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.^{1 2} There are four DENV serotypes (DENV-1, DENV-2, DENV-3 and DENV-4).³ A fifth DENV type was discovered in samples collected during a dengue outbreak in Sarawak, Malaysia, in 2007; however, its transmission cycle is not believed to be sustained in humans.⁴

Transmission

DENV is transmitted via the bite of infected mosquitoes, predominantly  Aedes aegypti, although Aedes albopictus also has the potential to carry DENV. The virus is maintained in a human- mosquito-human (urban) transmission cycle.^{5 6} There is the chance of non-vector modes of transmission, including through needle-stick injury⁷, transplantation 6.and transfusion of blood components.7 Vertical transmission may also be possible during pregnancy or at birth; infection via such routes does not appear to result in long-term sequelae and there appears to be no association between the severity of disease in the mother and disease in the newborn.^{8 9 10 11} DENV has been detected in the breastmilk of an acutely infected mother, suggesting that this may be a possible additional route of DENV transmission from mother to child.¹²

Epidemiology

According to the World Health Organization (WHO), more than 40 per cent of the world’s population are at risk of dengue fever, with 50–100 million dengue infections occurring worldwide each year. A recent study re-evaluating the global impact of dengue estimated there to be 390 million infections per year (more than three times the WHO estimate).¹³ Although dengue infection is traditionally more common in children, increasing numbers of cases in adults have resulted in more pregnant women being infected.¹⁴ Dengue is endemic in tropical and sub-tropical countries, owing to continual circulation of the virus within an established mosquito population. More than 100 countries are endemic for dengue, including those in Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific. In Australia, dengue is not considered endemic; rather, it is episodic in North Queensland, owing to the presence of the primary vector: Ae. aegypti. Regular outbreaks occur seasonally in North Queensland.^{15 17 18} and, in 2013, this region experienced another outbreak, with approximately 200 confirmed cases.¹⁹ There are a number of factors, such as changes in climate and human behaviour, that suggest that DENV might spread farther in Queensland and indeed to other parts of Australia.^{20 21 22}

Clinical features

Infection can result in dengue fever (DF), dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS), a range of intermediate responses or no clinical response at all.²³ Symptoms may include severe headache, severe joint and muscle pain, retro-orbital pain, nausea and vomiting.²⁴ Life-long immunity to infection occurs, but it is specific for the DENV serotype (cross protection between types persists only for several months). More severe symptoms (DHF, DSS) have been associated with secondary infection with a differing DENV serotype, which can be fatal.²⁵ In pregnant women, dengue infection may result in an acute febrile illness and there is a greater risk of pre-eclampsia, preterm labour and a low birthweight baby.²⁶ Most cases of DF infection in pregnancy result in no serious harm to the mother or baby; however, women who contract DF in early or late pregnancy tend to have a poorer prognosis.14 Severe thrombocytopenia (platelet count of <50 000 cell/mm3) was observed in 79 per cent of a cohort of pregnant women with dengue in India, which included women in the second trimester.²⁷ However, many of these women had an uneventful course of infection, were treated conservatively and discharged.²⁸ Dengue infection in the neonate can range from an asymptomatic or mild disease, to DHF or DSS.²⁹ and passively transferred antibodies, such as in breastmilk from an infected mother, may influence the clinical picture.

Case definition

In Australia, dengue is nationally notifiable, with both confirmed and probable cases requiring notification. A confirmed case requires laboratory definitive evidence (isolation of virus; detection through nucleic acid testing; or detection of DENV NS1 antigen in blood; DENV IgG seroconversion; an increase in DENV antibody level; or the detection of DENV IgM in cerebrospinal fluid, in the absence of IgM to other flaviviruses) and clinical evidence (a clinically compatible illness for example, fever, headache, arthralgia, myalgia, rash, nausea, vomiting and so forth).³⁰ A probable case requires laboratory suggestive evidence (detection of DENV IgM in blood) and clinical evidence as well as epidemiological evidence (a plausible explanation, for instance travel to an area endemic for dengue or exposure in Australia where local transmission has occurred).³¹ Delay in notification is an important factor influencing outbreak duration in Australia15, highlighting the importance of a timely diagnosis and of our notification system.

Treatment and prevention

There are no specific antiviral drugs available for the treatment of dengue infection. Treatment is dependent on symptoms and involves their management. For DF, this usually involves hydration and pain control (paracetamol, codeine or other agents that are not nonsteroidal anti-inflammatory agents). Hospitalisation and additional treatments are often required for DHF or DSS, including IV hydration, blood and/or platelet transfusions, blood pressure support and other intensive-care measures. Studies suggest that during pregnancy most cases require only conservative treatment unless there are complications^{32 33}, and platelet transfusion is only needed for women in labour or with a bleeding disorder.³⁴ There is no vaccine available, despite work in the area for a number of years. There are a number of candidate vaccines in the preclinical or clinical states of evaluation, with additional candidates in the research phase of development.³⁵ Some challenges faced by vaccine developers include the need to protect against all serotypes in naïve as well as previously immune individuals as well as the requirement to induce life-long protection against infection with all serotypes.³⁶ Prevention therefore currently relies on preventing mosquito bites and/or the control of the mosquito vector itself.

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