Epidemiology of dengue in a high-income country: a case study in Queensland, Australia

Background: Australia is one of the few high-income countries where dengue transmission regularly occurs. Dengue is a major health threat in North Queensland (NQ), where the vector Aedes aegypti is present. Whether NQ should be considered as a dengue endemic or epidemic region is an ongoing debate. To help address this issue, we analysed the characteristics of locally-acquired (LA) and imported dengue cases in NQ through time and space. We describe the epidemiology of dengue in NQ from 1995 to 2011, to identify areas to target interventions. We also investigated the timeliness of notification and identified high-risk areas. Methods: Data sets of notified cases and viraemic arrivals from overseas were analysed. We developed a time series based on the LA cases and performed an analysis to capture the relationship between incidence rate and demographic factors. Spatial analysis was used to visualise incidence rates through space and time. Results: Between 1995 and 2011, 93.9% of reported dengue cases were LA, mainly in the 'Cairns and Hinterland' district; 49.7% were males, and the mean age was 38.0 years old. The sources of imported cases (6.1%) were Indonesia (24.6%), Papua New Guinea (23.2%), Thailand (13.4%), East Timor (8.9%) and the Philippines (6.7%), consistent with national data. Travellers importing dengue were predominantly in the age groups 30-34 and 45-49 years old, whereas the age range of patients who acquired dengue locally was larger. The number of LA cases correlated with the number of viraemic importations. Duration of viraemia of public health importance was positively correlated with the delay in notification. Dengue incidence varied over the year and was typically highest in summer and autumn. However, dengue activity has been reported in winter, and a number of outbreaks resulted in transmission year-round. Conclusions: This study emphasizes the importance of delay in notification and consequent duration of viraemia of public health importance for dengue outbreak duration. It also highlights the need for targeted vector control programmes and surveillance of travellers at airports as well as regularly affected local areas. Given the likely increase in dengue transmission with climate change, endemicity in NQ may become a very real possibility

Assessing the threat of chikungunya virus emergence in Australia

Background: Chikungunya virus (CHIKV) is a major threat to Australia given the distribution of competent vectors, and the large number of travellers returning from endemic regions. We describe current knowledge of CHIKV importations into Australia, and quantify reported viraemic cases, with the aim of facilitating the formulation of public health policy and ensuring maintenance of blood safety

Il nome e il sangue secondo Quinto Smirneo. Riprese e trasformazioni di un motivo del duello eroico

The aim of this essay is to examine the rules of duelling in Greek epic poetry from Homer and Arctinus to Quintus Smyrnaeus, within the perspective of composition by theme, which make it possible to identify heroes' ancestry as a specific motif of the epic duel

Antibodies to Leptospira among blood donors in higher-risk areas of Australia: Possible implications for transfusion safety

BACKGROUND: Leptospirosis is one of the most common bacterial zoonoses worldwide, and clinical manifestations range from asymptomatic infection to acute febrile illness, multi-organ failure and death. Asymptomatic, acute bacteraemia in a blood donor provides a potential for transfusion-transmission, although only a single such case from India has been recorded. Human leptospirosis is uncommon in developed countries; however, the state of Queensland in Australia has one of the highest rates among developed countries, especially after increased rainfall. This study examined the prevalence of antibodies to Leptospira spp. in blood donors residing in higher-risk areas of Australia, to evaluate the appropriateness of current blood safety guidelines. MATERIALS AND METHODS: Plasma samples collected from blood donors residing in higher-risk areas of Australia during 2009 and 2011 were included in the study. All samples were tested for the presence of antibodies to 22 leptospiral serovars using the microscopic agglutination test. RESULT: No sample had antibody titres suggestive of a current or recent infection, however, seven samples (1.44%, 95% CI: 0.38-2.50%) had titres suggestive of a past infection. DISCUSSION: This study provides data that may support the appropriateness of current relevant donor selection policies in Australia. Given that the risk profile for leptospirosis is expanding and that the infection is likely to become more prevalent with climate change, this disease may become more of a concern for transfusion safety in the futur

El Niño Southern Oscillation, overseas arrivals and imported chikungunya cases in Australia: A time series analysis.

BACKGROUND: Chikungunya virus (CHIKV) is an emerging mosquito-borne pathogen circulating in tropical and sub-tropical regions. Although autochthonous transmission has not been reported in Australia, there is a potential risk of local CHIKV outbreaks due to the presence of suitable vectors, global trade, frequent international travel and human adaptation to changes in climate. METHODOLOGY/PRINCIPAL FINDINGS: A time series seasonal decomposition method was used to investigate the seasonality and trend of monthly imported CHIKV cases. This pattern was compared with the seasonality and trend of monthly overseas arrivals. A wavelet coherence analysis was applied to examine the transient relationships between monthly imported CHIKV cases and southern oscillation index (SOI) in time-frequency space. We found that the number and geographical distribution of countries of acquisition for CHIKV in travellers to Australia has increased in recent years. The number of monthly imported CHIKV cases displayed an unstable increased trend compared with a stable linear increased trend in monthly overseas arrivals. Both imported CHIKV cases and overseas arrivals showed substantial seasonality, with the strongest seasonal effects in each January, followed by each October and July. The wavelet coherence analysis identified four significant transient relationships between monthly imported CHIKV cases and 6-month lagged moving average SOI, in the years 2009-2010, 2012, 2014 and 2015-2016. CONCLUSION/SIGNIFICANCE: High seasonal peaks of imported CHIKV cases were consistent with the high seasonal peaks of overseas arrivals into Australia. Our analysis also indicates that El Niño Southern Oscillation (ENSO) variation may impact CHIKV epidemics in endemic regions, in turn influencing the pattern of imported cases

Chikungunya virus in Asia - Pacific: a systematic review.

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that causes an acute febrile syndrome and severe, debilitating rheumatic disorders in humans that may persist for months. CHIKV's presence in Asia dates from at least 1954, but its epidemiological profile in the region remains poorly understood. We systematically reviewed CHIKV emergence, epidemiology, clinical features, atypical manifestations and distribution of virus genotypes, in 47 countries from South East Asia (SEA) and the Western Pacific Region (WPR) during the period 1954-2017. Following the Cochrane Collaboration guidelines, Pubmed and Scopus databases, surveillance reports available in the World Health Organisation (WHO) and government websites were systematically reviewed. Of the 3504 records identified, 461 were retained for data extraction. Although CHIKV has been circulating in Asia almost continuously since the 1950s, it has significantly expanded its geographic reach in the region from 2005 onwards. Most reports identified in the review originated from India. Although all ages and both sexes can be affected, younger children and the elderly are more prone to severe and occasionally fatal forms of the disease, with child fatalities recorded since 1963 from India. The most frequent clinical features identified were arthralgia, rash, fever and headache. Both the Asian and East-Central-South African (ECSA) genotypes circulate in SEA and WPR, with ECSA genotype now predominant. Our findings indicate a substantial but poorly documented burden of CHIKV infection in the Asia-Pacific region. An evidence-based consensus on typical clinical features of chikungunya could aid in enhanced diagnosis and improved surveillance of the disease

Plasmalemmal and Secretory Pathway Calcium ATPases in the Mammary Gland

Calcium (Ca2+) is an indispensable intracellular second messenger, essential for cellular life and death. Given the duality of the Ca2+ signal, intracellular Ca2+ levels must be tightly regulated to ensure Ca2+ homeostasis is maintained. Indeed, dysregulation of Ca2+ handling and homeostasis has been associated with a number of different disease states. The cellular arsenal for controlling intracellular Ca2+ includes a multitude of Ca2+ transport proteins, including the plasmalemmal and secretory pathway Ca2+ ATPases (the PMCAs, and SPCAs, respectively). Multiple isoforms of each exist, many of which have different tissue distributions and regulate diverse physiological functions. Secretory pathway Ca2+ ATPase 2 (SPCA2) was first characterised in 2005, and, as such, is the most recently identified Ca2+ ATPase. To date, only a small number of functional studies have been reported on SPCA2, however, a physiological role in secretory cells has been proposed for this novel enzyme. The mammary gland is a unique secretory organ in many ways, but when it comes to Ca2+ regulation and homeostasis it is especially so; during lactation the mammary epithelial cell must transport large quantities of Ca2+ in a unidirectional fashion, concurrent to maintaining a low intracellular Ca2+ concentration. Specific isoforms of plasmalemmal and secretory pathway Ca2+ ATPases are associated with lactation, and indeed with the supply of Ca2+ ions for the enrichment of milk. The recently identified SPCA2 has a number of characteristics suggestive of a role in lactation. This thesis reports the results of an investigation of the hypotheses that SPCAs, in particular the recently identified and less widely expressed SPCA2, are important in mammary gland development, and that different isoforms of plasmalemmal and secretory pathway Ca2+ ATPases have different Plasmalemmal and Secretory Pathway Ca2+ ATPases in the Mammary Gland vii localisations during lactation. The expression of both SPCA1 and SPCA2 in mammary glands isolated from virgin, pregnant, lactating and involuting mice was assessed; a more pronounced increase in SPCA2 mRNA was observed during lactation compared to SPCA1, suggesting that SPCA2 is the predominant SPCA isoform associated with the lactating phenotype. Immunolocalisation studies indicate that different plasmalemmal (PMCA1, PMCA2) and secretory pathway (SPCA1, SPCA2) Ca2+ ATPases have different localisations in the lactating mammary gland in vivo, and in a three-dimensional mammary gland culture model, suggesting different functional roles for these different Ca2+ ATPases during lactation. It is not uncommon for ion transporters, which are up-regulated in lactation to be similarly over-expressed in breast cancer. In addition, there is accumulating evidence to suggest that alterations in cellular Ca2+ signalling and homeostasis are associated with cancer. Indeed certain Ca2+ transport proteins are associated with tumorigenicity and have been identified as possible targets for anti¬cancer therapies. This thesis also reports the results of an investigation of the hypothesis that SPCAs, particularly SPCA2, are important in breast cancer. SPCA1 and SPCA2 mRNA levels were assessed in a bank of breast cancer derived and normal human breast epithelial cell lines and human clinical breast cancer samples. A pronounced increase in SPCA2 mRNA was observed in the breast cancer derived cell lines compared to the normal cell lines, and also in the clinical tumour samples compared to surrounding normal tissue, suggesting that up-regulated SPCA2 is associated with breast cancer. Given that SPCA2 was only identified in 2005, there is a paucity of published studies investigating SPCA2 function. Indeed, there have only been four published reports to date specifically characterising this novel Ca2+ ATPase, coming from only three research laboratories. This thesis reports the results of an investigation, which has attempted to further characterise SPCA2 function viii Plasmalemmal and Secretory Pathway Ca2+ ATPases in the Mammary Gland through gene over-expression and knock-down studies. Collectively, the results presented in this thesis suggest that SPCA2 is not involved in global Ca2+ regulation and proposes that SPCA2 may have a highly specialised role within the cell, which may be associated with Golgi function. In summary, the results presented in this thesis are the first to implicate SPCA2 in a physiological process, and in a disease state, and highlight the importance of this novel enzyme in the mammary gland. They also demonstrate that different isoforms of plasmalemmal and secretory pathway Ca2+ ATPases have different cellular localisations during lactation in the mammary gland, which may suggest different functional roles for these Ca2+ ATPases during this physiological process. In addition, the work presented in this thesis has attempted to characterise the recently identified Ca2+ ATPase, SPCA2, and collectively suggests that SPCA2 is not involved in global Ca2+ regulation, but rather, propose a highly specific physiological role for this novel enzyme within the cell