Dengue (DF) and dengue hemorrhagic fever (DHF)

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Perspectives 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.

History of Dengue 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 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 Trends In 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 2005.

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.

 

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.

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.

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.

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.

 

Glossary of terms

Endemic - means a disease occurs continuously and with predictable regularity

in a specific area or population .

Epidemic - a widespread outbreak of an infectious disease where many people

are infected at the same time.

Igm - a protein that recognizes a particular epitope on an antigen and

facilitates clearance of that antigen and is the primary antibody response to a

viral infection

Outbreak - an epidemic limited to localized increase in the incidence of a

disease, e.g., in a village, town, or closed institution

Pandemic - an epidemic occurring worldwide, or over a very wide area, crossing

international boundaries, and usually affecting a large number of people.

Recombinant vaccine - using the technique of recombination to create an

attenuated virus which elicits an immune response against the viral strain of

interest in order to use as a vaccine in humans.

Seroytpe - a closely related set of viruses that can be differiented by the

immune response they produce.

Viral envelope gene sequence - the nucleic acid composition in the envelope

gene

http://www.cdc.gov/ncidod/dvbid/dengue/

 

 

" Respect means listening until everyone has been heard and understood, only

then is there a possibility of " Balance and Harmony " the goal of Indian

Spirituality. " Dave Chief, Grandfather of Red Dog