A randomised controlled trial of SMS messaging and calendar reminders to improve vaccination timeliness in infants.

BACKGROUND: The effectiveness of SMS reminders in improving vaccination coverage has been assessed previously, with effectiveness varying between settings. However, there are very few studies on their effect on the timeliness of vaccination. DESIGN: Unblinded, randomised controlled trial with blocked sampling. METHODS: 1594 Australian infants and young children were recruited to assess the impact of (1) SMS reminders only, (2) a personalised calendar, (3) SMS reminder and personalised calendar and (4) no intervention, on receipt of vaccine within 30 days of the due date. Outcomes were measured for receipt of vaccines due at 2, 4, 6, 12 and 18 months of age. A post-hoc assessment was also conducted of the impact of a new national "No jab No Pay" policy introduced during the trial, which removed philosophical objections as an exemption for financial penalties for non-vaccination. RESULTS: There was a statistically significant improvement in on-time vaccination only at the 12 month schedule point amongst infants who received SMS reminders alone (RR 1.09, 95% CI 1.01-1.18) or in combination with a personalised calendar (1.11, CI 1.03-1.20) compared to controls. This impact was limited to participants who had received one or more previous doses late. No statistically significant impacts of calendar interventions alone were seen. There was a high rate of on-time compliance amongst control participants - 95%, 86%, 80%, 74% at the 4, 6, 12 and 18 month schedule points respectively, which increased more than 10 percentage points after implementation of the "No Jab, No Pay" policy. CONCLUSIONS: SMS reminders are more effective in improving timeliness where pre-existing compliance is lower, but the 18 month schedule point appeared to be less amenable to intervention. Australia and New Zealand Clinical Trial Registration No. ACTRN12614000970640.

Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before, with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial.

Hajj pilgrims are susceptible to several serious infections and are required to receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate or combination vaccines containing tetanus or diphtheria on concurrent or sequential administration. We examined the immune interaction of separate and concomitant administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with 13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian pilgrims before attending Hajj in 2015. We randomly assigned each participant to one of three vaccination schedules. Group 1 received Tdap 3-4 weeks before receiving MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly. Group 3 received MCV4 and PCV13 3-4 weeks before Tdap. Blood samples were collected at baseline, at each vaccination visit and 3-4 weeks after vaccination and tested for response to meningococcal serogroups C, W and Y using a serum bactericidal antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries after each vaccination. A total of 166 participants aged 18-64 (median 42) years were recruited, of whom 160 completed the study. Compared to the other groups, Group 1 (given Tdap first) had significantly lower proportion of subjects achieving a ≥4-fold rise in rSBA for serogroup W. No difference was detected across the three groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric mean titre (GMT) post vaccination. Group 3, which was given MCV4/PCV13 first, had high levels of antibody against diphtheria and tetanus than the other groups, when tested prior to receipt of Tdap; Only the anti-tetanus responses remained significantly higher after Tdap administration. No serious adverse events were reported. In conclusion, when multiple vaccination is required for Hajj pilgrims, administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses, and avoids meningococcal immune interference, in the convenience of a single consultation. However, giving Tdap 3-4 weeks after MCV4/PCV13 has the advantage of an enhanced tetanus toxoid response. The trial is Trials Registry (ANZCTR): ACTRN12613000536763.

Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.

Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse events were reported. In conclusion, Tdap vaccination 3-4weeks before concomitant administration of PCV13 and MCV4 significantly reduced the antibody response to six of the 13 pneumococcal serotypes in adults. The trial is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000536763.

Alcohol Dependence, Co-occurring Conditions and Attributable Burden.

AIMS: Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. METHODS: A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. RESULTS: Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. CONCLUSIONS: Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care.

Elicitation of health state utilities associated with differing durations of morning stiffness in rheumatoid arthritis.

OBJECTIVE: Specific symptoms of rheumatoid arthritis (RA), including joint stiffness and functional disability, are most severe in the morning. 'Morning stiffness' has a negative impact on health-related quality-of-life (HRQoL); however, how HRQoL is correlated to morning stiffness duration is unknown. The objective of this study was to obtain population-based utility values associated with different durations of morning stiffness in RA. DESIGN AND METHODS: The time-trade-off (TTO) approach was used to elicit utility values for four different health states (HS), which differed in morning stiffness duration. One hundred and nine members of the UK general public rated each HS in individual face-to-face interviews with trained investigators. TTO scores were converted into utility values. Visual Analog Scale (VAS) scores were obtained to validate TTO scores. RESULTS: On a scale of 0 (death) to 1 (full health), a mean utility value of 0.45±0.29 was elicited for ∼3 h of morning stiffness (anchor HS), 0.50±0.28 for 2-3 h of morning stiffness (HS1), 0.61±0.25 for 1-2 h of morning stiffness (HS2) and 0.78±0.20 for <1 h of morning stiffness (HS3). The difference between each HS was statistically significant (p<0.01). Mean VAS utility scores followed the same trend. Utility incrementally increased with each HS associated with a shorter duration of morning stiffness. Limitations of this research include potential bias from the TTO method due to the discounting effect of time, scale compatibility, and loss aversion. CONCLUSIONS: The UK population-based utility values show a reduction in morning stiffness duration in RA is associated with improved HRQoL. Despite the impact of morning stiffness on HRQoL, it is rarely evaluated and little is known as to how it is affected by current treatments. The results of this study can be applied in future cost-utility analyses of healthcare interventions which target an improvement in morning stiffness duration for RA patients.

The burden of infectious gastroenteritis in elderly residents and staff of long-term care facilities, Australia.

We estimated the incidence of gastroenteritis in 16 Australian long-term care facilities. During 12 months' surveillance, 245 (96%) of 254 episodes of gastroenteritis among long-term care residents were associated with 17 outbreaks in 11 facilities. Incidence in long-term care residents was 0.64 episodes per 1,000 bed-days (95% confidence interval, 0.29-1.42).

A boarding school outbreak of pertussis in adolescents: value of laboratory diagnostic methods.

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P < 0.001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.

A statewide outbreak of cryptosporidiosis in New South Wales associated with swimming at public pools.

From December 1997 to April 1998, 1060 laboratory-confirmed cryptosporidiosis cases were reported in New South Wales, Australia. In a case-control study, compared with 200 controls, the 100 cases were younger (mean age 42 versus 71 years; P < 0.0001), more likely to report swimming at a public pool (59% versus 38%; adjusted OR and 95% CI = 27; 1.4-5.1) and swimming in a dam, river or lake (OR = 48; 1.1-20.3) but less likely to report drinking bottled water (OR = 0.4; 0.2-0.9). In subgroup analyses, in rural areas illness was associated mainly with contact with another person with diarrhoea, and in urban areas illness was associated with swimming in a public pool. Cryptosporidium oocysts were more commonly detected in pools to which at least two notified cases had swum (P = 004). Outbreaks of cryptosporidiosis can be prolonged, involve multiple pools and be difficult to control.

Group B streptococcus screening in pregnant women: a comparison of three media.

This study compared the relative isolation rate of Group B Streptococcus (GBS) from 663 low vaginal swabs, collected from antenatal patients, on three media: horse blood agar plus neomycin (75 mg/l) (Neo), Islam agar (Islam) and Islam agar plus nalidixic acid (15 mg/l) and colistin sulphate (10 mg/l) (Islam Plus). One hundred and forty-seven (22%) GBS were isolated. At 24 hours the isolation rate was highest using Neo, but within 72 hours there was little difference. The isolation rates for Neo, Islam and Islam Plus at 24 hours were 124 (18.7%), 103 (15.6%), 109 (16.4%) (P < 0.05); at 48 hours 125 (18.9%), 116 (17.5%), 121 (18.1%) (P > 0.1); and at 72 hours 125 (18.9%), 121 (18.3%) and 127 (19.1%) (P > 0.1), respectively. Twenty-two isolates were missed on Neo, 26 on Islam and 20 on Islam Plus. Of those missed on Islam agars, 12 failed to produce pigment and were only detected on Neo. The disadvantage of Neo is the need to perform additional tests to confirm the identity as GBS. In the present study 100 suspicious colonies were identified as Group D.

Isolation, characterization, and chromosomal localization of the human ENSA gene that encodes alpha-endosulfine, a regulator of beta-cell K(ATP) channels.

Human alpha-endosulfine is an endogenous regulator of the beta-cell K(ATP) channels. The recombinant alpha-endosulfine inhibits sulfonylurea binding to beta-cell membranes, reduces cloned K(ATP) channel currents, and stimulates insulin secretion from beta-cells. These properties led us to study the human ENSA gene that encodes alpha-endosulfine. Here, we describe the isolation, the partial characterization, and the chromosomal localization of the ENSA gene. The ENSA gene appears to be a 1.8-kb-long sequence that contains the transcription initiation site located 528 bp upstream of the initiation codon. The ENSA gene is intronless, and a single copy gene seems to be present in the genome. Finally, the ENSA gene co-localizes on human chromosome 14 (14q24.3-q31) with a locus for susceptibility to type 1 diabetes called IDDM11; thus, the ENSA gene represents an IDDM11 candidate.

alpha-Endosulfine, a new entity in the control of insulin secretion.

ATP-dependent potassium (K ATP) channels occupy a key position in the control of insulin release from the pancreatic beta cell since they couple cell polarity to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion from beta cells that have lost part of their sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called 'endosulfines.' In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass form, alpha-endosulfine, and discuss its possible role in the physiology of the beta cell as well as in pathology.

Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel: molecular cloning, expression and biological properties.

Sulfonylureas are a class of drugs commonly used in the management of non-insulin-dependent diabetes mellitus. Their therapeutic action results primarily from their ability to inhibit ATP-sensitive potassium (KATP) channels in the plasma membrane of pancreatic beta cells and thereby stimulate insulin release. A key question is whether an endogenous ligand for the KATP channel exists that is able to mimic the inhibitory effects of sulfonylureas. We describe here the cloning of the cDNA encoding human alpha-endosulfine, a 13-kDa peptide that is a putative candidate for such a role. alpha-Endosulfine is expressed in a wide range of tissues including muscle, brain, and endocrine tissues. The recombinant protein displaces binding of the sulfonylurea [3H]glibenclamide to beta cell membranes, inhibits cloned KATP channel currents, and stimulates insulin secretion. We propose that endosulfine is an endogenous regulator of the KATP channel, which has a key role in the control of insulin release and, more generally, couples cell metabolism to electrical activity.

Effect on organism recovery rate from BacT/Alert blood cultures with reduced incubation period.

This retrospective study evaluated 15,377 sets of BacT/Alert blood cultures to determine incubation time for blood cultures. Ninety-six per cent (1476) of total isolates signalled positive within five days and 56 isolates turned positive in five to seven days. Of the 56 organisms recovered between five and seven days, 49 were considered contaminants and seven were considered clinically significant. On assessing the medical records of the patients with the seven clinically significant isolates, it was determined that the clinical outcome would not have changed if these isolates were missed. We conclude that a five day incubation protocol reduces the recovery of skin contaminants while not significantly decreasing the recovery of clinically significant organisms. The data suggest that the incubation time can be further reduced but this policy will depend on the individual institution and their patient population mix.

Leptospirosis presenting as a haemorrhagic fever in a traveller from Africa.

Leptospirosis is usually a mild illness, although the severity of clinical manifestations may vary between the serovars of leptospires. In May 1993, a 48-year-old man from Ghana presented with severe icteric leptospirosis, initially managed as viral haemorrhagic fever. The causative serovar, bataviae, had not been previously diagnosed in human infection in Australia.

Alpha endosulfine is a novel molecule, structurally related to a family of phosphoproteins.

We have observed that alpha endosulfine, the 13KDa form of the endogenous ligand for sulfonylurea receptor recently isolated from porcine brain, displays strong similarities with a phosphoprotein of similar size previously isolated from bovine brain and called ARPP-19. To determine whether the two proteins are different entities, we developed an RT-PCR strategy for analyzing the main portion of bovine alpha endosulfine. We show that alpha endosulfine and ARPP-19 are different entities from the same family of proteins, coded by distinct genes.

An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line.

mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription. This antiviral effect requires the integrity of the cytoplasmic tail of CD4, which acts as a signal transduction region through its association with protein tyrosine kinases such as p56Ick. Here we investigated the role of p56Ick in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig CDR3-like region. The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56Ick-negative HTLV-I-producing MT2 cells superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it did inhibit Tax-induced NF-kappa B translocation. These results raise the possibility that an as yet unidentified tyrosine kinase may be capable of associating with CD4 and mediating intracellular signaling.

Paecilomyces variotii in peritoneal dialysate.

Four cases of peritonitis caused by the filamentous fungus Paecilomyces variotii in patients on continuous ambulatory peritoneal dialysis are reported. Removal of the Tenckhoff catheter and antifungal chemotherapy led to resolution of symptoms in all cases. Possible contaminating events are discussed, and reported infections with P. variotii are reviewed.

Infective endocarditis due to nontoxigenic Corynebacterium diphtheriae: report of seven cases and review.

We report seven cases of endocarditis due to nontoxigenic Corynebacterium diphtheriae that occurred between October 1990 and September 1991. The patients all lived in the state of New South Wales, Australia. Three patients had preexisting cardiac abnormalities, and one patient used intravenous drugs regularly. The other three patients had no known risk factors for endocarditis. Notable clinical features were the aggressive nature of the infection, the occurrence of septic arthritis in four patients, and major vascular complications in four patients, one of whom died. One patient required urgent mitral valve replacement. All of the isolates were identified as non-toxigenic C. diphtheriae var gravis. Sporadic cases of endocarditis due to C. diphtheriae have rarely been reported; septic arthritis complicating endocarditis due to this organism has not previously been described. This report highlights the importance of identifying Corynebacterium isolates from normally sterile sites at the species level.