Dengue Fever

 

Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. This may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Recovery generally takes two to seven days. In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.

Dengue is spread by several species of mosquito of the Aedes type, principally A. aegypti. The virus has five different types; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. A number of tests are available to confirm the diagnosis including detecting antibodies to the virus or its RNA.

A vaccine for dengue fever has been approved and is commercially available in a number of countries. Other methods of prevention are by reducing mosquito habitat and limiting exposure to bites. This may be done by getting rid of or covering standing water and wearing clothing that covers much of the body. Treatment of acute dengue is supportive and includes giving fluid either by mouth or intravenously for mild or moderate disease. For more severe cases blood transfusion may be required. About half a million people require admission to hospital a year. Paracetamol (acetaminophen) is recommended instead of nonsteroidal anti-inflammatory drugs (NSAIDs) for fever reduction and pain relief in dengue due to an increased risk of bleeding from NSAID use.

Dengue has become a global problem since the Second World War and is common in more than 110 countries. Each year between 50 and 528 million people are infected and approximately 10,000 to 20,000 die. The earliest descriptions of an outbreak date from 1779. Its viral cause and spread were understood by the early 20th century. Apart from eliminating the mosquitoes, work is ongoing for medication targeted directly at the virus. It is classified as a neglected tropical disease.

Prevention
Prevention depends on control of and protection from the bites of the mosquito that transmits it. The World Health Organization recommends an Integrated Vector Control program consisting of five elements:

Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened;
Collaboration between the health and other sectors (public and private);
An integrated approach to disease control to maximize use of resources;
Evidence-based decision making to ensure any interventions are targeted appropriately; and
Capacity-building to ensure an adequate response to the local situation.
The primary method of controlling A. aegypti is by eliminating its habitats. This is done by getting rid of open sources of water, or if this is not possible, by adding insecticides or biological control agents to these areas. Generalized spraying with organophosphate or pyrethroid insecticides, while sometimes done, is not thought to be effective. Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effects from insecticides and greater logistical difficulties with control agents. People can prevent mosquito bites by wearing clothing that fully covers the skin, using mosquito netting while resting, and/or the application of insect repellent (DEET being the most effective). However, these methods appear not to be sufficiently effective, as the frequency of outbreaks appears to be increasing in some areas, probably due to urbanization increasing the habitat of A. aegypti. The range of the disease appears to be expanding possibly due to climate change.

Vaccine
In 2016 a partially effective vaccine for dengue fever became commercially available in the Philippines and Indonesia. It has also been approved for use by Mexico, Brazil, El Salvador, Costa Rica, Singapore, and Paraguay. In Indonesia it costs about US$207 for the recommended three doses.

The vaccine is produced by Sanofi and goes by the brand name Dengvaxia. It is based on a weakened combination of the yellow fever virus and each of the four dengue serotypes. Two studies of a vaccine found it was 60% effective and prevented more than 80 to 90% of severe cases. This is less than wished for by some. In 2017 the manufacturer recommended that the vaccine only be used in people who have previously had a dengue infection as otherwise there was evidence it may worsen subsequent infections.

There are ongoing programs working on a dengue vaccine to cover all four serotypes. Now that there is a fifth serotype this will need to be factored in. One of the concerns is that a vaccine could increase the risk of severe disease through antibody-dependent enhancement (ADE). The ideal vaccine is safe, effective after one or two injections, covers all serotypes, does not contribute to ADE, is easily transported and stored, and is both affordable and cost-effective.

Management
There are no specific antiviral drugs for dengue; however, maintaining proper fluid balance is important. Treatment depends on the symptoms. Those who are able to drink, are passing urine, have no “warning signs” and are otherwise healthy can be managed at home with daily follow-up and oral rehydration therapy. Those who have other health problems, have “warning signs”, or cannot manage regular follow-up should be cared for in hospital. In those with severe dengue care should be provided in an area where there is access to an intensive care unit.

Intravenous hydration, if required, is typically only needed for one or two days. In children with shock due to dengue a rapid dose of 20 mL/kg is reasonable. The rate of fluid administration is then titrated to a urinary output of 0.5–1 mL/kg/h, stable vital signs and normalization of hematocrit. The smallest amount of fluid required to achieve this is recommended.

Invasive medical procedures such as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk. Paracetamol (acetaminophen) is used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding. Blood transfusion is initiated early in people presenting with unstable vital signs in the face of a decreasing hematocrit, rather than waiting for the hemoglobin concentration to decrease to some predetermined “transfusion trigger” level. Packed red blood cells or whole blood are recommended, while platelets and fresh frozen plasma are usually not. There is not enough evidence to determine if corticosteroids have a positive or negative effect in dengue fever.

During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload. If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed. If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation.

History
The first record of a case of probable dengue fever is in a Chinese medical encyclopedia from the Jin Dynasty (265–420 AD) which referred to a “water poison” associated with flying insects. The primary vector, A. aegypti, spread out of Africa in the 15th to 19th centuries due in part to increased globalization secondary to the slave trade. There have been descriptions of epidemics in the 17th century, but the most plausible early reports of dengue epidemics are from 1779 and 1780, when an epidemic swept across Asia, Africa and North America. From that time until 1940, epidemics were infrequent.

In 1906, transmission by the Aedes mosquitoes was confirmed, and in 1907 dengue was the second disease (after yellow fever) that was shown to be caused by a virus. Further investigations by John Burton Cleland and Joseph Franklin Siler completed the basic understanding of dengue transmission.

The marked spread of dengue during and after the Second World War has been attributed to ecologic disruption. The same trends also led to the spread of different serotypes of the disease to new areas, and to the emergence of dengue hemorrhagic fever. This severe form of the disease was first reported in the Philippines in 1953; by the 1970s, it had become a major cause of child mortality and had emerged in the Pacific and the Americas. Dengue hemorrhagic fever and dengue shock syndrome were first noted in Central and South America in 1981, as DENV-2 was contracted by people who had previously been infected with DENV-1 several years earlier.

Etymology
The origins of the Spanish word dengue are not certain, but it is possibly derived from dinga in the Swahili phrase Ka-dinga pepo, which describes the disease as being caused by an evil spirit. Slaves in the West Indies having contracted dengue were said to have the posture and gait of a dandy, and the disease was known as “dandy fever”.

The term “break-bone fever” was applied by physician and United States Founding Father Benjamin Rush, in a 1789 report of the 1780 epidemic in Philadelphia. In the report title he uses the more formal term “bilious remitting fever”. The term dengue fever came into general use only after 1828. Other historical terms include “breakheart fever” and “la dengue”. Terms for severe disease include “infectious thrombocytopenic purpura” and “Philippine”, “Thai”, or “Singapore hemorrhagic fever”.

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