VIROLOGY
fever and Japanese encephalitis.10 Furthermore, the IgG ELISA in a single serum sample is of little use as it will be detectable for life following dengue virus infection.8
Recently the mainstay for laboratory diagnostics has been polymerase chain reaction (PCR) methods. These detect viral RNA highly specific to the dengue virus including differentiation of the four serotypes. In days 1–7 of the acute phase the RNA is easily detected. PCR methods can be either monoplex specific for individual serotypes, or as a multiplex screen that includes differentiation of the four dengue serotypes. Furthermore, the dengue virus can be detected as part of a syndromic multiplex assay to look at a range of viruses showing similar symptoms and epidemiology. These syndromic screens include multiplex dengue, Zika and chikungunya virus assays. Both dengue and Zika diagnostics are listed as essential within the WHO Model List of Essential In Vitro Diagnostics,12
and chikungunya virus has Fig 3. Certest Biotec Viasure Tropical Panel 1.13
the majority of primary infections being classified as mild, they are often undifferentiated from other viral diseases. As it is clinically difficult to differentiate between these viruses, it is considered to be significantly underdiagnosed and under-reported.11 Severe dengue following the acute febrile stage indicated by mild disease is characterised by severe plasma leakage leading to shock and fluid accumulation, respiratory distress, severe bleeding and organ impairment. It can go on to cause a haemorrhagic fever, commonly termed dengue haemorrhagic fever (DHF), which can lead to thrombocytopenia, serious bleeding and may result in dengue shock syndrome.10
This can cause severe shock
The dengue virus can cause disease in anyone, but under five-year-
due to sudden drop in blood pressure, a reduction of circulating platelets causing blood vessel leakage, and may ultimately cause death. Death from severe dengue occurs in 2.5% of cases and for those who have a significant drop in blood pressure this can prove fatal in up to 26% of cases.10
olds and the elderly are at a higher risk of a poor prognosis.2
In non-endemic
countries a lack of awareness and diagnostic capability probably leads to significant under-reporting. For severe cases with the possibility of severe shock, haemorrhage and DHF, the importance of recent travel along with the clinical symptoms must not be underestimated.
Diagnosis
As indicated, diagnosis is often difficult without clinical suspicion and travel knowledge, as dengue is very similar to other tropical diseases prevalent in endemic areas. Moreover, a lack of knowledge in both endemic and non-endemic areas as indicated in the WHO Neglected Pathogens List,9
makes diagnosing this disease particularly difficult. While there are both IgM and IgG serological enzyme- linked immunosorbent assay (ELISA) tests available, interpretation of results is complicated by significant cross- reactivity with other flaviviruses, and vaccines to them; namely, Zika, yellow
symptoms very similar to dengue and Zika infections.
Testing
Certest Biotec manufactures the Viasure molecular assays, and its tropical diseases assays are particularly relevant, as they cover several viruses and contain freeze-dried reagents that have a 24-month shelf-life.13
This lends their
assays to be used in remote locations without the need for cold-chain supply and storage. This is particularly relevant to Africa where it is suggested that significant underreporting is evident. The assay range covers a plethora of microbial targets, and the company’s tropical and vector-borne range includes single monoplex RT-PCR assays for all the viruses above, a dengue type- specific multiplex covering DENV1–4, and a multiplex covering chikungunya, dengue and Zika viruses within the same tube.13
Treatment and vaccines Vaccine development against the dengue virus has been around for a long time, and began in the 1920s. However, creating a vaccine that provides immunity to all four strains has been troublesome.2
Vaccine
Dengue is an acute viral illness and diseases caused vary in their severity, with up to 80% of dengue virus infections being asymptomatic or only producing a mild self-limiting illness
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development has been further hindered by a phenomenon known as antibody- dependant enhancement with one of the vaccines. This phenomenon can promote dengue virus infection by enhancing viral phagocytosis into the host cell and increase the risk of severe dengue in those who have not previously been infected.14
This vaccine is JUNE 2024
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