Prevalence of gestational diabetes mellitus, maternal obesity and associated perinatal outcomes over 10 years in an Australian tertiary maternity provider.

BACKGROUND: The International Association of Diabetes in Pregnancy Study Groups (IADPSG) gestational diabetes mellitus (GDM) criteria have been heavily scrutinised with concerns that the consequent GDM prevalence increase has not been associated with improved perinatal outcomes. AIMS: At a tertiary hospital in Melbourne, Australia we aimed to evaluate prevalence trends for GDM, type 2 diabetes (T2DM), maternal obesity and large-for-gestational age (LGA) and assess changes in perinatal outcomes following IADPSG criteria uptake in 2015. METHODS: A retrospective cohort study of singleton births from 20 weeks' gestation was conducted between 1st January 2011 and 31st December 2020. Maternal characteristics and perinatal outcomes were extracted from medical records. RESULTS: 52,795 pregnancies were included. GDM prevalence increased 2.7 times from 8.9% in 2011 to 23.7% in 2020 and increased annually by 8.59% (95%CI 7.77, 9.42). The rate of T2DM increased annually by 11.69% (95%CI 7.72, 16.67). Obesity prevalence increased annually by 3.18% (95%CI 2.58, 3.78). Induction of labour (IOL) prevalence increased annually by 8.35% (95%CI 5.69, 11.06). LGA prevalence remained unchanged. Increasing maternal obesity was the major contributing factor for LGA prevalence. CONCLUSIONS: From 2011 to 2020 GDM, obesity and T2DM prevalence increased significantly, with associated increased IOL, without change in LGA rates. Prospective studies are required to explore interactions between GDM, obesity, LGA and obstetric interventions.

Sodium glucose co-transporter-2 inhibitor-induced diabetic ketoacidosis following tooth extraction: improving awareness among dental practitioners.

Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are a relatively new class of oral glucose lowering agents that improve glycaemic control and also provide significant cardiac and renal benefits. However, SGLT-2i use is associated with a small but significant increased risk of diabetic ketoacidosis (DKA) especially during periods of reduced oral intake such as following dental procedures, bowel preparation for colonoscopy, surgery and concurrent illness. In contrast with typical DKA, in many cases of SGLT2i-associated DKA, the blood glucose is normal or only slightly elevated, giving rise to the term euglycaemic DKA (euDKA). Patients with euDKA often present with non-specific symptoms. Moreover, their normal or only mildly elevated blood glucose levels might lead to delayed diagnosis and treatment and hence potentially life-threatening complications. Not only should patients taking an SGLT-2i be informed about the risk of euDKA, and be provided with SGLT-2i sick day management education, but clinicians should also be alert to this diagnosis.

Determinants of Cardiovascular Risk in 7000 Youth With Type 1 Diabetes in the Australasian Diabetes Data Network.

CONTEXT: Cardiovascular disease occurs prematurely in type 1 diabetes. The additional risk of overweight is not well characterized. OBJECTIVE: The primary aim was to measure the impact of body mass index (BMI) in youth with type 1 diabetes on cardiovascular risk factors. The secondary aim was to identify other determinants of cardiovascular risk. DESIGN: Observational longitudinal study of 7061 youth with type 1 diabetes followed for median 7.3 (interquartile range [IQR] 4-11) years over 41 (IQR 29-56) visits until March 2019. SETTING: 15 tertiary care diabetes centers in the Australasian Diabetes Data Network.Participants were aged 2 to 25 years at baseline, with at least 2 measurements of BMI and blood pressure. MAIN OUTCOME MEASURE: Standardized systolic and diastolic blood pressure scores and non-high-density lipoprotein (HDL) cholesterol were co-primary outcomes. Urinary albumin/creatinine ratio was the secondary outcome. RESULTS: BMI z-score related independently to standardized blood pressure z- scores and non-HDL cholesterol. An increase in 1 BMI z-score related to an average increase in systolic/diastolic blood pressure of 3.8/1.4 mmHg and an increase in non-HDL cholesterol (coefficient + 0.16 mmol/L, 95% confidence interval [CI], 0.13-0.18; P < 0.001) and in low-density lipoprotein (LDL) cholesterol. Females had higher blood pressure z-scores, higher non-HDL and LDL cholesterol, and higher urinary albumin/creatinine than males. Indigenous youth had markedly higher urinary albumin/creatinine (coefficient + 2.15 mg/mmol, 95% CI, 1.27-3.03; P < 0.001) and higher non-HDL cholesterol than non-Indigenous youth. Continuous subcutaneous insulin infusion was associated independently with lower non-HDL cholesterol and lower urinary albumin/creatinine. CONCLUSIONS: BMI had a modest independent effect on cardiovascular risk. Females and Indigenous Australians in particular had a more adverse risk profile.

Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report.

BACKGROUND: Juvenile hemochromatosis is the most severe form of iron overloading phenotype. Although rare, it should be suspected in patients who present with hypogonadotropic hypogonadism, diabetes mellitus, or cardiomyopathy without a clear cause. CASE PRESENTATION: A young Serbian male presenting with end-stage heart failure was referred for extracorporeal membrane oxygenation. An endomyocardial biopsy revealed cytoplasmic iron deposits in myocytes. His condition was stabilized with biventricular assist devices and he was listed for heart transplantation. Iron chelation therapy was commenced and resulted in rapid removal of iron burden. Serial outpatient echocardiograms demonstrated myocardial recovery such that a successful biventricular assist device explant occurred 131 days after initial implant. Targeted gene sequencing revealed a loss-of-function mutation within the HJV gene, which is consistent with juvenile hemochromatosis. CONCLUSIONS: This rare case of a patient with juvenile hemochromatosis associated with a HJV mutation provides histologic evidence documenting the reversal of associated end-stage heart failure, requiring emergent mechanical circulatory support, with iron chelation therapy.

The high burden of inpatient diabetes mellitus: the Melbourne Public Hospitals Diabetes Inpatient Audit.

OBJECTIVE: To determine the prevalence of diabetes in inpatients in Melbourne hospitals. DESIGN: Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. SETTING: 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. PARTICIPANTS: 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. MAIN OUTCOME MEASURES: Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. RESULTS: Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in different hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipid-lowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. CONCLUSION: The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.

The field effectiveness of routine and emergency vaccination with an inactivated vaccine against foot and mouth disease.

High potency, inactivated foot and mouth disease (FMD) vaccines may be used in non endemic countries for emergency vaccination during outbreaks in order to prevent virus spread. In endemic countries either standard or high potency vaccines are used for routine vaccination. Despite their wide use there is a shortage of data on the field effectiveness of inactivated FMD vaccines. Epidemics of FMD caused by viruses of serotype O occur frequently in Israel, where a high potency (≥6PD(50)) vaccine is used for both routine and emergency vaccination. We investigated an outbreak of FMD caused by a virus of serotype O, which took place during 2011 in a feedlot and an adjacent dairy herd. Post outbreak testing of antibodies against non-structural protein demonstrated that infection occurred in 96% of the calves that received two doses of vaccine at least three months prior to the outbreak and more than 50% showed clinical signs consistent with FMD. Replacement heifers that had been vaccinated 3-5 times with the last vaccination administered 7 months prior to the outbreak were all infected and 18% showed clinical signs. Testing of cattle sera of the same vaccination status as the affected cattle demonstrated low neutralizing antibody (NA) titers against the field virus strain and an r(1) value of 0.37 compared to the vaccine strain. In contrast, cattle vaccinated only once but up to two weeks before the outbreak, were almost all protected from clinical disease and to a lesser extent, protected from FMD virus infection, despite low NA titers. We conclude that emergency vaccination was highly effective due to a mechanism not associated with NA, whereas routine vaccination with the same vaccine formulation provided only limited protection due to poor longevity of the elicited immunity and low matching with the field strain (despite an r(1) higher than 0.3).

Foot-and-mouth disease virus epitope dominance in the antibody response of vaccinated animals.

Five neutralizing antigenic sites have been identified on the surface of serotype O foot-and-mouth disease virus (FMDV). A set of mAb neutralization-escape mutant viruses was used for the first time to evaluate the relative use of known binding sites by polyclonal antibodies from three target species: cattle, sheep and pigs. Antibodies to all five neutralizing antigenic sites were detected in all three species, with most antibodies directed against antigenic site 2, followed by antigenic site 1. In 76 % of cattle, 65 % of sheep and 58 % of pigs, most antibodies were directed against site 2. Antibodies specific to antigenic sites 3, 4 and 5 were found to be minor constituents in the sera of each of the target species. This implies that antigenic site 2 is a dominant neutralization immunogenic site in serotype O FMDV and may therefore be a good candidate for designing novel vaccines.

Investigations into the cause of foot-and-mouth disease virus seropositive small ruminants in Cyprus during 2007.

In 2007, serological evidence for foot-and-mouth disease (FMD) infection was found as a result of differential diagnostic testing of Cypriot sheep suspected to be infected with bluetongue or contagious ecthyma. Seropositive sheep and goats were subsequently uncovered on ten geographically clustered flocks, while cattle and pigs in neighbouring herds were all seronegative. These antibodies were specific for serotype-O FMD virus, reacting with both structural and non-structural (NS) FMD viral proteins. However, no FMD virus could be recovered from the seropositive flocks. FMD had not been recorded in Cyprus since 1964 and there has been no vaccination programme since 1984. Since all the seropositive animals were at least 3 years old and home-bred, it was concluded that infection had occurred approximately 3 years previously had passed un-noticed and died out spontaneously. It therefore appears that antibodies to FMD virus NS proteins can still be detected around 3 years after infection of small ruminants, but that virus carriers cannot be detected at this time. This unusual situation of finding evidence of historical infection in a FMD-free country caused considerable disruption and alarm and posed questions about the definition of what constitutes a FMD outbreak.

Recombinant human thyroid-stimulating hormone (Thyrogen) in thyroid cancer follow up: experience at a single institution.

BACKGROUND: Recombinant human thyroid-stimulating hormone (Thyrogen; Genzyme Corporation, Cambridge, MA, USA) (rhTSH)-stimulated serum thyroglobulin (Tg) (stim-Tg) and (131)I whole-body scanning (WBS) have been reported to allow follow up of patients with thyroid cancer without the symptoms of thyroxine withdrawal and with equivalent diagnostic information to that obtained after thyroxine withdrawal. The aim of the study was to report results of rhTSH use at the Alfred Hospital, Melbourne, from 1999 to 2006 and in particular to examine the significance of detectable serum Tg after rhTSH in relation to thyroid cancer staging and to compare the sensitivity of rhTSH-stimulated serum Tg to whole-body (131)I scanning (WBS) in the detection of residual and recurrent thyroid cancer. METHODS: The study was a retrospective chart review. RESULTS: In 90 patients, rhTSH was used for 96 diagnostic episodes and 18 doses of rhTSH were used to facilitate treatment with (131)I. In stages I and II cancer (n = 42), of three patients with stim-Tg 1-2 microg/L, none had identifiable disease, and the three patients who had stim-Tg >2 microg/L did not experience recurrent disease during follow up. In contrast, in stages III and IV cancer (n = 43) 2 of 5 with stim-Tg 1-2 microg/L had identifiable disease and 7 of 10 with stim-Tg >2 microg/L had identifiable disease. In Tg-positive, WBS-negative disease, further imaging identified persistent/recurrent disease. CONCLUSION: rhTSH was effective and safe in the management of thyroid cancer follow up for diagnosis of persistent/recurrent cancer and to enable (131)I treatment. In no case did rhTSH-stimulated WBS identify the presence of disease not also identified by raised basal Tg or stim-Tg. Therefore, in low risk cancer WBS may be omitted.

Patients presenting with severe hypotonic hyponatremia: etiological factors, assessment, and outcomes.

BACKGROUND: Although hospital-acquired hyponatremia is well described, severe community-acquired hyponatremia has been studied less extensively. AIM: To assess characteristics and outcomes of patients admitted with severe hypotonic hyponatremia (SHH) (defined as serum sodium ≤ 120 mmol/L). METHODS: All patients with serum sodium of ≤ 120 mmol/L who were admitted to 2 large teaching hospitals from January 2000 to August 2007 were identified, and data were obtained from medical records. Main outcome measures were incidence of osmotic demyelination and mortality. RESULTS: Two hundred fifty-five patients were admitted who had SHH (female to male ratio 2:1), and the mean age was 72 ± 14 years. The most common etiological factors were thiazide/indapamide diuretics (41%), syndrome of inappropriate antidiuretic hormone secretion (38%), and hypovolemia (24%). Inappropriately rapid correction of serum sodium (> 12 mmol/L over the first 24 hours) occurred in 37 patients (15%), with 4 patients (11%) developing osmotic demyelination. Patients who developed osmotic demyelination were more likely to be younger, abuse alcohol (3 of 4 patients), and have lower serum potassium levels. One patient had a hypoxic-anoxic episode at presentation. The patients also had a mean serum sodium increase in the first 24 and 48 hours of 21 ± 5 mmol/L and 28 ± 8 mmol/L, respectively. None of the patients with osmotic demyelination received hypertonic saline. None of the patients in whom the serum sodium increment was limited to ≤ 12 mmol/L developed osmotic demyelination. Overall, mortality was 10% and was not related to sodium level at presentation. CONCLUSIONS: Patients treated with thiazide or indapamide (particularly elderly women) may benefit from monitoring of serum sodium levels. Inappropriately rapid serum sodium correction is associated with osmotic demyelination, particularly in patients with risk factors for this condition. In contrast to what has been reported for hyponatremia in hospitalized patients, severity of hyponatremia on admission did not predict increased mortality in our patient population.

Gonadotroph adenoma in multiple endocrine neoplasia type 1.

OBJECTIVE: To describe a case of an in vivo follicle-stimulating hormone (FSH)-secreting gonadotroph adenoma in a man with multiple endocrine neoplasia type 1 (MEN 1) syndrome. METHODS: We present a retrospective case description and a discussion of the related literature. RESULTS: A 48-year-old man had progressively deteriorating visual acuity and bitemporal hemianopia, found to be attributable to a macroadenoma encircling both carotid arteries and compressing the optic chiasm. His libido and erectile function had been reduced for 2 years. The serum FSH level was substantially elevated at 31.1 IU/L (reference range, 1 to 10); alpha-subunit was elevated at 2.25 IU/L (reference range, 0.09 to 0.4); luteinizing hormone was normal at 4 IU/L (reference range, 1 to 10); total testosterone was low at 6.8 nmol/L (reference range, 9.5 to 35); and prolactin was slightly increased at 433 mU/L (reference range, 50 to 300). Transsphenoidal hypophysectomy was performed. Pituitary histopathologic examination showed a tumor with cytoplasmic granular FSH immunoreactivity. The patient had undergone parathyroidectomy for primary hyperparathyroidism 2 years before the current intervention. A family history of endocrine neoplasia was obtained of one sibling with a nonfunctioning pituitary adenoma, another sibling who had died of pancreatic carcinoma, and a third sibling, along with her son, who has primary hyperparathyroidism. Performance of genetic testing for MEN 1 revealed a nonsense mutation--R460X (nt7605C>T)--located on exon 10 of the MEN1 gene. CONCLUSION: We report an unusual case of clearly high circulating immunoreactive FSH due to a functioning FSH-secreting gonadotroph adenoma in a man with the MEN 1 syndrome.

Emergency vaccination of sheep against foot-and-mouth disease: significance and detection of subsequent sub-clinical infection.

This study has quantified the level of foot-and-mouth disease virus (FMDV) replication and shedding in vaccinated sheep and correlated this to the severity of clinical signs, the induction of antibodies against FMDV non-structural proteins (NSPs) and the transmission of virus to in-contact vaccinated sentinel sheep. To mimic an emergency vaccination regime in the field, sheep were vaccinated with O(1) Manisa vaccine and 4 or 10 days later were indirectly challenged with aerosols from O(1) UKG FMDV infected pigs. Vaccinated and control unvaccinated sheep were monitored for a minimum of 39 days post-challenge. The vaccinated sheep became sub-clinically infected, with reduced virus replication and excretion compared to unvaccinated and clinically infected sheep. Seroconversion to NSP was weak and transient in sheep in which virus replication was of low level and short duration. Virus transmission from vaccinated sub-clinically infected sheep to introduced vaccinated sentinels was not sufficient to cause NSP seroconversion or significant virus shedding. 10% of 10 days and 20% of 4 days vaccinated sheep were virus carriers at greater than 28 days post-challenge compared to 37.5% in the unvaccinated and clinically infected sheep. These results suggest that the low levels of virus replication likely if an effective vaccine is administered at least 4 days prior to challenge exposure are unlikely to result in the spread of infection even under intensive management conditions. Although it may be difficult to detect this infection by serosurveillance, the significance of missing it is likely to be low and the main value of such testing will be to detect undisclosed clinical infection resulting from lack of observation or from exposure to virus before or very soon after vaccination or from vaccine failure due to maladministration or inappropriate strain selection.

Serological survey for foot-and-mouth disease virus in wildlife in eastern Africa and estimation of test parameters of a nonstructural protein enzyme-linked immunosorbent assay for buffalo.

In this study we estimate the seroprevalence of foot-and-mouth disease virus (FMDV) in wildlife from eastern and central Africa. Sera were sourced from between 1994 and 2002 from a rinderpest surveillance program. Our study compared a nonstructural protein enzyme-linked immunosorbent assay (Cedi test) with a virus neutralization test. The study shows that there is only a low seroprevalence of FMDV in sampled nonbuffalo species. The seroprevalence in the Cape buffalo was high for SAT2, lower for SAT1, and lowest for SAT3. As the SAT2 serotype was most prevalent, the Cedi test largely reflected the occurrence of SAT2-positive animals. The results also suggest that SAT2 became dominant around 1998, with a large increase in seroprevalence. The sensitivity and specificity of the Cedi test were estimated by comparison to the combined virus neutralization test results from all three SAT tests. A Bayesian implementation of the Hui-Walter latent class model was used to estimate the test parameters. The model permits estimation in the absence of a gold standard test. The final model, using noninformative priors and assuming conditional independence of test performance, estimated Cedi test sensitivity at 87.7% and specificity at 87.3%. These estimates are similar to those for domestic bovines; they suggest that the Cedi test is a useful tool for screening buffalo for infection with the various serotypes of FMDV.

Reduction of foot-and-mouth disease (FMD) virus load in nasal excretions, saliva and exhaled air of vaccinated pigs following direct contact challenge.

In future, a policy of "vaccinate-to-live" may be included in the repertoire of foot-and-mouth disease (FMD) control measures and in support of this approach, we have investigated the hypothesis that vaccine-induced reduction in virus replication and excretion from pigs can be correlated to the severity of clinical signs of FMD by measuring excretion of virus in natural secretions and aerosols. The other aims of this study were to verify the existence of sub-clinical infection in vaccinated pigs, to evaluate the correlation between this and seroconversion to foot-and-mouth disease virus (FMDV) non-structural protein antibodies and to re-examine the occurrence of FMDV persistence in the oro-pharynx of pigs. Therefore, pigs were vaccinated (O1 Manisa) and challenged (O1 UKG) in a manner calculated to produce a broad range of clinical outcomes and were monitored for a minimum of another 33 days post-challenge. Eighty-one percent of the early (10 days vaccinated) challenged pigs and 25% of the late (29 days vaccinated) challenged pigs were clinically infected and all other vaccinated pigs were sub-clinically infected. Although vaccination could not provide complete clinical or virological protection, it reduced the severity of the disease, virus excretion and production of non-structural FMDV antibodies in vaccinated and subsequently infected pigs. As hypothesised, vaccine-induced reduction of virus replication and excretion was found to be correlated to the severity of clinical disease. RNA copies, but no live virus was detected from the pharyngeal and soft palate tissues of a minority of vaccinated and infected pigs beyond the acute stage of the infection.

Evaluation of laboratory tests for SAT serotypes of foot-and-mouth disease virus with specimens collected from convalescent cattle in Zimbabwe.

During a field study in Zimbabwe, clinical specimens were collected from 403 cattle in six herds, in which the history of foot-and-mouth disease (FMD) vaccination and infection appeared to be known with some certainty. Five herds had reported outbreaks of disease one to five months previously but clinical FMD had not been observed in the sixth herd. A trivalent vaccine (South African Territories [SAT] types 1, 2 and 3) had been used in some of the herds at various times either before and/or after the recent outbreaks of FMD. The primary aim of this study was to evaluate the performance of serological tests for the detection of SAT-type FMD virus infection, particularly elisas for antibodies to non-structural proteins (NSPs) of FMD virus and solid phase competition ELISAS (SPCEs) for serotypes SAT1 and SAT2. Secondary aims were to examine NSP seroconversion rates in cattle that had been exposed to infection and to compare virus detection rates by virus isolation and real-time reverse transcriptase-PCR (rtRT-PCR) tests on both oesophagopharyngeal fluids and nasopharyngeal brush swabbings. In addition, the hooves of sampled animals were examined for growth arrest lines as clinical evidence of FMD convalescence. Laboratory tests provided evidence of FMD virus infection in all six herds; SAT2 viruses were isolated from oesophagopharyngeal fluids collected from two herds in northern Zimbabwe, and SAT1 viruses were isolated from three herds in southern Zimbabwe. Optimised rtRT-PCR was more sensitive than virus isolation at detecting FMD virus persistence and when the results of the two methods were combined for oesophagopharyngeal fluids, between 12 and 35 per cent of the cattle sampled in the convalescent herds were deemed to be carriers. In contrast, nasopharyngeal swabs yielded only two virus-positive specimens. The overall seroprevalence in the five affected herds varied with the different NSPS from 56 per cent to 75 per cent, compared with 81 per cent and 91 per cent by homologous SPCE and virus neutralisation tests respectively. However, if serological test results were considered only for the cattle in which persistent infection with FMD virus had been demonstrated, 70 to 90 per cent scored seropositive in the different NSPs.

Geographical and age-stratified distributions of foot-and-mouth disease virus-seropositive and probang-positive cattle herds in the Adamawa province of Cameroon.

Six of the seven known serotypes of foot-and-mouth disease (FMD) virus occur in Africa. This paper describes the results of a population-based cross-sectional study of the seroprevalence of FMD and the persistence of the virus in cattle herds and associated sheep flocks in the Adamawa province of Cameroon. Antibody titres measured by the virus neutralising test indicated that serotypes O, A and SAT2 viruses had been circulating in the province. The estimates of apparent seroprevalence in cattle herds, based on five juvenile animals (eight to 24 months old) per herd, were 74.8 per cent for serotype SAT2, 30.8 per cent for serotype A and 11.2 per cent for serotype O, indicating recent exposure; the estimates based on animals more than 24 months of age were 91.1 per cent for SAT2, 83.6 per cent for A and 34.2 per cent for serotype O. Epithelial and oropharyngeal samples were collected from cattle and small ruminants, cultured and typed by ELISA; serotypes A and SAT2 were isolated from both types of sample. The herd-level estimate of apparent prevalence of probang-positive herds was 19.5 per cent and the animal-level estimate of apparent prevalence was 3.4 per cent. The geographical distribution of the seropositive herds based on juveniles suggested that recent SAT2 exposure was widespread and particularly high in the more northern and western parts of the province, whereas recent exposure to serotype A was patchy and more concentrated in the south and east. This distribution corresponded very closely with the distribution of herds from which virus was recovered by probang, indicating recent exposure or infection. No serotype O viruses were recovered from cattle, and the distribution of seropositive herds suggested very localised recent exposure. The apparent prevalence of probang-positive animals declined with the age of the animal and the period since the last recorded outbreak in the herd.

Effect of emergency FMD vaccine antigen payload on protection, sub-clinical infection and persistence following direct contact challenge of cattle.

Previous work, in sheep vaccinated with emergency foot-and-mouth disease (FMD) vaccine, indicated the benefit of increasing the antigen payload in inhibiting local virus replication and consequently persistence following an indirect aerosol challenge with a virus homologous to the vaccine strain. The work presented here investigates this possibility further using cattle and a more severe semi-heterologous direct contact challenge. The quantitative dynamics of virus replication and excretion in both vaccinated and non-vaccinated cattle following challenge are examined. Two experiments were carried out each involving 20 vaccinated and 5 non-vaccinated cattle. An O(1) Manisa vaccine (18 PD(50)) was used for the first, previously reported experiment [Cox SJ, Voyce C, Parida S, Reid SM, Hamblin PA, Paton DJ, et al. Protection against direct contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx. Vaccine 2005;23:1106-13]. The same vaccine was used for the second experiment described in this paper except the antigen payload was increased 10-fold per bovine dose, resulting in significantly higher FMD virus neutralising antibody titres prior to challenge. Twenty-one days post-vaccination the cattle received a 5-day direct contact challenge with FMD virus from five further non-vaccinated cattle infected 24h earlier with O UKG 34/2001. All vaccinated cattle regardless of antigen payload were protected against clinical disease. Sub-clinical oropharyngeal infection was detected in animals from both experiments but the level of virus replication shortly after direct contact challenge was significantly reduced in vaccinated animals. Cattle immunised with the 10-fold antigen payload cleared the virus more readily and consequently at 28 days post-challenge fewer animals were persistently infected compared to the single strength vaccine. Following a severe challenge, the results from both experiments show that use of emergency vaccine can prevent or decrease local virus replication and thereby dramatically reduce the amount of virus released into the environment, particularly during the early post-exposure period. Additionally, increasing the antigen payload of the vaccine may reduce sub-clinical infection, leading to fewer persistently infected virus carrier animals.

Immunity induced by the radiation-attenuated schistosome vaccine.

As a paradigm for the development of a vaccine against human schistosomiasis, the radiation-attenuated (RA) vaccine has enabled the dissection of different immune responses as putative effector mechanisms. This review considers advances made in the past, and updates our knowledge with reference to recent studies that have provided new information relevant particularly to the early innate events after vaccination, and to the nature of the protective effector mechanism. Priming of a protective response by RA larvae is a highly co-ordinated series of events starting in the skin, draining lymph nodes and lungs, leading to the development of various effector responses, ranging from Th1-associated cell-mediated activity, to anti-parasitic antibodies, all of which contribute to the elimination of challenge larvae to varying extents. In this respect, the RA vaccine elicits a multifaceted immune response, from which we can derive valuable insights relevant to the future design of novel delivery systems and adjuvants for recombinant and subunit vaccines.