Challenges in Reducing Dengue Burden

Diagnostics, Control Measures and Vaccines

Sai Kit Lam

Disclosures

Expert Rev Vaccines. 2013;12(9):995-1010. 

In This Article

Epidemiology

Dengue is considered to be the most important mosquito-borne viral disease in the world today, with the incidence of dengue increasing 30-fold over the last 50 years.[202] The virus is prevalent in tropical and subtropical regions, placing an estimated 2.5 billion people at risk of transmission in over 100 endemic countries in the Asia–Pacific region, the Americas, the Middle East and Africa.[1] It is estimated that 50–100 million infections occur annually worldwide. This results in 500,000 cases of severe dengue, mainly affecting children, leading to a case–fatality rate of up to 2.5%.[204] Figure 1 shows the number of dengue cases reported to the WHO, and of countries reporting dengue between 1955 and 2007.[205]

Figure 1.

Average annual number of dengue cases reported to the WHO, and of countries reporting dengue, 1955–2007.
Adapted with permission from [205]. © WHO 2009.

Over 70% of the population at risk for dengue worldwide live in the South-East Asian and Western Pacific regions, which experience nearly 75% of the global burden of disease due to dengue.[205]

The increasing number of countries reporting dengue cases in the past decade reflects the increased spread of the disease, particularly in the WHO South-East Asia region. Of the 11 countries in the region, cases were reported in 8 in 2003, rising to 10 by 2006, with North Korea the only country not to report dengue.[206] The majority of cases were reported in Indonesia and Thailand, each reporting 57 and 23% of cases in the region, respectively. Many of these cases are re-infections, reflecting the hyperendemicity of dengue in this area. For example, a report on dengue revealed that 87% of dengue cases in Thailand were due to re-infections, and only 11% were as a result of primary infections.[7] Outbreaks of dengue have also been reported in India, Sri Lanka and the Maldives.[8] A large outbreak in Delhi in 1996, resulting in more than 16,000 dengue cases and more than 550 deaths, brought the impact of dengue to the attention of the Indian government. Dengue was subsequently declared a dangerous disease under the Delhi Municipal Act.[8,207]

Dengue cases have also risen in the WHO Western Pacific region.[204] The number of dengue infections reported annually has increased from 100,000 during 2001–2002 to between 150,000 and 170,000 during 2003–2006. Since 2007, over 200,000 dengue cases each year have been reported in the region. The majority of cases have occurred in Vietnam, the Philippines, Malaysia and Cambodia. Overall in 2011, 200,779 cases and 746 deaths were reported in these four countries.[208]

Over the last decade, the Americas have also reported a dramatic increase in the number of reported dengue cases, rising from 1,033,417 in the 1980s, to 2,725,405 in the 1990s and 4,759,007 between 2000 and 2007,[9] with all of the four dengue serotypes circulating in the region.[209] A similar trend was observed for the number of DHF cases. In 2011 (up to epidemiological week 50), over 1 million cases of dengue fever (DF) were reported throughout many of the Latin American countries, with over 18,321 cases of severe dengue and 716 deaths.[210] Between 2001 and 2009, six countries – Venezuela, Brazil, Costa Rica, Colombia, Honduras and Mexico – accounted for more than 75% of all cases in the region,[10] the majority of which were reported in Brazil.[9] Changes in the age group profile of the disease were also identified in Brazil, where dengue has been historically characterized by a higher incidence among adults.[11] However, in the 2007 epidemic, children were affected predominantly with severe dengue, more closely resembling the epidemiological profile in South-East Asia. This trend has since continued in Brazil and is attributed to the recirculation of an individual viral serotype, serotype 2, which had originally infected adults.[12] Since its reappearance in 2007, the serotype affected susceptible individuals, that is, children, who could not have been infected with that particular serotype during its initial circulation.

Dengue has been documented in Africa, but poor surveillance data have meant reliance on serosurveys and traveler information.[205] Available data suggest that dengue is endemic to 34 countries across all regions of Africa, with all four DENV serotypes in co-circulation and DENV2 reported to cause the most epidemics.[13,14] Interestingly, it appears that Black patients are less susceptible to severe dengue disease, as seen during a 1981 epidemic in Cuba.[15,16]

New research indicates that the true prevalence of dengue may be even higher than previous estimates. A recent study used a formal modeling framework to map the global distribution of dengue risk and to predict the public health burden of dengue, based on the global population in 2010.[17] The results estimate that the number of annual dengue infections is 390 million, more than three times the WHO estimate.[17]

Factors Involved in the Rise of Dengue Incidence

The increase in incidence and disease severity is attributed partly to the geographic spreading of the mosquito vector, leading to the increased co-circulation of all four dengue serotypes in urban areas.[1] A number of other related parameters are considered to contribute to the spread and activity of the vector, including: increased temperature and precipitation, in which mosquitoes thrive; and rapid population growth as a result of rural to urban migration, leading to uncontrolled urbanization.[18,19] Furthermore, an unreliable water supply leads to an increase in water storage in containers and in the volume of solid waste, providing an abundance of larval habitats in urban areas.[20] Geographical expansion of the mosquito has been facilitated by international commercial trade, particularly in used tires, which accumulate rainwater easily. Furthermore, there has been a lack of political will, and limited financial and human resources to implement effective control measures.[20] These factors have been implicated in a re-emergence of dengue in Latin America in 1967, after many countries in the region were certified as being free of the virus's mosquito vector between 1952 and 1965 as a result of vector control efforts.[20]

International travel is being implicated increasingly in the dissemination of dengue.[205] It is estimated that up to 2% of all travelers returning home with an illness have DF.[21] This figure is higher in travelers returning from the tropics with a febrile illness, with dengue increasing from 2% in the early 1990s to 16% by 2005.[22] Dengue is now a more common cause of febrile illness in travelers returning from South-East Asia than malaria.[23]

Geographic Spread to New Areas

Travelers also contribute to the spread of dengue to new, traditionally dengue-free regions, such as Europe, the USA and Australia.[24,25,211] Dengue-infected travelers returning home can place the local population at risk of further spread of the disease, wherever the mosquito vectors are present, establishing autochthonous cycles of infection.[22,205] The increasing global spread of the vector means that many non-endemic countries harbor populations of mosquitoes capable of spreading the dengue virus introduced by infected returning travelers.[22]

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