Influenza as a trigger for cardiovascular disease: An investigation of serotype, subtype and geographic location.

BACKGROUND: Seasonal peaks of influenza and cardiovascular disease tend to coincide. Many excess deaths may be triggered by influenza, and the severity of this effect may vary with the virulence of the circulating influenza strain and host susceptibility. We aimed to explore the association between hospital admissions for influenza and/or pneumonia (IP) and acute myocardial infarction (AMI) or ischaemic heart disease (IHD) in Queensland, Australia, taking into account temporal and spatial variation of influenza virus type and subtype in 2007, 2008 and 2009. METHODS: This ecological study at Statistical Subdivision level (SSD, n=38) used linked patient-level data. For each study year, Standardized Morbidity Ratios (SMRs) were calculated for hospital admissions with diagnoses of IP, AMI and IHD. We investigated the associations between IP and AMI or IHD using spatial autoregressive modelling, adjusting for socio-demographic factors. RESULTS: Spatial autocorrelation was detected in SMRs, possibly reflecting underlying social and behavioural risk factors, but consistent with infectious disease spread. SMRs for IP were consistently predictive of SMRs for AMI and IHD when adjusted for socioeconomic status, population density and per cent Indigenous population (coefficient: 0.707, 95% confidence interval (CI): 0.318 - 1.096; 0.553, 0.222 - 0.884; 0.598, 0.307 - 0.888 and 1.017, 0.711 - 1.323; 0.650, 0.342 - 0.958; 1.031, 0.827 - 1.236) in 2007, 2008 and 2009, respectively. CONCLUSIONS: This ecological study provides further evidence that severe respiratory infections may trigger the onset of cardiovascular events, implicating the influenza virus as a contributing factor.

General resource for ionospheric transient investigations (GRITI): An open-source code developed in support of the Dinsmore et al. (2021) results.

The analysis techniques and the corresponding software suite GRITI (General Resource for Ionospheric Transient Investigations) are described. GRITI was used to develop the Dinsmore et al. [2] results, which found a novel classification of traveling ionospheric disturbances (TIDs) called semi-coherent ionospheric pulsing structures (SCIPS). The any-geographic range (local-to-global), any-azimuth angle keogram algorithm used to analyze SCIPS in that work is detailed. The keogram algorithm in GRITI is applied to detrended vTEC (vertical Total Electron Content) data, called delta-vTEC herein, in Dinsmore et al. [2] and the follow-on paper Dinsmore et al. [3], but is also applicable to any other two-dimensional dataset that evolves through time. GRITI's delta-vTEC processing algorithm is also described in detail, which is used to provide the delta-vTEC data for Dinsmore et al. [3]. •We detail a keogram algorithm for analysis of delta-vTEC data in Dinsmore et al. [2] and the follow-on paper Dinsmore et al. [3].•We detail a delta-vTEC processing algorithm that converts vTEC data to delta-vTEC through detrending that is used to provide the delta-vTEC data used in Dinsmore et al. [3].•GRITI is an open-source Python 3 analysis codebase that encompasses the delta-vTEC processing and keogram algorithms. GRITI has additional support for other data sources and is designed for flexibility in adding new data sources and analysis methods. GRITI is available for download at: https://github.com/dinsmoro/GRITI.

Outbreak of Notozothecium bethae (Monogenea: Dactylogyridae) in Myleus schomburgkii (Actinopterygii: Characiformes) cultured in the Peruvian Amazon.

The presence of Notozothecium bethae was investigated in 76 black band myleus (Myleus schomburgkii [Actinopterygii: Charasiformes]) born and kept in captivity in two semi-intensive breeding cages in the northern region of Peru. Among the 76 cultivated specimens of M. schomburgkii examined in the present study, 100 % had monogenean on the gill and the parasites were identified as Notozothecium bethae. During the survey no bacteria was isolated, and no protozoan or other metazoan parasites were found. The prevalence of N. bethae remained constant throughout the present study. Mean intensity of N. bethae in the months of April and May was exceptionally high in both facilities. The massive infection of N. bethae on the gills of M. schomburgkii was associated with mortality. This is the first report of N. bethae in M. schomburgkii born in captivity and cultured in the Amazon region. The mortality due the presence of this parasite emphasise the need for disease control strategies of cultured M. schomburgkii.

Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.

Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants.

Otitis media (OM) develops in the first months of life and persists throughout childhood in many rural Aboriginal children. We have followed Aboriginal and non-Aboriginal infants from birth to determine the relationship of the early onset of OM to nasopharyngeal colonization with respiratory pathogens. Aboriginal infants were colonized with multiple species of respiratory bacteria (Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae) at a rate of 5% per day and the timing of colonization predicted the onset of persistent OM in individual Aboriginal infants. Non-Aboriginal infants became colonized by M. catarrhalis alone at the slower rate of 1% per day and experienced transient episodes of OM in the absence of colonization. We attribute early bacterial colonization in most Aboriginal infants to high rates of cross-infection due to overcrowding, poor hygiene and high rates of bacterial carriage. Early age of infection and the multiplicity of bacterial types may contribute to prolonged carriage and to eustachian tube damage leading to persistent OM. Thus Aboriginal infants are "otitis-prone" and might qualify for prophylactic antibiotics.

Genetically distinct dog-derived and human-derived Sarcoptes scabiei in scabies-endemic communities in northern Australia.

Overcrowding is a significant factor contributing to endemic infection with Sarcoptes scabiei in human and animal populations. However, since scabies mites from different host species are indistinguishable morphologically, it is unclear whether people can be infected from scabies-infested animals. Molecular fingerprinting was done using three S. scabiei-specific single locus hypervariable microsatellite markers, with a combined total of 70 known alleles. Multilocus analysis of 712 scabies mites from human and dog hosts in Ohio, Panama and Aboriginal communities in northern Australia now shows that genotypes of dog-derived and human-derived scabies cluster by host species rather than by geographic location. Because of the apparent genetic separation between human scabies and dog scabies, control programs for human scabies in endemic areas do not require resources directed against zoonotic infection from dogs.

Modelling of endemic carriage of Haemophilus influenzae in Aboriginal infants in Northern Australia.

Aboriginal infants and children in rural communities in Northern Australia have high rates of nasopharyngeal carriage of nonencapsulated Haemophilus influenzae (NCHi), with positive swab rates of 76%. In this population, the acquisition of NCHi from soon after birth is associated with the onset of otitis media and with muco-purulent nasal discharge, while the long-term persistence of NCHi carriage is associated with the acquisition and turnover of large numbers of antigenically diverse strains. Mathematical models have been fitted to data on the acquisition and loss of encapsulated strains of H. influenzae and 43 different strains of NCHi in 10 children followed from early infancy for up to 2 years. Subject to plausible assumptions, the preferred model estimated the mean time to acquisition of a H. influenzae strain to be 7 days after first becoming exposed after birth. For an infant already carrying H. influenzae, each additional strain was acquired after a mean waiting period of 45 days. On average, 1.50 different strains of H. influenzae were detected in four colonies routinely typed from each positive swab, but it was estimated that another 2.55 strains were 'hidden' behind these more frequent strains. With an average of 4.05 strains per carrier, it was estimated that each strain was carried for an average of 137 days, although detected on only 37% of occasions. Thus we have developed mathematical models that provide estimates for duration of colonisation, time to colonisation, and number of colonising strains in a population in which H. influenzae is highly endemic, characterised by sequential and concurrent carriage of multiple strains in each infant.

Diabetic surveys in Papua New Guinea - results and implications.

Glucose intolerance was found in 22% of the residents of Koki in Port Moresby, 5% of residents in the coastal village of Kalo and in 3% of 120 young civil servants. The respective prevalences of frank diabetes mellitus were 15.6%, 1% and 0%. Cholesterol and triglyceride levels were similar and low in all groups, despite both obesity and glucose intolerance in the urban-Koki residents who also had a significantly higher blood pressure. There is a need to identify those areas of Papua New Guinea where, in a similar fashion to other countries in the South Pacific, diabetes mellitus is increasing. Simple measures of dietary restriction and increased exercise may be effective in preventing diabetes from becoming a major health problem particularly in identified high prevalence areas.

The influence of changing host immunity on 1918-19 pandemic dynamics.

The sociological and biological factors which gave rise to the three pandemic waves of Spanish influenza in England during 1918-19 are still poorly understood. Symptom reporting data available for a limited set of locations in England indicates that reinfection in multiple waves occurred, suggesting a role for loss of infection-acquired immunity. Here we explore the role that changes in host immunity, driven by a combination of within-host factors and viral evolution, may play in explaining weekly mortality data and wave-by-wave symptomatic attack-rates available for a subset of English cities. Our results indicate that changes in the phenotype of the pandemic virus are likely required to explain the closely spaced waves of infection, but distinguishing between the detailed contributions of viral evolution and changing adaptive immune responses to transmission rates is difficult given the dearth of sero-epidemiological and virological data available even for more contemporary pandemics. We find that a dynamical model in which pre-pandemic protection in older "influenza-experienced" cohorts is lost rapidly prior to the second wave provides the best fit to the mortality and symptom reporting data. Best fitting parameter estimates for such a model indicate that post-infection protection lasted of order months, while other statistical analyses indicate that population-age was inversely correlated with overall mortality during the herald wave. Our results suggest that severe secondary waves of pandemic influenza may be triggered by viral escape from pre-pandemic immunity, and thus that understanding the role of heterosubtypic or cross-protective immune responses to pandemic influenza may be key to controlling the severity of future influenza pandemics.

Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning.

The panzootic of H5N1 influenza in birds has raised concerns that the virus will mutate to spread more readily in people, leading to a human pandemic. Mathematical models have been used to interpret past pandemics and outbreaks, and to thus model possible future pandemic scenarios and interventions. We review historical influenza outbreak and transmission data, and discuss the way in which modellers have used such sources to inform model structure and assumptions. We suggest that urban attack rates in the 1918-1919 pandemic were constrained by prior immunity, that R(0) for influenza is higher than often assumed, and that control of any future pandemic could be difficult in the absence of significant prior immunity. In future, modelling assumptions, parameter estimates and conclusions should be tested against as many relevant data sets as possible. To this end, we encourage researchers to access FluWeb, an on-line influenza database of historical pandemics and outbreaks.

NHMRC workshop on non-pharmacological methods of lowering blood pressure. Is alcohol use a preventable cause of hypertension?

There is good evidence that hypertension is more frequently observed in alcohol-users than in non-users, and that the prevalence of hypertension is proportional to the average dose of alcohol consumed. If this association is causal, the 20% to 50% of hypertension in middle-aged Australian men which is attributable to alcohol use could prove to be entirely preventable. On the other hand, if the association is largely secondary, that is, if alcohol use and hypertension share genetic and other causes in common, then intervention to reduce alcohol consumption could have little effect on the prevalence of hypertension. Further work is needed to study the mechanisms by which alcohol use may cause hypertension, to identify the genetic factors which may determine susceptibility to hypertension in alcohol-users, and to carry out controlled intervention studies to test the hypothesis that alcohol use is a reversible cause of hypertension.

The Menzies School of Health Research offers a new paradigm of cooperative research.

The Menzies School has addressed problems in Aboriginal and tropical health through research that requires cooperation between disciplines as well as improved communication and trust between researchers, Aboriginal people and the wider community.

Alcohol use, hypertension and coronary heart disease.

1. Male death rates from hypertension and stroke in England and Wales in 1949-53 were highest in those socio-economic and occupational groups with the highest death rates for cirrhosis of the liver (and presumably with highest alcohol intake. 2. In prevalence data from the Busselton population in Western Australia in 1969, there was a significant association between hypertension and a history of heavy drinking. 3. Together with other data, these observations suggest that up to 30% of hypertension in affluent countries may prove to be attributable to the use of alcohol.

Alcohol usage as a possible explanation for socio-economic and occupational differentials in mortality from hypertension and coronary heart disease in England and Wales.

Alcohol usage as a possible explanation for socio-economic and occupational differentials in mortality from hypertension and coronary heart disease in England and Wales.

Ischaemic heart-disease: possible genetic markers.

National death-rates from ischaemic heart-disease are significantly correlated with population frequencies of histocompatibility antigen HLA-8 and haplotype 1-8. Serum-cholesterol levels may also be correlated with population frequencies of HLA-8. Inexplicably high death-rates from ischaemic heart-disease and high levels of serum-cholesterol in Finland may be due to the combined effects of HLA-8 and W15. It is suggested that HLA-8 (and possibly W15) are linked to genes which predispose to hypercholesterolaemia and ischaemic heart-disease. These findings provide some support for i-munogenetic hypotheses for vascular disease in man.