Introduction
Dengue is an acute febrile disease triggered by an infection with dengue virus (DENV). Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS)[8].
Epidemiology
The disease is now endemic in more than 100 countries in the WHO regions of Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific. The America, South-East Asia and Western Pacific regions are the most seriously affected, with Asia representing approximately 70% of the global burden of disease. In 2020, dengue affected several countries, with increased number of cases in Bangladesh, Brazil, Cook Islands, Ecuador, India, Indonesia, Maldives, Mauritania, Mayotte (Fr), Nepal, Singapore, Sri Lanka, Sudan, Thailand, Timor-Leste and Yemen. In 2021, dengue continues to affect Brazil, Cook Islands, Colombia, Fiji, Kenya, Paraguay, Peru and Reunion Island. _WHO
Microbiology
DENVs are single positive-stranded RNA flaviviruses, members of the Flaviviridae family and there are four distinct, but closely related, serotypes of the virus that cause dengue (DENV-1, DENV-2, DENV-3 and DENV-4). Recovery from infection is believed to provide lifelong immunity against that serotype. However, cross-immunity to the other serotypes after recovery is only partial, and temporary. Subsequent infections (secondary infection) by other serotypes increase the risk of developing severe dengue. _WHO [9]
Mode of transmission
Dengue viruses are spread to people through the bite of an infected Aedes species (Ae. aegypti or Ae. albopictus) mosquito. Incubation period is 4-10 days.
After feeding on a DENV-infected person, the virus replicates in the mosquito midgut, before it disseminates to secondary tissues, including the salivary glands. The time it takes from ingesting the virus to actual transmission to a new host is termed the extrinsic incubation period (EIP). The EIP takes about 8-12 days when the ambient temperature is between 25-28°C [1-3]. Variations in the extrinsic incubation period are not only influenced by ambient temperature; a number of factors such as the magnitude of daily temperature fluctuations[4,5], virus genotype[6], and initial viral concentration[7] can also alter the time it takes for a mosquito to transmit virus. Once infectious, the mosquito is capable of transmitting virus for the rest of its life.
Pathogenesis
Several hypotheses are proposed to explain the reasons for DHF occurrence. These include changes of viral virulence, genetic susceptibility, cytokine storm, variation of lipid profile and immunological enhancement. Although some DHF patients have been reported without previous DENV-exposure, majority of the cases are seen in individuals infected with at least two different serotypes. Hemorrhage in dengue patients can be produced by multiple phenomena such as thrombocytopenia (abnormal low levels of plate-lets), coagulopathy (impaired coagulation), and disruption in the epithelial cells as well as disseminated intravascular coagulation (DIC) [8].
Clinical manifestations
The symptoms usually last for 2-7 days. Dengue fever is suspected in the presence of high grade fever and two other symptoms especially in endemic areas.
- Swollen glands
- High grade fever
- Headache
- Muscle, bone or joint pain
- Nausea and Vomiting
- Retro-orbital Pain
- Rash
Severe dengue fever also known as dengue hemorrhagic fever is a life-threatening emergency and can develop quickly. The warning signs usually begin the first day or two after the fever subsides, and may include:
- Severe abdominal pain
- Persistent vomiting
- Bleeding from gums and orifices
- Hematuria, hematemesis, or hematochezia
- Petechial hemorrhage
- Dyspnea
- Fatigue
- Irritability or restlessness.
Dengue shock syndrome: usually occurs 3-5 days after fever, other clinical features seen include:
- Fever(37.7- 38)
- Hypotension
- Decrease in platelet count leads to leakage of plasma subsequent shock
- Fluid accumulation with respiratory distress
- Critical bleeding
- Organ impairment
- Cardiorespiratory failure and cardiac arrest
Investigations
- Virological methods: the virus may be isolated from blood during the first few days of illness using virological methods such as, reverse transcriptase–polymerase chain reaction (RT–PCR) methods.
- Serological methods: Serological methods, such as enzyme-linked immunosorbent assays (ELISA), may confirm the presence of a recent or past infection, with the detection of IgM and IgG anti-dengue antibodies. IgM antibodies signify a present infection while the presence of IgG antibodies signifies a past infection.
Treatment
There is no specific medicine to treat dengue. Symptomatic treatment is mainly given. Acetaminophen, NSAIDS are given for the fever and myalgia. Patients are rehydrated; fluid input and output are monitored diligently. Adequate nutrition of the patient is ensured.
Prevention
Primary prevention: involves creating awareness on dengue fever and its mode of transmission, vector control and vaccination. Control of transmission of dengue virus can be achieved by preventing mosquitoes from accessing egg-laying habitats by environmental management and modification, indoor residual spraying, wearing protective clothing, use of mosquito repellant creams amongst other methods. The first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur was licensed in December 2015 and has now been approved by regulatory authorities in approximately 20 countries.
Secondary prevention: this involves early diagnosis and adequate treatment of dengue fever cases.
Tertiary prevention: complications of dengue fever are prevented and managed if they occur.
References
[1] Tjaden, N.B., et al., Extrinsic Incubation Period of Dengue: Knowledge, Backlog, and Applications of Temperature Dependence. Plos Neglected Tropical Diseases, 2013. 7(6): p. 5.
[2] Siler, J.F., M.W. Hall, and A.P. Hitchens, Dengue: Its history, epidemiology, mechanism of transmission, etiology, clinical manifestations, immunity and prevention. 1926, Manila: Bureau of Science.
[3] Watts, D.M., et al., Effect of Temperature on the vector efficiency of Aedes aegypti for Dengue 2 virus. American Journal of Tropical Medicine and Hygiene, 1987. 36(1): p. 143-152.
[4] Carrington, L.B., et al., Fluctuations at low mean temperatures accelerate dengue virus transmission by Aedes aegypti. PLOS Neglected Tropical Diseases, 2013. 7(4): p. e2190.
[5] Lambrechts, L., et al., Impact of daily temperature fluctuations on dengue virus transmission by Aedes aegypti. Proceedings of the National Academy of Sciences of the United States of America, 2011. 108(18): p. 7460-7465.
[6] Anderson, J.R. and R. Rico-Hesse, Aedes aegypti vectorial capacity is determined by the infecting genotype of dengue virus. American Journal of Tropical Medicine and Hygiene, 2006. 75(5): p. 886-892.
[7] Ye, Y.X.H., et al., Wolbachia Reduces the Transmission Potential of Dengue-Infected Aedes aegypti. PLOS Neglected Tropical Diseases, 2015. 9(6): p. e0003894.
[8] Wang WH, Urbina AN, Chang MR, Assavalapsakul W, Lu PL, Chen YH, Wang SF. Dengue hemorrhagic fever - A systemic literature review of current perspectives on pathogenesis, prevention and control. J Microbiol Immunol Infect. 2020 Dec;53(6):963-978. doi: 10.1016/j.jmii.2020.03.007. Epub 2020 Mar 26. PMID: 32265181
[9] WHO NEWSROOM- www.who.int/newsroom