Background of the disease

In recent years dengue fever (DF) has become a major international health problem affecting tropical and sub-tropical regions around the world - especially urban and peri-urban areas. The geographic distribution of dengue, the frequency of epidemic cycles, and the number of cases of dengue have increased sharply during the last two decades. In addition, the frequency of a potentially lethal complication of dengue, called dengue haemorrhagic fever (DHF) has begun to occur on a regular basis in countries where only dengue occurred previously.

Dengue fever is caused by four distinct but closely related dengue viruses called serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) and transmitted to humans through the bites of infected mosquitos (Aedes aegypti is the primary vector).

Dengue fever is a severe flu-like illness that affects infants, young children and adults, but rarely causes death. Symptoms vary according to age. Infants and young children may be asymptomatic or have undifferentiated fever and rash, whereas older children or adults are more likely to have a more severe set of symptoms including high fever that starts quickly, sometimes with two peaks, and/or severe headache, pain behind the eyes, muscle and joint pains, nausea and vomiting and rash. Infection with dengue confers immunity to infection with the same dengue serotype, but aside from short-lived protection does not prevent infection with other serotypes.

DHF is a life threatening complication of dengue characterized by high fever lasting 2-7 days, haemorrhagic phenomena (including vascular leakage of plasma), low numbers of platelets and sometimes circulatory failure. The condition of some patients progresses to shock. This is known as dengue shock syndrome (DSS), which could be rapidly fatal if appropriate volume replacement therapy is not administered promptly. Without proper treatment, DHF case fatality rates can exceed 20%. With modern intensive supportive therapy, it can be reduced to less than 1%.

While the mechanisms that cause DHF are not completely understood, it is widely accepted that antibodies from previous dengue infections can predispose some individuals to develop DHF when infected by a second dengue serotype. Thus the co-circulation of several different dengue serotypes in a geographical area favours the occurrence of DHF in that area.

Transmission

Dengue viruses are transmitted to humans through the bites of infective female Aedes mosquitos. Mosquitos acquire the virus while feeding on the blood of an infected person. Once infected, a mosquito is capable of transmitting the virus to susceptible individuals for the rest of its life, during probing and blood feeding. Infected female mosquitos may also transmit the virus to the next generation of mosquitos by transovarial transmission i.e. via its eggs, but the role of this in sustaining transmission of virus to humans has not yet been delineated. Humans are the main amplifying host of the virus, although studies have shown that in some parts of the world monkeys may become infected and perhaps serve as a source of virus for uninfected mosquitos. The virus circulates in the blood of infected humans for 2-7 days, at approximately the same time as they have fever; Aedes mosquitos may acquire the virus when they feed on an individual at this time.

History

Beginning with the latter part of the eighteenth century, and throughout the nineteenth and early twentieth centuries major epidemics of dengue-like illness have been reported in the Americas, southern Europe, north Africa, the eastern Mediterranean, Asia, and Australia, as well as on islands in the Indian Ocean, the south and central Pacific and the Caribbean (1). The beginning of these more frequent reports coincides with the time that the Ae. aegypti mosquito, the primary dengue vector, began spreading from Africa throughout the tropics, via sailing vessels used in commerce and in the slave trade, and when people began moving more frequently between continents. The mosquito adapted very well to urban environments, living in close proximity to people, breeding in small containers that collect rainwater and in water storage vessels.

There are a number of ecological factors associated with the middle and later parts of the twentieth century which have lead to a dramatic increase in DF, and to the emergence of DHF as a significant public health problem in the Americas and Asia. First, there has been a large increase in unplanned urbanization, resulting in large populations living in high-density areas with inadequate systems of water and solid waste management. These areas provide excellent breeding places for Ae. aegypti mosquitos.

In addition, two specific occurrences, one in Southeast Asia and the other in the Americas, were additional catalysts for the spread of dengue. First, activities associated with World War II and the immediate post-war period are particularly implicated in the increase of DF and DHF in South-East Asia. The existing water supply and sewage systems were destroyed during the war resulting in more favourable breeding places for Ae. aegypti. Second, the movement of (mostly susceptible) troops to the war theatre for short periods of time, presented the virus with a large supply of new susceptible hosts on a continuous basis, increasing the spread of disease. The subsequent movement of those hosts and or war machinery to other areas facilitated the circulation of virus serotypes throughout the region, and fostered hyperendemicity (the circulation of more than one serotype at the same time). During the post- war period millions of susceptible people from the poor rural countryside moved to the cities, providing a continuous influx of large susceptible populations living in poor peri-urban areas that were hyperendemic for dengue.

This led to both the increase in DF and the emergence of DHF as major public health problems. DHF was discovered in Manila in 1953. There had been sporadic reports of disease with symptoms similar to DHF previously, but these were considered to be unusual occurrences. Since 1953, DHF has been increasing in its frequency, geographical scope, and number of cases.

In the Americas, the lapse in mosquito eradication programmes had important consequence for dengue. The Ae. aegypti eradication programmes to fight against yellow fever were discontinued in the early 1970s. Subsequently, there was a re-infestation of the Americas with Ae. aegypti. The combination of the re-infestation of the Americas with the primary vector for dengue combined with unplanned rapid urbanization and increased travel and commerce has played an important part in the increase of dengue and emergence of DHF in the Americas.

Description of the data

For Asia, WHO has reports of cases and deaths from dengue from 1995-1998. Case reporting from the Americas is available from 1960, and reporting of deaths from 1989. There are separate reports for DF and DHF from the Americas but not from other continents. Although dengue infections occur in Africa they are not routinely reported from Africa.

Strengths and weaknesses of dengue surveillance

Dengue surveillance is difficult to establish and maintain. DF is a complex disease whose symptoms are difficult to distinguish from other common febrile illnesses. Surveillance for DHF holds special problems. First, there are many places where DHF is a rare occurrence. In these places DHF may not be suspected as a cause of particular symptoms. Second, diagnosing DHF cannot be done by clinical judgement alone. Correctly identifying a case of DHF requires laboratory tests (hemotocrits, platelet counts, virologic or serologic tests) of samples of blood collected from patients with haemorrhagic symptoms. Laboratory equipment to perform these tests are not always available in health centres.

As in other diseases the case definitions used for reporting differ among countries, and some countries report only laboratory confirmed cases whereas other report suspected cases as well. Finally, some countries report cases and deaths from DF and DHF/DSS separately, whereas in other countries reports of DF and DHF are combined. Problems of under-diagnosis, incomplete reporting and reporting delay also weaken surveillance.

Laboratories play a very important role in surveillance of dengue - not only in confirming DF and DHF cases but also in monitoring serotypes and strains circulating in the population. For example, the introduction of a new serotype may be an important indicator of future epidemics of DHF/DSS. In many countries laboratories need considerable strengthening to conduct adequate surveillance of dengue.

The lack of any systematic reports of dengue cases from Africa is a clear weakness in global surveillance efforts for dengue.

Trends

Fig 6.1 Dengue/dengue hemorrhagic fever, average annual number of cases of reported to WHO, 1955-1998