Dengue Fever, what you should know…


Seeing that it is currently spreading in Belize we thought it would be a good topic to post today. Educating yourself on this disease will prove to be beneficial to you and the people around you. We tend to depend on the health departments to figure out ways ensure we are safe from these diseases, however it should fall on us to ensure that our neighborhoods are safe and clean and that we do not provide places for mosquitoes to breed. Like everything else we must take this matter seriously and make the first step to prevent it from spreading.

 

Dengue (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus. Infection with one of these serotypes provides immunity to only that serotype for life, so persons living in a dengue-endemic area can have more than one dengue infection during their lifetime. DF and DHF are primarily diseases of tropical and sub tropical areas, and the four different dengue serotypes are maintained in a cycle that involves humans and the Aedes mosquito. However, Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain of the infecting virus, as well as the age, and especially the prior dengue infection history of the patient.

 

The first reported epidemics of DF occurred in 1779-1780 in Asia, Africa, and North America.  The near simultaneous occurrence of outbreaks on three continents indicates that these viruses and their mosquito vector have had a worldwide distribution in the tropics for more than 200 years. During most of this time, DF was considered a mild, nonfatal disease of visitors to the tropics. Generally, there were long intervals (10-40 years) between major epidemics, mainly because the introduction of a new serotype in a susceptible population occurred only if viruses and their mosquito vector could survive the slow transport between population centers by sailing vessels.

 

A TEM micrograph showing Dengue virus virions ...

A TEM micrograph showing Dengue virus virions (the cluster of dark dots near the center). Español: Partículas maduras del virus del Dengue-2 replicándose en un cultivo tisular de cinco días. La magnificación original es de 123,000 veces. Deutsch: Eine TEM-Aufnahme, welche Dengue-2-Virus Virionen zeigt (schwarze Punkte in der Mitte). (Photo credit: Wikipedia)

 

A pandemic of dengue began in Southeast Asia after World War II and has spread around the globe since then.  Epidemics caused by multiple serotypes (hyperendemicity) are more frequent, the geographic distribution of dengue viruses and their mosquito vectors has expanded, and DHF has emerged in the Pacific region and the Americas. In Southeast Asia, epidemic DHF first appeared in the 1950s, but by 1975 it had become a frequent cause of hospitalization and death among children in many countries in that region.

 

The emergence of dengue/DHF as a major public health problem has been most dramatic in the American region. In an effort to prevent urban yellow fever, which is also transmitted by Ae. aegypti, the Pan American Health Organization started a campaign that eradicated Ae. aegypti from most Central and South American countries in the 1950s and 1960s. As a result, epidemic dengue occurred only sporadically in some Caribbean islands during this period.

 

The reasons for the dramatic global emergence of DF/DHF as a major public health problem are complex and not well understood. However, several important factors can be identified.

 

  1. First, major global demographic changes have occurred, the most important of which have been uncontrolled urbanization and concurrent population growth. These demographic changes have resulted in substandard housing and inadequate water, sewer, and waste management systems, all of which increase Ae. aegypti population densities and facilitate transmission of Ae. aegypti-borne disease.
  2. In most countries the public health infrastructure has deteriorated. Limited financial and human resources and competing priorities have resulted in a “crisis mentality” with emphasis on implementing so-called emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission. This approach has been particularly detrimental to dengue control because, in most countries, surveillance is passive; the system to detect increased transmission normally relies on reports by local physicians who often do not consider dengue in their differential diagnoses. As a result, an epidemic has often reached or passed its peak before it is recognized.
  3. Increased travel by airplane provides the ideal mechanism for infected human transport of dengue viruses between population centers of the tropics, resulting in a frequent exchange of dengue viruses and other pathogens.
  4. Lastly, effective mosquito control is virtually nonexistent in most dengue-endemic countries. Considerable emphasis in the past has been placed on ultra-low-volume insecticide space sprays for adult mosquito control, a relatively ineffective approach for controlling Ae. aegypti.

 

No dengue vaccine is available. Recently, however, attenuated candidate vaccine viruses have been developed.  Efficacy trials in human volunteers have yet to be initiated.  Research is also being conducted to develop second-generation recombinant vaccine viruses. Therefore, an effective dengue vaccine for public use will not be available for 5 to 10 years.

 

Signs and symptoms

 

The disease manifests as a sudden onset of severe headache, muscle and joint pains (myalgias and arthralgias—severe pain that gives it the nick-name break-bone fever or bonecrusher disease), fever, and rash. The dengue rash is characteristically bright red petechiae and usually appears first on the lower limbs and the chest; in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting, or diarrhea. Some cases develop much milder symptoms which can be misdiagnosed as influenza or other viral infection when no rash is present. Thus travelers from tropical areas may pass on dengue in their home countries inadvertently, having not been properly diagnosed at the height of their illness. Patients with dengue can pass on the infection only through mosquitoes or blood products and only while they are still febrile. The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the disease (the so-called biphasic pattern). Clinically, the platelet count will drop until the patient’s temperature is normal. Cases of DHF also show higher fever, variable haemorrhagic phenomena, thrombocytopenia, and haemoconcentration. A small proportion of cases lead to dengue shock syndrome (DSS) which has a high mortality rate. DHF combined with a cirrhotic liver has been suspected in rapid development of hepatocellular carcinoma (HCC). Given that the Dengue virus (DEN) is related to the Hepatitis C virus, this is an avenue for further research as HCC is among the top five cancerous causes of death outside Europe and North America. Normally HCC does not occur in a cirrhotic liver for ten or more years after the cessation of the poisoning agent. DHF patients can develop HCC within one year of cessation of abuse.

 

Treatment

 

The mainstay of treatment is timely supportive therapy to tackle shock due to haemoconcentration and bleeding. Close monitoring of vital signs in critical period (between day 2 to day 7 of fever) is critical. Increased oral fluid intake is recommended to prevent dehydration. Supplementation with intravenous fluids may be necessary to prevent dehydration and significant concentration of the blood if the patient is unable to maintain oral intake. A platelet transfusion is indicated in rare cases if the platelet level drops significantly (below 20,000) or if there is significant bleeding. The presence of melena may indicate internal gastrointestinal bleeding requiring platelet and/or red blood cell transfusion.

 

Aspirin and non-steroidal anti-inflammatory drugs should be avoided as these drugs may worsen the bleeding tendency associated with some of these infections. Patients may receive paracetamol preparations to deal with these symptoms if dengue is suspected.

 

Traditional and emerging treatments

 

Emerging evidence suggests that mycophenolic acid and ribavirin inhibit dengue replication. Initial experiments showed a fivefold increase in defective viral RNA production by cells treated with each drug. In vivo studies, however, have not yet been done. Unlike HIV therapy, lack of adequate global interest and funding greatly hampers the development of treatment regime.

 

In Brazilian traditional medicine, dengue is treated with cat’s claw herb, which is for inflammation and does not prevent dengue.

 

In Malaysia, dengue is treated by some using natural medicine. Mas Amirtha and Semalu developed by the Alternative Medicine Research Institute, Center for Asia. The treatment is speculated to be able to arrest and reverse the viral infection and prevent the disease from advancing into a critical stage, though no evidence has yet shown effectiveness. In Philippines dengue patients use tawa-tawa herbs and sweet-potato-tops juice to increase the platelets counts and revived the patients.

 

Control

 

Primary prevention of dengue mainly resides in mosquito control. There are two primary methods: larval control and adult mosquito control.[citation needed] In urban areas, Aedes mosquitos breed on water collections in artificial containers such as plastic cups, used tires, broken bottles, flower pots, etc. Periodic draining or removal of artificial containers is the most effective way of reducing the breeding grounds for mosquitos.[citation needed] Larvicide treatment is another effective way to control the vector larvae but the larvicide chosen should be long-lasting and preferably have World Health Organization clearance for use in drinking water. There are some very effective insect growth regulators (IGRs) available which are both safe and long-lasting (e.g. pyriproxyfen). For reducing the adult mosquito load, fogging with insecticide is somewhat effective.[citation needed]

 

Prevention of mosquito bites is another way of preventing disease. This can be achieved by using insect repellent, mosquito traps or mosquito nets.

 

 

PerspectivesDengue (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus. Infection with one of these serotypes provides immunity to only that serotype for life, so persons living in a dengue-endemic area can have more than one dengue infection during their lifetime. DF and DHF are primarily diseases of tropical and sub tropical areas, and the four different dengue serotypes are maintained in a cycle that involves humans and the Aedes mosquito. However, Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain of the infecting virus, as well as the age, and especially the prior dengue infection history of the patient.History of DengueThe first reported epidemics of DF occurred in 1779-1780 in Asia, Africa, and North America.  The near simultaneous occurrence of outbreaks on three continents indicates that these viruses and their mosquito vector have had a worldwide distribution in the tropics for more than 200 years. During most of this time, DF was considered a mild, nonfatal disease of visitors to the tropics. Generally, there were long intervals (10-40 years) between major epidemics, mainly because the introduction of a new serotype in a susceptible population occurred only if viruses and their mosquito vector could survive the slow transport between population centers by sailing vessels.A pandemic of dengue began in Southeast Asia after World War II and has spread around the globe since then.  Epidemics caused by multiple serotypes (hyperendemicity) are more frequent, the geographic distribution of dengue viruses and their mosquito vectors has expanded, and DHF has emerged in the Pacific region and the Americas. In Southeast Asia, epidemic DHF first appeared in the 1950s, but by 1975 it had become a frequent cause of hospitalization and death among children in many countries in that region.Current TrendsIn the 1980s, DHF began a second expansion into Asia when Sri Lanka, India, and the Maldive Islands had their first major DHF epidemics; Pakistan first reported an epidemic of dengue fever in 1994. The epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes, but DEN-3 was predominant and was genetically distinct from DEN-3 viruses previously isolated from infected persons in those countries. After an absence of 35 years, epidemic dengue fever reemerged in both Taiwan and the People’s Republic of China in the 1980s. The People’s Republic of China had a series of epidemics caused by all four serotypes, and its first major epidemic of DHF, caused by DEN-2, was reported on Hainan Island in 1985. Singapore also had a resurgence of dengue/DHF from 1990 to 1994 after a successful control program had prevented significant transmission for over 20 years. In other countries of Asia where DHF is endemic, the epidemics have become progressively larger in the last 15 years.

In the Pacific, dengue viruses were reintroduced in the early 1970s after an absence of more than 25 years. Epidemic activity caused by all four serotypes has intensified in recent years with major epidemics of DHF on several islands.

Despite poor surveillance for dengue in Africa, epidemic dengue fever caused by all four serotypes has increased dramatically since 1980. Most activity has occurred in East Africa, and major epidemics were reported for the first time in the Seychelles (1977), Kenya (1982, DEN-2), Mozambique (1985, DEN-3), Djibouti (1991-92, DEN-2), Somalia (1982, 1993, DEN-2), and Saudi Arabia (1994, DEN-2). Epidemic DHF has not been reported in Africa or the Middle East, but sporadic cases clinically compatible with DHF have been reported from Mozambique, Djibouti, and Saudi Arabia.

The emergence of dengue/DHF as a major public health problem has been most dramatic in the American region. In an effort to prevent urban yellow fever, which is also transmitted by Ae. aegypti, the Pan American Health Organization started a campaign that eradicated Ae. aegypti from most Central and South American countries in the 1950s and 1960s. As a result, epidemic dengue occurred only sporadically in some Caribbean islands during this period. The Ae. aegypti eradication program, which was officially discontinued in the United States in 1970, gradually weakened elsewhere, and the mosquito began to reinfest countries from which it had been eradicated. As a result, the geographic distribution of Ae. aegypti in 2002 was much wider than that before the eradication program (Figure 1).

Figure 1. Distribution of Aedes aegypti (red shaded areas) in the Americas in 1970, at the end of the mosquito eradication program, and in 2002.

In 1970, only DEN-2 virus was present in the Americas, although DEN-3 may have had a focal distribution in Colombia and Puerto Rico. In 1977, DEN-1 was introduced and caused major epidemics throughout the region over a 16-year period. DEN-4 was introduced in 1981 and caused similar widespread epidemics. Also in 1981, a new strain of DEN-2 from Southeast Asia caused the first major DHF epidemic in the Americas (Cuba). This strain has spread rapidly throughout the region and has caused outbreaks of DHF in Venezuela, Colombia, Brazil, French Guiana, Suriname, and Puerto Rico. By 2003, 24 countries in the American region had reported confirmed DHF cases (Figure 2), and DHF is now endemic in many of these countries.

Figure 2. American countries with laboratory-confirmed dengue hemorrhagic fever (red shaded areas), prior to 1981 and from 1981 to 2003.

DEN-3 virus reappeared in the Americas after an absence of 16 years. This serotype was first detected in association with a 1994 dengue/DHF epidemic in Nicaragua. Almost simultaneously, DEN-3 was confirmed in Panama and, in early 1995, in Costa Rica.

Viral envelope gene sequence data from the DEN-3 strains isolated from Panama and Nicaragua have shown that this new American DEN-3 virus strain was likely a recent introduction from Asia since it is genetically distinct from the DEN-3 strain found previously in the Americas, but is identical to the DEN-3 virus serotype that caused major DHF epidemics in Sri Lanka and India in the 1980s. As suggested by the finding of a new DEN-3 strain, and the susceptibility of the population in the American tropics to it DEN-3 spread rapidly throughout the region causing major epidemics of dengue/DHF in Central America in 1995.

Figure 3. Presence of DEN-3 in the Americas from 1994 to 2003

In 2005, dengue is the most important mosquito-borne viral disease affecting humans; its global distribution is comparable to that of malaria, and an estimated 2.5 billion people live in areas at risk for epidemic transmission (Figure 4). Each year, tens of millions of cases of DF occur and, depending on the year, up to hundreds of thousands of cases of DHF. The case-fatality rate of DHF in most countries is about 5%, but this can be reduced to less than 1% with proper treatment.  Most fatal cases are among children and young adults.

Figure 4. World distribution of dengue viruses and their mosquito vector, Aedes aegypti, in 2008.

There is a small risk for dengue outbreaks in the continental United States. Two competent mosquito vectors, Ae. aegypti and Aedes albopictus, are present and, under certain circumstances, each could transmit dengue viruses. This type of transmission has been detected six times in the last 25 years in south Texas (1980 -2004) and has been associated with dengue epidemics in northern Mexico by Aedes aegypti and in Hawaii (2001-02) due to Ae. albopictus.  Moreover, numerous viruses are introduced annually by travelers returning from tropical areas where dengue viruses are endemic. From 1977 to 2004, a total of 3,806 suspected cases of imported dengue were reported in the United States. Although some specimens collected were not adequate for laboratory diagnosis, 864 (23%) cases were confirmed as dengue. Many more cases probably go unreported each year because surveillance in the United States is passive and relies on physicians to recognize the disease, inquire about the patient’s travel history, obtain proper diagnostic samples, and report the case. These data suggest that states in southern and southeastern United States, where Ae. aegypti is found, are at risk for dengue transmission and sporadic outbreaks.

Although travel-associated dengue and limited outbreaks do occur in the continental United States, most dengue cases in US citizens occur as endemic transmission among residents in some of the US territories. CDC conducts laboratory-based passive surveillance in Puerto Rico in collaboration with the Puerto Rico Department of Health. The weekly surveillance report from this collaboration can be found at: Dengue Surveillance Report

The reasons for the dramatic global emergence of DF/DHF as a major public health problem are complex and not well understood. However, several important factors can be identified.

1. First, major global demographic changes have occurred, the most important of which have been uncontrolled urbanization and concurrent population growth. These demographic changes have resulted in substandard housing and inadequate water, sewer, and waste management systems, all of which increase Ae. aegypti population densities and facilitate transmission of Ae. aegypti-borne disease.
2. In most countries the public health infrastructure has deteriorated. Limited financial and human resources and competing priorities have resulted in a “crisis mentality” with emphasis on implementing so-called emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission. This approach has been particularly detrimental to dengue control because, in most countries, surveillance is (just as in the U.S.) passive; the system to detect increased transmission normally relies on reports by local physicians who often do not consider dengue in their differential diagnoses. As a result, an epidemic has often reached or passed its peak before it is recognized.
3. Increased travel by airplane provides the ideal mechanism for infected human transport of dengue viruses between population centers of the tropics, resulting in a frequent exchange of dengue viruses and other pathogens.
4. Lastly, effective mosquito control is virtually nonexistent in most dengue-endemic countries. Considerable emphasis in the past has been placed on ultra-low-volume insecticide space sprays for adult mosquito control, a relatively ineffective approach for controlling Ae. aegypti.

Future Outlook

No dengue vaccine is available. Recently, however, attenuated candidate vaccine viruses have been developed.  Efficacy trials in human volunteers have yet to be initiated.  Research is also being conducted to develop second-generation recombinant vaccine viruses. Therefore, an effective dengue vaccine for public use will not be available for 5 to 10 years.

Prospects for reversing the recent trend of increased epidemic activity and geographic expansion of dengue are not promising. New dengue virus strains and serotypes will likely continue to be introduced into many areas where the population densities of Ae. aegypti are at high levels. With no new mosquito control technology available, in recent years public health authorities have emphasized disease prevention and mosquito control through community efforts to reduce larval breeding sources. Although this approach will probably be effective in the long run, it is unlikely to impact disease transmission in the near future. We must, therefore, develop improved, proactive, laboratory-based surveillance systems that can provide early warning of an impending dengue epidemic. At the very least, surveillance results can alert the public to take action and physicians to diagnose and properly treat DF/DHF cases.

 

 

 

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