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

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

Packed red blood cell transfusion modulates myeloid dendritic cell activation and inflammatory response in vitro

Transfusion of packed red blood cells (PRBCs) modulates patients' immune responses and clinical outcomes; however, the underpinning mechanism(s) remain unknown. The potential for PRBC to modulate myeloid dendritic cells (mDC) and blood DC antigen 3 was assessed using an in vitro transfusion model. In parallel, to model processes activated by viral or bacterial infection, toll-like receptor agonists polyinosinic:polycytidylic acid or lipopolysaccharide were added. Exposure to PRBC upregulated expression of CD83 and downregulated CD40 and CD80 on both DC subsets, and it suppressed production of interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-gamma-inducible protein-10 by these cells. Similar effects were observed when modeling processes activated by concurrent infection. Furthermore, exposure to PRBC at date of expiry was associated with more pronounced effects in all assays. Our study suggests PRBC have an impact on recipient DC function, which may result in failure to establish an appropriate immune response, particularly in patients with underlying infection

Platelet concentrates modulate myeloid dendritic cell immune responses

Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3 DC were assessed following exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry). In parallel, to model recipients with underlying viral or bacterial infection, polyinosinic:polycytidylic acid or lipopolysaccharide was added. Exposure to PC had less of an impact on mDC responses than BDCA3 DC responses. PC alone downregulated BDCA3 DC expression of co-stimulatory molecules CD40 and CD80. In the model of viral infection, PC downregulated expression of CD83, and in the bacterial model of infection, PC downregulated CD80, CD83, and CD86. PC alone suppressed mDC production of interleukin (IL)-8, IL-12 and tumor necrosis factor (TNF)-α and BDCA3 DC production of IL-8, IL-12, and IL-6. In the model of viral infection, production of IL-12 and interferon-gamma inducible protein (IP)-10 was reduced in both DC subsets, and IL-8 was reduced in BDCA3 DC following PC exposure. When modeling bacterial infection, PC suppressed mDC and BDCA3 DC production of IL-6 and IL-10 with a reduction in TNF-α evident in mDC. This study assessed the impact of PC "transfusion" on DC surface antigen expression and inflammatory mediator production and provided the first evidence that PC transfusion modulates blood mDC and BDCA3 DC maturation and activation, particularly in the models of infection. Results of this study suggest that patients who receive PC, particularly those with underlying infectious complications, may fail to establish an appropriate immune response precipitating poor patient outcomes

Dengue in Australia: the key points

Dengue is responsible for upwards of 50 million infections per year worldwide; however, given that asymptomatic infection is possible, the true incidence is thought to be far higher. The virus is emerging or re-emerging in many regions of the world, including Australia, where episodic outbreaks occur in North Queensland. With a changing future climate, household water storage and mosquito distribution could affect outbreak frequency and the geographic distribution of this virus. Virology Dengue viruses (DENV) are enveloped viruses in the family Flaviviridae; genus Flavivirus. The genome is positive-sense, single-stranded RNA, which encodes seven non-structural proteins (including NS1, which is used for laboratory testing – see below) and three structural proteins

Incorporation of fluorescein conjugated function-spacer-lipid constructs into the red blood cell membrane facilitates detection of labeled cells for the duration of ex-vivo storage

The contribution of ex-vivo storage duration of packed red blood cells (PRBC) to patient outcomes and transfusion-related immunomodulation (TRIM) remains a broadly debated area in transfusion medicine. Kode™ Technology with fluorescein conjugated function-spacer-lipid (FSL-FLRO4) constructs is a tool that can aid in-vitro visualization and tracking of red blood cells (RBC) during routine storage. FSL-FLRO4 is incorporated into the RBC membrane without altering cell function. In this study, we explore the suitability of this technology to label clinical grade PRBC and to determine if the label would be retained during ex-vivo storage. Firstly, to confirm feasibility and assess the limit of detection of FSL-FLRO4 on PRBC at date of expiry (42 days post-collection), we tracked the binding of FSL-FLRO4 on PRBC at weekly intervals during routine storage. Over the time course, all cells remained labelled with FSL-FLRO4, although a decrease in the intensity of labelling was observed (P < 0.0001). We then further investigated differences in FSL-FLRO4 labelling during RBC storage by labelling separated light-young and dense-old RBC from the same PRBC unit. There were no differences in the capacity of FSL-FLRO4 to label these different RBC subsets. Together, these data demonstrate that FSL-FLRO4 is a suitable reagent for labelling PRBC at any point during routine storage. This technology will facilitate the development of immunoassays and transfusion models focused on addressing the mechanisms involved in TRIM

The impact on blood donor screening for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus using plasma from frozen-thawed plasma preparation tubes

BACKGROUND Blood services are required to maintain repositories of frozen samples for confirmation of results and/or retrospective testing. The Australian Red Cross Blood Service archives donor samples in plasma preparation tubes (PPTs). This study aims to evaluate the effect of freeze-thawing and extended frozen storage on the ability to detect human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) using blood donation screening assays in samples stored in PPTs. STUDY DESIGN AND METHODS Whole blood was spiked with HIV-, HCV-, or HBV-reactive plasma at high and low viral loads and stored in PPTs or as plasma aliquots. All samples were frozen and stored at not more than -30°C. At 0, 3, 6, 12, 18, and 36 months, samples were tested for HIV and HCV antibodies, HBV surface antigen, and viral nucleic acid. Additional samples were thawed and refrozen either once or twice before testing to simulate up to three freeze-thaw cycles. RESULTS All PPT and plasma aliquots retained appropriate viral reactivity, including those with multiple freeze-thaw cycles, on both nucleic acid testing and serology platforms. CONCLUSION Frozen storage of biologicals in PPTs, as opposed to plasma aliquots, does not affect the ability to detect HIV, HCV, and HBV using viral nucleic acid or serology donation screening systems for up to 36 months. Freezing and thawing PPT samples did not impact the ability to detect these viruses. Our study demonstrates that PPTs appear to be an appropriate receptacle for frozen plasma sample archiving for up to 3 years

Plasma selenium status in a group of Australian blood donors and fresh blood components

The purpose of this study was to assess plasma selenium levels in an Australian blood donor population and measure extra-cellular selenium levels in fresh manufactured blood components. Selenium levels were measured using graphite furnace atomic absorption spectrometry with Zeeman background correction. The mean plasma selenium level in healthy plasmapharesis donors was 85.6. ±. 0.5. μg/L and a regional difference was observed between donors in South East Queensland and Far North Queensland. Although participants had selenium levels within the normal range (55.3-110.5. μg/L), 88.5% had levels below 100. μg/L, a level that has been associated with sub-optimal activity of the antioxidant enzyme glutathione peroxidase (GPx). Extra-cellular selenium levels in clinical fresh frozen plasma (cFFP) and apheresis-derived platelets (APH Plt) were within the normal range. Packed red blood cells (PRBC) and pooled buffy coat-derived platelets (BC Plt) had levels at the lower limit of detection, which may have clinical implications to the massively transfused patient