High burden of invasive group A streptococcal disease in the Northern Territory of Australia.

Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response.

Pitch Memory in Nonmusicians and Musicians: Revealing Functional Differences Using Transcranial Direct Current Stimulation.

For music and language processing, memory for relative pitches is highly important. Functional imaging studies have shown activation of a complex neural system for pitch memory. One region that has been shown to be causally involved in the process for nonmusicians is the supramarginal gyrus (SMG). The present study aims at replicating this finding and at further examining the role of the SMG for pitch memory in musicians. Nonmusicians and musicians received cathodal transcranial direct current stimulation (tDCS) over the left SMG, right SMG, or sham stimulation, while completing a pitch recognition, pitch recall, and visual memory task. Cathodal tDCS over the left SMG led to a significant decrease in performance on both pitch memory tasks in nonmusicians. In musicians, cathodal stimulation over the left SMG had no effect, but stimulation over the right SMG impaired performance on the recognition task only. Furthermore, the results show a more pronounced deterioration effect for longer pitch sequences indicating that the SMG is involved in maintaining higher memory load. No stimulation effect was found in both groups on the visual control task. These findings provide evidence for a causal distinction of the left and right SMG function in musicians and nonmusicians.

Molecular characterization of an Australian serotype 1 Streptococcus pneumoniae outbreak.

Serotype 1 Streptococcus pneumoniae is a cause of invasive pneumococcal disease (IPD) worldwide and has been associated with IPD outbreaks, while carriage is rarely detected in healthy adults or children. This study details an Australian multi-state and territory outbreak of serotype 1 S. pneumoniae IPD between 2010 and 2012. Molecular characterization demonstrated the outbreak was largely due to the clonal expansion of sequence type 306, MLVA type 261 S. pneumoniae serotype 1.

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Motor-cortical oscillations in early stages of Parkinson's disease.

Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug­naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13­30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest. The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD.

Multidrug-resistant tuberculosis in Australia, 1998-2012.

OBJECTIVE: To describe the epidemiology and outcomes of multidrug-resistant tuberculosis (MDR-TB) diagnosed in Australia between 1998 and 2012. DESIGN: A retrospective review was undertaken involving all patients with laboratory-confirmed MDR-TB notified in Australia between 1998 and 2012 inclusive. Demographic, clinical and laboratory features are described. Clinical outcomes were defined according to World Health Organization definitions of treatment success (cure and treatment completion), treatment failure, death, loss to follow-up (including transfer out), or not evaluated at treatment completion. RESULTS: A total of 244 cases of MDR-TB were diagnosed in Australia during the study period, representing 1.4% of all TB cases notified. The majority were born outside Australia, including one third in Papua New Guinea. Of those with treatment outcome data available, treatment success was demonstrated in 81%. Treatment success was positively associated with use of a second-line injectable agent. Those born in Papua New Guinea were less likely to achieve treatment success. CONCLUSION: MDR-TB is uncommon in Australia. The large number of cases born in Papua New Guinea, and the poorer outcomes in this cohort, represent challenges with cross-border management of MDR-TB in the Torres Strait. Australia has an ongoing role in the prevention and management of MDR-TB locally and in the region.

Transcranial direct current stimulation (tDCS) applied to the left dorsolateral premotor cortex (dPMC) interferes with rhythm reproduction.

Movement timing in the sub-second range engages a brain network comprising cortical and sub-cortical areas. The present study aims at investigating the functional significance of the left dorsolateral premotor cortex (dPMC) for precise movement timing as determined by sensorimotor synchronization and rhythm reproduction. To this end, 18 healthy volunteers performed an auditorily paced synchronization-continuation task with the right hand. A simple reaction time task served as control condition. Transcranial direct current stimulation (tDCS) was applied over the left dPMC in order to modulate cortical excitability either with anodal or cathodal polarity or as sham stimulation. TDCS was applied for 10 minutes, respectively on separate days. For the continuation task the analysis revealed significantly smaller inter-tap intervals (ITIs) following cathodal tDCS suggesting movement hastening as well as a trend towards larger ITIs following anodal stimulation suggesting movement slowing. No significant effect was found following sham stimulation. Neither for synchronization nor for reaction time tasks significant polarity-specific effects emerged. The data suggest the causal involvement of the dPMC in temporally precisereproduction of isochronous rhythms rather than sensorimotor synchronization. The present findings support the hypothesis that different cortical brain areas within the motor-control-network distinctively contribute to movement timing in the sub-second range.

Seroprevalence of Burkholderia pseudomallei in East Timorese refugees: implications for healthcare in East Timor.

Melioidosis is a disease with protean clinical manifestations caused by the bacterium Burkholderia pseudomallei. It is endemic in countries surrounding the newly independent East Timor, but has yet to be isolated or demonstrated serologically in that country. One illness that can be clinically indistinguishable from melioidosis is pulmonary tuberculosis, a condition with a very high prevalence in East Timor. We used an indirect hemagglutination test (IHA) to measure antibodies to B. pseudomallei in 407 East Timorese evacuated to Darwin, Australia, in September 1999. Assuming a positive IHA titer as > or = 1:40, the overall seroprevalence rate was 17.0%, in keeping with other seroprevalence studies from the region. The IHA titres ranged up to 1:320. After adjusting for age, females were 2.5 times more likely to be seropositive than males (p = 0.0001). There was an inverse relationship between seropositivity and age. This study shows that exposure to B. pseudomallei occurs in East Timor melioidosis is also likely to occur. Due to the lack of laboratory facilities at present, it may be some time before a laboratory-confirmed case proves that melioidosis occurs. In the meantime, clinicians in East Timor should include melioidosis in the differential diagnosis of the many conditions that it may mimic.

Improved cell surface radioiodination of macrophages.

Rabbit alveolar macrophages at high cell concentrations are inefficiently radiolabeled by the usual lactoperoxidase-catalyzed iodination method. Soluble macromolecules secreted by macrophages were found to inhibit the radioiodination of macrophages and other cells. A modified procedure is described which minimizes the presence of such inhibitory material and thereby considerably improves the radioiodination efficiency for both alveolar macrophages and the macrophage-like P388D1 cell line.

Success of a scabies control program in an Australian aboriginal community.

OBJECTIVE: To adapt, implement and evaluate a model of scabies control in an Australian Aboriginal community. METHODS: After initially examining the population, we offered all residents treatment with 5% permethrin cream. Visits were made during the ensuing 25 months to rescreen and to treat new-cases of scabies and contacts. RESULTS: The prevalence of scabies was reduced from 28.8% before the program to < 10% during the entire period (from 32.3% to < 10% in children) (P < 0.01 for each visit). The initial prevalence of pyoderma in children was 69.4%, which was reduced and maintained at approximately one-half that rate during the last 16 months (P < 0.004 for the last 4 visits). Residual pyoderma in children was significantly less severe and no longer scabies-related. CONCLUSIONS: This simplified model of scabies control had a substantial effect on scabies prevalence and on pyoderma prevalence and severity which was sustained for > 2 years. It could prove useful for other communities with high rates of scabies and pyoderma.

Placental infection with Mycoplasma homonis and Ureaplasma urealyticum: clinical correlation.

Placentas from a clinical study group of 446 high-risk pregnancies and 108 normal pregnancies were cultured for Mycoplasma hominis and Ureaplasma urealyticum and examined histologically. Results were compared and correlated with the clinical history. The recovery rate of U urealyticum, but not of M hominis, was significantly higher in the clinical study than in the control group. Isolation of both mycoplasmas was associated with polymorphonuclear leukocyte infiltration of placental membranes, fetal surface, and umbilical cord. Recovery of mycoplasma was significantly higher with prolonged membrane rupture, spontaneous abortion, stillbirth, and early neonatal death. Isolation of U urealyticum, but not of M hominis, was associated with prematurity, lower birth weight, and intrauterine growth retardation.

Restriction endonuclease digestion analysis of DNA from viruses isolated from different sites of two fatal cases of herpes simplex virus type-1 infection.

Herpes simplex virus (HSV) type-1 was isolated from a fatal case of herpes simplex encephalitis (case 1) and from a fatal case of disseminated herpes simplex (case 2). The virus was isolated from the lip lesion, the frontal lobe and the temporal lobe of the brain in case 1 and from a mesenteric node, myocardium and salivary gland in case 2. Restriction endonuclease digestion analysis showed that each case was infected with different substrains of HSV. The changes in band pattern in isolates from case 1 occurred in the "variable" region of the genome, showing that viruses with such variations can be isolated simultaneously from different tissues. The changes in band patterns in isolates from case 2 indicated the presence of two virus substrains, one in the mesenteric node and salivary gland and a second in the myocardium.

Tuberculosis in east timorese refugees: implications for health care needs in East Timor.

SETTING: East Timorese refugees evacuated to Darwin, Australia, September 1999. OBJECTIVE: Presentation of the process and results of tuberculosis (TB) screening in a previously unscreened refugee population. DESIGN: Screening for TB by clinical examination (all persons) and chest X-ray (CXR) (persons over 12 years of age and those of any age with respiratory symptoms) and sputum microscopy and mycobacterial culture (abnormal CXR). RESULTS: Seventy-six patients were diagnosed with TB (38 culture-positive for Mycobacterium tuberculosis, including 11 sputum smear-positive). Of 89 positive mycobacterial cultures, 51 were non-tuberculous mycobacteria (NTM). Of the M. tuberculosis isolates, 82.2% were fully sensitive, 17.2% were resistant to isoniazid and 8.6% were resistant to isoniazid and streptomycin. Fifty-three consecutively diagnosed patients with TB were HIV-negative. The TB burden in this population was very high (point prevalence of 542/100,000 for smear-positive and 2,060/100,000 for culture-positive cases). Rates of culture for NTM were also high. Information from this study assisted the implementation of a National TB Control Programme for East Timor in February 2000. CONCLUSION: The challenges for public health authorities in East Timor to provide a successful TB control programme are enormous. The apparently low prevalence of drug resistance and HIV co-infection in the population is encouraging.

Functional magnetic resonance imaging of the human cervical spinal cord with stimulation of different sensory dermatomes.

Functional MR imaging (fMRI) of the cervical spinal cord was carried out in 13 healthy volunteers. A cold stimulus was applied, at different times, to three different sensory dermatome regions overlying the right hand and forearm: the thumb side of the palm, the little finger side of the palm, and the forearm below the elbow. Stimulation of these areas is expected to involve the 6(th), 8(th), and 5(th) cervical spinal cord segments respectively. Whereas true activations are expected to correspond to the region being stimulated, false activations such as arising from noise and motion, are not. The results demonstrate that clustering of active pixels into groups based on their intensity time courses discriminates false activations from true activations. Following clustering, the distribution of activity observed with fMRI matched the expected regions of neuronal activation with the different areas of stimulation on the hand and forearm.

Spin-echo versus gradient-echo fMRI with short echo times.

Blood-oxygen level dependent signal changes in the visual cortex were investigated as a function of echo time with spin-echo and gradient-echo EPI at 1.5 T and 3 T. The linear relationship between the fractional signal change and the echo time was apparent in all cases. Relaxation rate changes determined from the slope of this linear relation agree with published values, intercept values extrapolated to an echo time of zero, however, were 0.66% to 1.0% with spin-echo EPI, and 0.11% to 0.35% with gradient-echo EPI. Spin-echo and gradient-echo EPI can therefore yield similar signal changes at sufficiently short echo times.

Characterization of contrast changes in functional MRI of the human spinal cord at 1.5 T.

Contrast changes observed in functional magnetic resonance imaging in the human spinal cord were investigated with both motor and sensory tasks over a range of echo times. Data were acquired using a single-shot fast spin-echo sequence at 1.5 Tesla. Data were analyzed with two different correlation thresholds and the effects of altering the order of repeated experiments was also investigated. Plots of the fractional signal change as a function of echo time yielded linear functions with slopes corresponding to relaxation rate changes of -0.30 sec(-1) with sensory stimulation and approximately -0.50 sec(-1) with a motor task. However, the fractional signal change extrapolated to an echo time of zero was significantly greater than zero in each case and was roughly 2.5%. This suggests that in addition to the BOLD effect there is a baseline signal change which occurs concomitant to neuronal activation in the spinal cord.

A retrospective search for lyssavirus in humans in the Northern Territory.

BACKGROUND: Following the 1996 discovery of a rabies-like lyssavirus in Australian flying foxes, it was unclear whether this was a new epizootic or an unrecognised, previously existing disease. OBJECTIVE: To review cases of unexplained encephalitis in the Northern Territory (NT) to test available clinical specimens for lyssavirus and survey the use of diagnostic tests by clinicians. METHODS: The NT hospital morbidity database was searched from January 1992 to September 1996 for all Royal Darwin Hospital (RDH) cases with an ICD-9 code encompassing encephalitis or viral meningitis. Final diagnoses were determined by hospital record review. For cases of unexplained encephalitis, we assessed the use of diagnostic tests and located clinical specimens for testing for lyssavirus-specific inclusion bodies via immunohistochemistry, immunofluorescence and reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Encephalitis occurred in 34/154 (22%) cases located by the search; 53% (18/34) of encephalitis cases were unexplained. Of these, 24% had no serology performed and 47% had no blood cultures taken. Four (22%) died and two had autopsies. These were the only two cases with clinical specimens available for testing. They were negative for lyssavirus. None of the 71 cases coded as viral meningitis had unexplained encephalitis. CONCLUSION: There was a considerable proportion of unexplained illness among NT cases of encephalitis. IMPLICATIONS: Clinicians should test for lyssavirus in patients with encephalitic symptoms and a postmortem should be sought where death is unexplained. Specimens should be stored to enable testing for emerging infectious diseases.

Universal hepatitis B vaccination: hospital factors influencing first-dose uptake for neonates in Darwin.

A universal neonatal hepatitis B vaccination program was introduced in the Northern Territory in 1990. We compared live births with vaccine usage to determine the uptake of the first dose of hepatitis B vaccine under this new policy and to identify hospital factors that influenced this rate. Attitudes and vaccine administration practices were determined through interviews, using standard questions with midwifery and paediatric nursing staff at both hospitals. Hepatitis B vaccines dispensed at Hospital A indicated a 96 per cent coverage of neonates in 1993 and 93 per cent in 1994. Vaccination at Hospital B indicated 71 per cent coverage in 1993 and 77 per cent in 1994. Differences in vaccine uptake appeared to be influenced by the use of standing drug orders, the nursing staff's attitudes and knowledge, and misinformation among health professionals. Education programs for health professionals and parents need to be established before the introduction of a universal hepatitis B vaccination policy for it to be well accepted. Standing orders for hepatitis B vaccine in postnatal wards allow nursing staff to promote it and thus maximise coverage rates.

Investigation of notifications of hepatitis C in 1994: the experience of three health departments.

Laboratories must notify health departments of cases of hepatitis C in Queensland, the Northern Territory (NT) and the Australian Capital Territory (ACT). Our objectives were to estimate the minimum proportion of notified cases of hepatitis C that were recent infections and to determine the risk factors for infection of the notified cases. We conducted a retrospective investigation of all eligible notifications received at the health departments in Queensland, the Northern Territory and the Australian Capital Territory. Of the 963 notifications about which information was received, 16 per cent were repeat notifications. These were excluded from further analysis. In Queensland, 7 per cent, and in both NT and ACT, 3 per cent of the notifications were considered to be recent infections. The most common risk factor reported for both recent and all other hepatitis C cases was a history of injecting drug use, although the proportion of cases with that history was different in NT from ACT and Queensland. Cases were tested because of screening programs: for drugs and alcohol, in sexually transmitted diseases clinics and prison; and because of clinical indications such as a risk factor, symptoms, or results of liver function tests. Another common reason for testing was a request from a patient. A significant proportion of recorded notifications was repeat notifications. Most notifications were of patients who had become infected more than 12 months ago and the most common risk factor was injecting drug use. There was not a high proportion of cases with unknown risk factors.

Type and mixtures of high-moisture corn in beef cattle finishing diets.

In three experiments consisting of three finishing trials each, five corn storage and(or) feeding treatments were evaluated: 1) dry whole (DWC); 2) whole high-moisture (WHMC); 3) mixture (MHMC) of ground (GHMC) or rolled (RHMC) high-moisture corn with WHMC; 4) GHMC stored in a bunker silo; and 5) RHMC, corn stored whole but fed in rolled form. In Exp. 1, gains and feed intakes of steers fed whole corn (DWC vs WHMC) were similar. Steers fed GHMC and RHMC had lower (P less than .05) gains and intakes than steers fed whole corn. However, feed to gain ratios were 9% better (P less than .10) for steers fed RHMC than for steers fed GHMC. In Exp. 1 and 2, gains of steers fed MHMC were intermediate to gains of steers fed whole (DWC and WHMC) or processed corn (GHMC and RHMC). Feed to gain ratios of steers fed whole or processed corn were similar to feed to gain ratios of steers fed MHMC. In Exp. 3, steers fed 28.6% moisture GHMC had lower (P less than .05) intakes and feed to gain ratios than steers fed 22.5% moisture GHMC. Intakes and feed to gain ratios decreased 1.2 and 1.4%, respectively, for each 1% increase in corn moisture. Data are interpreted to mean that the relative effect of corn moisture content on cattle performance depends on form of corn fed; positive associative effects of MHMC are negligible, but RHMC has a greater feed value than GHMC.