Dengue Disease

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University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[1]

Etiology/Bacteriology

Taxonomy

Group = Group IV positive-sense ssRNA virus | Order = Unassigned | Family = Flaviviridae | Genus = Flavivirus | species = Dengue Virus

NCBI Taxonomy: (DENV-1) (DENV-2) (DENV-3) (DENV-4) Genome: Dengue Virus

Description

Dengue (pronounced DENgee) viruses belong to the family Flaviviridae, genus Flavivirus. There are four serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, which belong to a larger, heterogeneous group of viruses called arboviruses. This is an ecological classification, one which implies that transmission between vertebrate hosts, humans, is dependent on hematophagous arthropod vectors. Dengue fever is transmitted by the bite of an Aedes mosquito infected with a dengue virus. The mosquito becomes infected when it bites a person with dengue virus in their blood. It can’t be spread directly from one person to another person. Dengue fever is a painful, debilitating mosquito-borne disease. This disease has symptoms similar to the flu, however the symptoms may progress to massive bleeding, shock, and death. This is called dengue shock syndrome (DSS).This virus is related to the viruses that cause West Nile infection and yellow fever. Each year, an estimated 100 million cases of dengue fever occur worldwide, with most of these cases occurring in tropical areas of the world. [1]

The Dengue Virus is considered an Old Disease, which goes back to the Chin Dynasty (AD 265–420), where it was first recorded. There are reports of epidemics of dengue-like illnesses in the French West Indies in 1635 and in Panama in 1699. By the late 1700s, the disease had a worldwide distribution in the tropics: Indonesia, Egypt, and in 1780 in Philadelphia. [6] From the late 1700s to World War II, repeated epidemics of dengue illness occurred in most tropical and subtropical regions of the world.

Pathogenesis

Transmission

Dengue virus infections come from the bite of an infected Aedes mosquito. These mosquitoes usually live between the latitudes of 35 degrees North and 35 degrees South below an elevation of 1,000 metres (3,300 ft).[5] Mosquitoes become infected when they bite infected humans, and later transmit infection to other people they bite. The two main species of mosquito, Aedes aegypti and Aedes albopictus, have been responsible for 95% of cases of dengue transmitted, however other mosquito species such as A. albopictus, A polynesiensis and several A. scutellaris may also transmit the disease.[6] Humans are the primary host of the virus, but it may also circulate in nonhuman primates.[3] An infection may be acquired via a single bite.[4] After taking a blood meal from an infected person, the virus infects the cells lining the mosquito's gut. About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus has no effect on the mosquito, which remains infected for life. Dengue may also be transmitted via infected blood products and through organ donation. [5]

Epidemiology

With the proper healthcare, patients with the Dengue diagnosis recover. The mortality rate is 1–5% without treatment. Severe disease carries a mortality of 26%.[3] Dengue is believed to infect 50 to 100 million people a year worldwide, with hundreds of thousands of life-threatening infections requiring hospitalization resulting in approximately 12,500-25,000 deaths.[7]

The burden of disease from dengue is estimated to be similar to other childhood and tropical diseases, such as tuberculosis, at 1600 disability-adjusted life years per million population. It is the most common viral disease transmitted by arthropods.[3] As a tropical disease it is deemed only second in importance to malaria. While once exclusively a tropical disease it has become global, and is endemic in more than 110 countries. The World Health Organization counts dengue as one of sixteen neglected tropical diseases.[7]

The incidence of dengue increased 30 fold between 1960 and 2010. This increase is believed to be due to a combination of urbanization, population growth, increased international travel, and global warming. The geographical distribution is around the equator with 70% of the total 2.5 billion people living in endemic areas from Asia and the Pacific. In the United States, the rate of dengue infection among those who return from an endemic area with a fever is 2.9–8.0%,[7] and it is the second most common infection after malaria to be diagnosed in this group.[7]

Virulence factors

Dengue

Like all Gram negative bacteria, EHEC outer membranes have an outer facing leaflet of lipopolysaccharide (LPS). LPS consists of lipid A, core polysaccharide, and O-Antigen, which consists of 40-80 repeating subunits of 4 sugars that in the case of E. coli O157:H7 is unique to the O157 serogroup, containing N-acetyl-d-perosamine, l-fucose, d-glucose, and N-acetyl-d-galactose. The core polysaccharide essentially is conserved in all E. coli ecotypes. Lipid A is the toxic component of LPS, also known as endotoxin, which is a heat-stable toxin. Lipid A consists of a phosphorylated disaccharide of glucosamine linked by a beta-1,6 linkage and modified by fatty acids, in addition to the first ketodeoxyoctanoate of the core polysaccharide. Endotoxin is released by cell lysis rather than being secreted. Endotoxin is less potent and less specific than exotoxins. Endotoxin can cause fever, hemorrhagic shock, and diarrhea.

Prevention

Prevention depends on control of and protection from the bites of the mosquito that transmits it. The World Health Organization recommends a Integrated Vector Control program consisting of five elements: (1) Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened, (2) collaboration between the health and other sectors (public and private), (3) an integrated approach to disease control to maximize use of resources, (4) evidence-based decision making to ensure any interventions are targeted appropriately and (5) capacity-building to ensure an adequate response to the local situation.[9]

The primary method of controlling A. aegypti is by eliminating its habitats.[9] This may be done by emptying containers of water or by adding insecticides or biological control agents to these areas. Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effect from insecticides and greater logistical difficulties with control agents. People may prevent mosquito bites by wearing clothing that fully covers the skin and/or the application of insect repellent (DEET being the most effective).[9] A number of novel methods have been used to reduce mosquito numbers with some success including the placement of the fish Poecilia reticulata or copepods in standing water to eat the mosquito larva.

There are currently no approved vaccines for the dengue virus. There are ongoing programs working on a dengue vaccine to cover all four serotypes. One of the concerns is that a vaccine may increase the risk of severe disease through antibody-dependent enhancement. A number of vaccines are currently undergoing testing.[8]

Host Immune Response

The virus has an incubation period of 4-10 days after the bite from an infected mosquito. Symptoms usually last for 2-7 days post incubation. The next 24-48 hours of the critical stage can be lethal; proper medical care is needed to avoid complications and risk of death. The warning signs to look out for occur 3-7 days after the first symptoms. [2]

Damage Response Timeline [2]

References

Created by Brandon Kitchens, students of Tyrrell Conway at the University of Oklahoma.

1 Karriem-Norwood, Varnada, MD. "Dengue Fever: Symptoms, Causes, and Treatments." WebMD. WebMD, 20 Sept. 2012. Web. 24 July 2015

2Martina, B. E. E., Koraka, P., & Osterhaus, A. D. M. E. Dengue virus pathogenesis: An integrated view. Clinical Microbiology Reviews 22, 564–581 (2009). doi:10.1128/CMR.00035-09

3"Vector-Borne Viral Infections". World Health Organization. Retrieved 17 January 2011.

4 Retrieved 2010-12-23Center for Disease Control and Prevention. "Chapter 5 – Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF)". 2010 Yellow Book.

5 Wilder-Smith A, Chen LH, Massad E, Wilson ME (January 2009). "Threat of dengue to blood safety in dengue-endemic countries". Emerging Infect. Dis. 15 (1): 8–11. doi:10.3201/eid1501.071097. PMID 19116042. PMC 2660677.

6 S. B. Halstead (2007) Dengue. Lancet 370, 1644-1652

7 CDC. "Epidemiology." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 09 June 2014. Web. 24 July 2015.

8 Vaccine Development, Dengue Vaccine Initiative, November 2012, accessed November 5, 2013

9 WHO media centre (March 2009). "Dengue and dengue haemorrhagic fever". World Health Organization.. Retrieved 2010-12-27.