HCV disease. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals. [ABSTRACT FROM AUTHOR]

Objective: Simultaneous antibody testing during screening for autoimmune conditions is discouraged. The incidence of positive extractable nuclear antigen (ENA) in the setting of a negative antinuclear antibody (ANA) has been reported as low. Our objective was to characterize the frequency of diagnosis of new ANA‐associated rheumatic disease (AARD) in the setting of a negative ANA with a positive ENA. Methods: This was a 7‐year retrospective study from a multicenter tertiary health network in Australia. Clinical information was sought on patients over 18 years old who had a negative ANA but positive ENA test result. Results were extracted from hospital computer systems. Results: From March 19, 2011, to July 23, 2018, ENA testing was ordered simultaneously with an ANA test on 4,248 occasions in 3,484 patients. ANA was positive in 2,520 patients (59.3%) and ENA was positive in 1,980 patients (46.6%). Among positive ANA patients, ENA was positive in 1,563 patients (62.0%). Among 1,728 negative ANA tests, ENA was positive in 417 (24.1%) (P < 0.001). A total of 328 patients with discordant ANA/ENA results had data available for further analysis, of whom 279 had no pre‐established rheumatologic condition. A new AARD was diagnosed in 17 of 279 patients, yielding a positive predictive value of 6.09% (95% confidence interval 3.59–9.58). Conclusion: Despite the higher‐than‐expected incidence of positive ENA in the setting of a negative ANA, the yield of newly diagnosed rheumatic diseases was low. Our findings support the stepwise addition of ENA requests when an ANA test result is positive and clinical suspicion of an AARD is high. [ABSTRACT FROM AUTHOR]

Little is published on cytomegalovirus (CMV) serological screening at the first antenatal visit or the contemporary CMV seroprevalence rates among the Australian pregnant population. We performed a retrospective analysis of public hospital births in a major tertiary centre (n = 840) over a two month period. We found that 13.6% (95% confidence interval (CI) 11.4–16.1%) of women had been screened for CMV at their first antenatal visit with their general practitioner. Of these, 43.0% (95% CI 34.3–52.1%) were CMV seronegative and therefore susceptible to primary infection. Seronegative women were also more likely to have been born in an economically developed country, to live in a socio‐economically advantaged postcode and to be nulliparous. The information from this study may help guide future studies of congenital CMV risk reduction strategies. [ABSTRACT FROM AUTHOR]

Background To determine if dried blood spot specimens (DBS) can reliably detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, we compared the SARS-CoV-2 IgG antibody response in paired serum and eluates from DBS specimens. Methods A total of 95 paired DBS and serum samples were collected from 74 participants (aged 1–63 years) as part of a household cohort study in Melbourne, Australia. SARS-CoV-2 IgG antibodies specific for the receptor-binding domain (RBD) and S1 proteins between serum and eluates from DBS specimens were compared using an FDA-approved ELISA method. Results Among the 74 participants, 42% (31/74) were children and the rest were adults. A total of 16 children and 13 adults were SARS-CoV-2 positive by polymerase chain reaction. The IgG seropositivity rate was similar between serum and DBS specimens (18.9% (18/95) versus 16.8% (16/95)), respectively. Similar RBD and S1-specific IgG levels were detected between serum and DBS specimens. Serum IgG levels strongly correlated with DBS IgG levels (r = 0.99, P  < 0.0001) for both SARS-CoV-2 proteins. Furthermore, antibodies remained stable in DBS specimens for >3 months. Conclusions DBS specimens can be reliably used as an alternative to serum samples for SARS-CoV-2 antibody measurement. The use of DBS specimens would facilitate serosurveillance efforts particularly in hard-to-reach populations and inform public health responses including COVID-19 vaccination strategies. [ABSTRACT FROM AUTHOR]

Background: Suboptimal endometrial receptivity is a key factor behind in vitro fertilisation (IVF) implantation failure. Direct clinical tests of the endometrium of natural killer (NK) cells and endometrial receptivity analysis (ERA) are controversial. Aims: To examine the current practice of endometrial receptivity tests (NK cells and ERA) and immunological treatments (corticosteroids, anticoagulants, antiplatelets, intravenous immunoglobulin, Intralipid, other) among fertility specialists in Australia and New Zealand. Methods: A prospective 23‐item web‐based survey was distributed by email via the Fertility Society of Australia and New Zealand, between August and October 2020. Data were collected and analysed using Qualtrics. Results: Of 238 fertility specialists, 90 completed the survey (response rate 37.8%). ERA (48/90, 53.3%) was most commonly ordered, followed by uterine NK (uNK) (36/90, 40.0%) and peripheral blood NK (pNK) (12/90, 13.3%). For all tests, the most common indication was recurrent implantation failure (RIF) (41/48, 22/36, 6/12; 85.4%, 61.1%, and 50.0%, respectively for ERA, uNK and pNK). Of those that did not offer these tests, the main reason cited was insufficient evidence (30/42, 47/54, 68/78; 71.4%, 87.0%, and 87.0%). A third of specialists offered empirical immunological treatment for RIF (30/90, 33.3%): anticoagulants (28/30, 93.3%), antiplatelets (27/30, 90.0%), and corticosteroids (25/30; 83.3%). The majority of specialists (56/90, 62.2%) stated they had refused a patient request for endometrial testing or treatment. Conclusions: Tests for presumed endometrial receptivity pathology are often used in Australia and New Zealand. Immunological treatments for RIF are commonly employed empirically, without strong evidence of their effectiveness or safety. Further studies should focus on education and clinical adherence to evidence‐based guidelines. [ABSTRACT FROM AUTHOR]

Purpose: To examine the response or pre- and postmatch salivary immunoglobulin A concentration ([s-IgA]) to Australian Football League (AFL) match play and investigate the acute and cumulative influence of player workload and postmatch [s-IgA] after repeated participation in AFL match play. Methods: Eleven elite AFL athletes (21.8 ± 2.4 y, 186.9 ± 7.9 cm, 87.4 ± 7.5 kg) were monitored throughout 3 matches during the preseason that were separated by 7 d. Saliva samples were collected across each AFL match at 24 h and 1 h prematch and 1, 12, 36, and 60 h postmatch to determine [s-IgA]. Global positioning systems (GPS) with integrated triaxial accelerometers were used to determine total player workload during match play. Hypothesis testing was conducted for time-dependent changes in [s-IgA] and player load using a repeated-measures ANOVA. Results: Player load during match 3 (1266 ± 124.6 AU) was significantly (P < .01) greater than in match 1 (1096 ± 115.1 AU) and match 2 (1082 ± 90.4 AU). Across match 3, [s-IgA] was significantly (P < .01) suppressed at 2 postmatch measures (12 and 36 h) compared with prematch measures (24 and 1 h), which coincided with significantly (P < .01) elevated player load. Conclusion: The findings indicate that an increase in player load during AFL preseason match play resulted in compromised postmatch mucosal immunological function. Longitudinal assessment of AFL-match player load and mucosal immunological function across the first 60 h of recovery may augment monitoring and preparedness strategies for athletes. [ABSTRACT FROM AUTHOR]

Introduction: The advent of RhD immunoglobulin prophylaxis to prevent maternal RhD alloimmunization has reduced the incidence of this condition and its associated poor outcomes. Consequently, non-D Rh antibodies now account for a greater proportion of alloimmunized pregnancies. These antibodies have been the subject of comparatively little research. This study investigated the incidence and clinical outcome of pregnancies affected by non-D Rh alloimmunization at an Australian tertiary maternity service.Material and Methods: This was a retrospective study of all pregnancies with non-D Rh antibodies (namely anti-C, -E, -c, -e, -Cw as well as the compound antibodies anti-CD, -cE and -ce) managed at the Royal Women's Hospital, Victoria, Australia, from 2009 to 2013 inclusive. Information collected included maternal demographics, details of the antibodies, course of the pregnancy and neonatal outcomes.Results: During the study period, 115 non-D Rh alloimmunized pregnancies were identified in 102 mothers. Forty-nine pregnancies reached the critical titer (> 16) from non-D Rh alone and 11 fetuses received intrauterine red blood cell transfusion. Labor was induced or cesarean section performed in 38 cases. Forty-three neonates were admitted to the special care nursery and 59 received phototherapy. Nine received treatment for anemia and 10 neonates received intravenous immunoglobulin.Conclusions: Non-D Rh alloimmunization is a relatively uncommon complication of pregnancy, occurring in only .33% of pregnancies in the study period. It can lead to significant fetal/neonatal morbidity (and may lead to mortality). The most severe outcomes (including perinatal deaths) were mostly associated with the compound antibodies anti-CD and anti-cE, or a non-D Rh antibody in conjunction with anti-D. [ABSTRACT FROM AUTHOR]

Aim: Intravenous immunoglobulin (IVIG) is an expensive therapy used in immunodeficiency and autoimmune disorders. Increasing demands and consequent shortages result in a need for usage to conform to guidelines.Method: We retrospectively evaluated IVIG use for neuroimmunological indications and adherence to existing guidelines in a major Australian paediatric hospital between 2000 and 2014.Results: One-hundred and ninety-six children (96 male, 100 female; mean age at disease onset 6y 5mo [range 3mo-15y 10mo], mean age at first IVIG dose 7y 2mo [range 3mo-16y 5mo]) received IVIG for neuroimmunological indications during the study period (28.1% had Guillain-Barré syndrome), representing 15.5% of all hospital indications. In total, 1669 IVIG courses were administered (total 57 221g, median 78g/patient, range 12-5748g). The highest median numbers of courses were in chronic inflammatory demyelinating polyneuropathies, opsoclonus-myoclonus ataxia syndrome, suspected immune-mediated epilepsies, and Rasmussen's encephalitis. Adverse reactions occurred in 25.5% of patients, but these were mostly minor. Outcome at follow-up was best in anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, Guillain-Barré syndrome, and myasthenia gravis, and worst in Rasmussen's encephalitis and epilepsies. The total cost of IVIG was US$2 595 907 (median $3538/patient, range $544-260 766). Of patients receiving IVIG, 45.4% to 57.1% were given the therapy for 'weak' indications or indications 'not listed' in international guidelines. Some entities commonly treated with IVIG in current practice, such as anti-NMDAR encephalitis and transverse myelitis, are not listed in most guidelines.Interpretation: Our study demonstrates that IVIG is generally well tolerated but expensive, and discloses discrepancies between guidelines and clinical practice in paediatric neurology, suggesting both the need for greater adherence to current recommendations, and for recommendations to be updated to accommodate emerging indications. [ABSTRACT FROM AUTHOR]

Background: Physical training by female military trainees can put them at risk of iron deficiency and inferior health and performance. Purpose: To determine the effect of iron supplementation on iron status, fitness, fatigue, and leisure activities. Material and Methods: In this randomised, double-blind, placebo-controlled trial, female officers-in-training were randomly allocated to treatment (n = 25, 18 mg iron) or placebo tablets (n = 24). Outcomes were iron status, fitness, fatigue, and leisure activity at baseline, seven weeks and 13 weeks. Results: Ferritin declined by midpoint in the placebo group (P = 0.001). There was a treatment effect in the second half of the trial in emotional fatigue (-4.2 to -0.6 95% CI, P = 0.04). There was a negative relationship with iron intake for emotional fatigue (OR 0.61; 0.44 to 0.87 95% CI; P = 0.006) and positive for vigour (OR 1.51; 1.08 to 2.11 95%CI; P = 0.016) and small negative association between initial dietary iron intake and initial serum ferritin (0.2 to 9.2 μg/L 95% CI; P = 0.042). Conclusion: Officer training affects iron status and iron supplementation improves indicators of iron status and emotional fatigue in female officers-in-training. [ABSTRACT FROM AUTHOR]

The article presents the findings of a research conducted on 20 cases of canine neural angiostronglyosis (NA) with cerebrospinal fluid (CSF) in eastern Australia, during 2002-2005. It discusses the methodology of the research including retrospective cohort of 59 dogs was contrasted with a series of 22 new cases, where NA was diagnosed by the presence of both eosinophilic pleocytosis and anti-Angiostrongylus cantonensis immunloglobulins (IgG) in CSF, determined by ELISA or Western blot. It concludes that dogs are an important sentinel species for NA.

Fetomaternal or neonatal alloimmune thrombocytopenia (NAIT) is a rare but serious condition associated with significant fetal and neonatal morbidity and mortality. The most useful predictor of severe disease is a history of a sibling with an antenatal intracranial haemorrhage. However, NAIT can occur during the first pregnancy and may not be diagnosed until the neonatal period. Antenatal treatment options include maternal intravenous immunoglobulin (IVIG) and corticosteroid treatment, fetal blood sampling (FBS) and intrauterine platelet transfusion (IUT) and early delivery. FBS (with or without IUT) can be used to direct and monitor response to therapy, and to inform mode and timing of delivery. However, this procedure is associated with significant risks, including fetal death, and is generally now reserved for high-risk pregnancies. This review highlights the current understanding of the epidemiology and pathophysiology of NAIT and summarises current approaches to investigation and management. It also introduces the newly established Australian NAIT registry. Owing to the relative rarity of NAIT, accruing sufficient patient numbers for studies and clinical trials at an institutional level is difficult. This national registry will provide an opportunity to collect valuable information and inform future research on this condition. [ABSTRACT FROM AUTHOR]

Background: The first wave of pandemic influenza A(H1N1)2009 (pH1N1) reached New South Wales (NSW), Australia in May 2009, and led to high rates of influenza-related hospital admission of infants and young to middle-aged adults, but no increase in influenza-related or all-cause mortality. Methodology/Principal Findings: To assess the population rate of pH1N1 infection in NSW residents, pH1N1-specific haemagglutination inhibition (HI) antibody prevalence was measured in specimens collected opportunistically before (2007-2008; 474 specimens) and after (August-September 2009; 1247 specimens) the 2009 winter, and before the introduction of the pH1N1 monovalent vaccine. Age- and geographically-weighted population changes in seroprevalence were calculated. HI antibodies against four recent seasonal influenza A viruses were measured to assess cross-reactions. Pre- and post-pandemic pH1N1 seroprevalences were 12.8%, and 28.4%, respectively, with an estimated overall infection rate of 15.6%. pH1N1 antibody prevalence increased significantly - 20.6% overall - in people born since 1944 (26.9% in those born between 1975 and 1997) but not in those born in or before 1944. People born before 1925 had a significantly higher pH1N1 seroprevalence than any other age-group, and against any seasonal influenza A virus. Sydney residents had a significantly greater change in prevalence of antibodies against pH1N1 than other NSW residents (19.3% vs 9.6%). Conclusions/Significance: Based on increases in the pH1N1 antibody prevalence before and after the first pandemic wave, 16% of NSW residents were infected by pH1N1 in 2009; the highest infection rates (27%) were among adolescents and young adults. Past exposure to the antigenically similar influenza A/H1N1(1918) is the likely basis for a very high prevalence (49%) of prepandemic cross-reacting pH1N1 antibody and sparing from pH1N1 infection among people over 85 years. Unless pre-season vaccine uptake is high, there are likely to be at least moderate rates including some life-threatening cases of pH1N1 infection among young people during subsequent winters. [ABSTRACT FROM AUTHOR]

Background and Objectives In 2005, the Australian Red Cross Blood Service implemented a malaria antibody testing based strategy for donors with a history of travel/residence in a malaria endemic country or a past history of malaria. This report assesses the safety and efficacy of the strategy since inception. Materials and Methods Eligible blood donors were tested using the Newmarket malarial antibody EIA at least 4 months after their last potential exposure. Where EIA non-reactive their quarantined red cells were considered for transfusion and they were re-instated for cellular component manufacture at their next donation. The efficiency and safety of this strategy were evaluated based on the additional number of components recovered for transfusion and the observed incidence of transfusion transmitted malaria (TTM) respectively. Results Of the repeat reactive donors, 2696 (> 99·99%) were PCR negative whilst one was PCR positive with very low level parasitaemia. The average number of RBCs and platelets recovered per annum was 64 967 and 7398 representing 7·9 and 5·5% respectively of their annual production. No new TTM cases were recorded and the observed TTM rate of zero was consistent with the upper 95% CI for the pretesting TTM incidence of 0·9 per million donations. Conclusion The study findings support the efficacy and safety of a targeted screening strategy combining a sensitive antibody screening test with a 4-month cellular component restriction period for donors with a declared malarial risk. The TTM risk in Australia remains low and did not measurably change after implementing the testing strategy. [ABSTRACT FROM AUTHOR]

To determine hepatitis C incidence and the demographic and behavioural predictors in seronegative drug injecting prisoners. Prisoners in New South Wales, Australia who: were aged 18 years and over; reported IDU; had been continuously imprisoned; had a documented negative HCV antibody test result in prison in the last 12 months; provided written informed consent. Subjects were interviewed about their demographic characteristics and detailed risk factors for transmission prior to, and since, imprisonment. A blood sample was collected to screen for HCV antibodies by ELISA and RNA by PCR. Of 253 inmates recruited, 120 were continuously imprisoned and included in this analysis. Sixteen acquired HCV infection indicating an incidence of 34.2 per 100 person years (CI: 19.6–55.6). Risk factors for transmission included prior imprisonment, methadone treatment and greater than 10 years of education. Although the frequency of injecting was reduced in prison, 33.6% continued to inject drugs, most commonly methamphetamine, and 90% of these reported sharing injecting equipment. Prison inmates were at high risk of HCV infection, despite some reduction in high-risk behaviours and access to prevention services. To prevent HCV transmission in prisons, better prevention strategies are required. [ABSTRACT FROM AUTHOR]

Summary. Sera collected from Australian wild rabbits prior to the escape of rabbit haemorrhagic disease virus (RHDV) from Wardang Island were examined for RHDV antibodies using purified recombinant capsid protein VP60 expressed from baculovirus. A VP60-based indirect ELISA showed that 196 of 392 wild rabbit sera reacted (OD450>0.15) with VP60. Twenty sera (OD450 ranging from 0.15–2.47), randomly chosen from the 196 positive sera, recognized the 64 kDa VP60 in Western blot analysis, indicating that the reactivity detected in ELISA is indeed specific to the VP60 antigen. In a separate study, sera of 23 rabbits from an RHD-free area after the escape of RHDV were tested by ELISA and 21 of the 23 rabbits were found to be positive. When these rabbits were challenged with a lethal dose of RHDV, 11 out of the 23 rabbits survived. The presence of RHDV-protective antibodies in some of these rabbits suggested that they had been exposed to a pre-existing non-virulent rabbit calicivirus closely related to RHDV. These results highlight the need to study the prevalence of, and to characterize, this viral agent in order to effectively control rabbit populations in Australia and New Zealand. [ABSTRACT FROM AUTHOR]