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Epidemic Dengue/Dengue Haemorrhagic Fever: a Global Public Health Problem in the 21St Century*

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Epidemic Dengue/Dengue Haemorrhagic Fever: a Global Public Health Problem in the 21St Century* Epidemic Dengue/Dengue Haemorrhagic Fever: A Global Public Health Problem in the 21st Century* By Duane J. Gubler Division of Vector-Borne Infectious Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Public Health Service U.S. Department of Health and Human Services PO Box 2087, Fort Collins, CO 80522 Tel: (970) 221-6428, Fax: (970) 22106476 E-mail: [email protected] Abstract Dengue/dengue haemorrhagic fever has been one of the most important resurgent tropical diseases in the past 17 years, with expanding geographical distribution of both the viruses and the mosquito vectors, increased frequency of epidemics, development of hyperendemicity (co- circulation of multiple virus serotypes) and the emergence of dengue haemorrhagic fever in new areas. This paper briefly reviews the changing epidemiology of dengue, discusses some of the factors responsible for the recent resurgence, and reviews the current options available for reversing the emerging trend of the disease. Introduction with each of the four dengue serotypes during their lifetime. Dengue fever/dengue haemorrhagic fever (DF/DHF) is caused by infection with four Epidemic dengue fever is a very old dengue virus serotypes DEN-1, DEN-2, disease, but it was characterized during DEN-3 and DEN-4, which are closely most of its history by periodic, often related to each other antigenically(9). This infrequent, epidemics. In the past results in extensive cross-reactivity in 17 years, however, there has been a serological tests, but infection with one dramatic resurgence of epidemic dengue serotype does not provide cross-protective activity in the tropics worldwide. This immunity against the others; thus, persons increased epidemic activity, which has living in an endemic area can be infected been caused by all four virus serotypes, has been associated with the * This paper was published recently in Emerging Infections 1, Chapter 1, pp 1-14, W.M. Scheld, D. Armstrong and J.M. Hughes, editors, ASM Press, Washington DC, 1997. Dengue Bulletin – Vol 21, 1997 1 Dengue/Dengue Haemorrhagic Fever: A Global Public Health Problem geographical expansion of both the During this acute febrile period, which may mosquito vectors and the viruses, the be as short as 2 days and as long as 10 development of hyperendemicity (the co- days, there is a viremia, which may vary in circulation of multiple virus serotypes in an magnitude and duration(6,7). If uninfected area), and the emergence of dengue Ae. aegypti mosquitoes bite the ill person haemorrhagic fever. Hyperendemicity is the during this febrile viremic stage, those most constant factor associated with the mosquitoes may become infected and evolution of epidemic DHF in a geographical subsequently may transmit the virus to area. other, uninfected persons after an extrinsic incubation period of 8 to 12 days(9). This paper reviews the changing epidemiology associated with dengue viruses and attempts to explain why such Clinical presentation changes have occurred in the waning Dengue virus infection in humans of all years of the 20th century. four virus serotypes causes a spectrum of illness ranging from inapparent or mild febrile illness to severe and fatal haemor- Transmission cycle rhagic disease. Clinical presentation in both children and adults may vary in Infection with dengue viruses is severity, depending on the strain and transmitted through the bite of infective serotypes of the infecting virus, and the female Aedes spp. mosquitoes(9). Aedes immune status, age and the genetic aegypti, the principal vector, is a small background of the patient. In dengue black-and-white, highly domesticated endemic areas, acute dengue infections mosquito that prefers to lay its eggs in are often clinically nonspecific, especially artificial water-containers commonly found in children, with signs and symptoms of a in urban areas of the tropics. Containers viral syndrome. found in and around the home, such as those used for water storage, flower Classical dengue fever is primarily a vases, old automobile tyres, buckets and disease of older children and adults, other junk items that collect rainwater are characterized by a sudden onset of fever examples. The adult mosquitoes are and one or more of a number of non- rarely noticed, preferring to rest indoors specific signs and symptoms such as frontal and to feed on humans during daylight headache, retro-orbital pain, myalgias, hours in an unobtrusive and often arthralgias, nausea and vomiting, weakness undetected way. (1,9,31) and rash . Anorexia, altered taste sensation and mild sore throat are not Infection with dengue viruses occurs uncommon. Clinical laboratory findings when a person is bitten by an infective associated with dengue fever include mosquito. After a period of incubation leukopenia, and, in some patients, lasting 3 to 14 days (average 4 to 6 days), thrombocytopenia and elevated liver the person may experience an acute enzymes. Haemorrhagic manifesta-tions onset of fever accompanied by a variety of may occur, the most common being skin non-specific signs and symptoms(31). 2 Dengue Bulletin – Vol 21, 1997 Dengue/Dengue Haemorrhagic Fever: A Global Public Health Problem haemorrhages. Dengue fever is generally self-limiting and rarely fatal, the acute illness incidence lasting 3 to 7 days. Convale-scence, Dengue fever and Ae. aegypti mosquitoes however, may be prolonged for weeks with have a worldwide distribution in the weakness and depression. No permanent tropical areas of the world, with over 2.5 sequelae are known, and immunity for the billion people living in dengue endemic infecting virus serotype is lifelong. areas (Figure 1)(13,17,29). The currently Dengue haemorrhagic fever is known geographical distribution of the primarily a disease of children under 15 various dengue virus serotypes is shown years of age, although it may occur in in Figure 2, and reflects the development older children and adults as well. Like of hyperendemicity in most tropical areas dengue fever, it is characterized by a of the world in the past 15-20 years. In sudden onset of fever and non-specific 1997, DF/DHF has been the most important signs and symptoms, and is difficult to arboviral disease of humans, with an distinguish from dengue fever and other estimated 50 to 100 million cases of dengue illnesses during the acute stage. The fever and several hundred thousand cases critical stage in DHF occurs at the time of of DHF occurring each year, depending on defervescence when the patient develops epidemic activity(13,14,24). Currently, DHF is a a capillary-leak syndrome, with signs of leading cause of hospitalization and death circulatory failure and haemorrhagic among children in many south-east Asian manifestations, primarily skin haemor- countries where epidemics first occurred 3 rhages. Thrombocytopenia (<100 000/mm ) in the 1950s(1). Epidemic DHF spread to and elevated haematocrit are prominent the South Pacific islands in the 1970s, and features. DHF can be a very dramatic reached the Caribbean Basin in the disease with the patient’s condition 1980s(8,13,14). The pattern of severe deteriorating very rapidly with the onset of haemorrhagic disease has evolved in the shock and resulting in death if the plasma American region in the 1980s and 1990s leakage is not detected and corrected with in a manner similar to the way it did in fluid replacement therapy. Leukopenia, south-east Asia in the 1960s and thrombocytopenia and haemoconcen- 1970s(8,12). In Central and South America, tration are constant findings; hepatomegaly dengue fever has an economic impact of and elevated liver enzymes are common. the same order and magnitude as malaria, Risk factors for developing severe tuberculosis, sexually transmitted diseases haemorrhagic disease are not fully under- (excluding AIDS), hepatitis, the childhood stood, but, as noted above, include the cluster (polio, measles, pertussis, strain and serotype of the infecting diphtheria) and the tropical cluster dengue virus, the immune status, age and (schistosomiasis, filariasis, Chagas’ genetic background of the patient. disease, leishmaniasis and onchocerciasis)(23). Geographical distribution and Dengue Bulletin – Vol 21, 1997 3 Dengue/Dengue Haemorrhagic Fever: A Global Public Health Problem Figure 1. Global distribution of epidemic dengue and the principal vector mosquito, Aedes aegypti, 1997 Figure 2. Known global distribution of the four dengue virus serotypes, showing areas of hyperendemicity, 1997 4 Dengue Bulletin – Vol 21, 1997 Dengue/Dengue Haemorrhagic Fever: A Global Public Health Problem Changing epidemiology and dengue viruses thrived in this new ecological setting, with increased trans- The epidemiology of dengue viruses mission and increased frequency of dengue changed with the ecological disruption in epidemics occurring in the indigenous south-east Asia during and following populations of children. Moreover, economic World War II(9,18). During the war, existing expansion began in the region that water systems were destroyed, and water continues even today. This led to continued storage was increased for domestic use urbanization and increased movement of as well as for fire control. War equipment people (and with them, of dengue viruses) was moved between cities and countries, between cities and countries. Those and large amounts of equipment were countries that did not already have multiple also left behind. This material collected virus serotypes co-circulating quickly rainwater and made ideal larval
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