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Dengue and dengue haemorrhagic fever
José G Rigau-Pérez, Gary G Clark, Duane J Gubler, Paul Reiter, Eduard J Sanders, A Vance Vorndam
The incidence and geographical distribution of dengue have greatly increased in recent years. Dengue is an acute mosquito-transmitted viral disease characterised by fever, headache, muscle and joint pains, rash, nausea, and vomiting. Some infections result in dengue haemorrhagic fever (DHF), a syndrome that in its most severe form can threaten the patient’s life, primarily through increased vascular permeability and shock. The case fatality rate in patients with dengue shock syndrome can be as high as 44%. For decades, two distinct hypotheses to explain the mechanism of DHF have been debated—secondary infection or viral virulence. However, a combination of both now seems to be the plausible explanation. The geographical expansion of DHF presents the need for well-documented clinical, epidemiological, and virological descriptions of the syndrome in the Americas. Biological and social research are essential to develop effective mosquito control, medications to reduce capillary leakage, and a safe tetravalent vaccine. Dengue is the most important human viral disease transmitted by arthropod vectors. Annually there are an estimated 50–100 million cases of dengue fever (DF), and 250 000 to 500 000 cases of dengue haemorrhagic fever (DHF) in the world. Over half of the world’s population live in areas at risk of infection, and these are popular tourist destinations too1,2 (figure 1). DF and DHF are caused by the four dengue viruses DEN 1, 2, 3, and 4, which are closely related antigenically. Infection with one serotype provides life-long immunity to that virus but not to the others. Dengue viruses are maintained in an urban transmission cycle in tropical and subtropical areas area by the mosquito Aedes aegypti, a species closely associated with human habitation. In some regions other Aedes species, such as Ae albopictus and Ae polynesiensis are also involved. admission and death among children in Asia.3,4 Except for a small DEN-3 outbreak in Tahiti in 1965, epidemic DF was absent from the south Pacific for 25 years. In 1971, DEN-2 was introduced, and several islands had major DF/DHF epidemics. The changes in disease pattern have been most dramatic in the American region. In the 1950s and 1960s, through the efforts of a programme coordinated by the Pan American Health Organization, most countries in central and south America were certified to have eradicated Ae aegypti. The programme was terminated in the early 1970s. By the late 1970s Ae aegypti had reinfested many locations. The number of countries with epidemic dengue increased sharply during the 1980s and 1990s as new virus strains and serotypes were introduced. In 1980, severe disease was rare, but by 1997 DHF had emerged as a disease entity in several major and many minor epidemics in tropical and subtropical countries of the Americas. The factors responsible for this global resurgence of DF and the emergence of DHF include unprecedented population growth, unplanned and uncontrolled urbanisation, increased air travel, the lack of effective mosquito control, and the deterioration, during the past 30 years, of publichealth infrastructure.1,2,5
Epidemics of an illness compatible with DF were first reported in the medical literature in 1779 and 1780, and until the 1939–45 war pandemics of DF occurred every 10–30 years. Nevertheless, recurrence of epidemic DF at any one location was infrequent. During the second world war south-east Asia experienced the co-circulation of multiple dengue virus serotypes and epidemic activity increased. With the subsequent uncontrolled growth of cities, epidemic DHF emerged as a major public-health problem in most countries of south-east Asia. The first epidemic of DHF was in 1953 (Manila) and the disease remained localised in south-east Asia through the 1970s. In the 1980s and 1990s, however, epidemic DHF spread west into India, Pakistan, Sri Lanka, and the Maldive Islands and east into China.1 DHF and dengue shock syndrome (DSS) are now a leading cause of hospital
Lancet 1998; 352: 971–77
Dengue Branch (J G Rigau MD, G G Clark PhD, P Reiter DPhil, E J Sanders MD, A V Vorndam PhD), Division of Vector-borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico; and Division of Vector-borne Infectious Diseases (D J Gubler ScD), CDC, Fort Collins, Colorado, USA Correspondence to: Dr José G Rigau-Pérez, CDC Dengue Branch, 2 calle Casia, San Juan, Puerto Rico, PR 00921-3200 (e-mail: Jor1@cdc.gov)
Dengue Dengue virus infections may be asymptomatic or lead to a range of clinical presentations, even death. The incubation period is 4–7 days (range 3–14). Typically, DF is an acute febrile illness characterised by frontal headache, retroocular pain, muscle and joint pain, nausea, vomiting, and rash.6,7 The febrile, painful period of DF lasts 5–7 days, and may leave the patient feeling tired for several more days. A biphasic or “saddleback” fever curve is not the norm. Dengue virus disappears from the blood after an average of 5 days, closely correlated with the disappearance of fever, and no carrier state ensues.8,9 The vast majority of infections, especially in children under age 15 years, are asymptomatic or minimally symptomatic.10 Population-based studies have shown increasing severity in the clinical features of DF with increasing age of the patient and with repeated
THE LANCET • Vol 352 • September 19, 1998
or hypoalbuminaemia or hypoproteinaemia. and is currently marketed in Asia (carbazochrome sodium sulphonate) did not prevent dengue vascular permeability or shock. dengue can be effectively ruled out.18 DHF is defined as an acute febrile illness with minor or major bleeding.15 If symptoms start more than two weeks after the patient has left a dengue-endemic area.22 Other severe dengue syndromes There are some unusual but well-described manifestations of dengue infection where the risk of death is high.6 Clinical findings alone are not very helpful to distinguish DF from other febrile illnesses such as the chikungunya. convulsions. and the basic clinical manifestations are similar throughout the age spectrum. In hospitals with long experience of DSS the case fatality rate in DHF can be as low as 0·2%.6.16 In the tropical Americas it is seen in all age groups. are haemorrhagic manifestations such as petechiae. A prospective study recorded pleural effusions in 84% (22/26) of DHF cases and the mean pleural effusion index (the proportion of the width of the right hemithorax occupied by a pleural effusion in the right lateral decubitus chest radiograph) was 14·1%.13.14. and encephalopathy. at the time of defervescence.7 There may be a flushing of the face.21 The four warning signs for impending shock are intense. Older children and adults may have either a mild febrile syndrome or the classical and even incapacitating disease. intravenous fluids (see below) may be all that is required for treatment. microscopic haematuria. and hypermenorrhoea.20 972 Dengue shock syndrome DSS is defined as DHF with signs of circulatory failure.15. shock.17.12. Extravasation occurs through endothelial gaps. hypotension. Once shock has set in the fatality rate may be high (12% to 44%). The development of any of these signs or any suggestion of hypotension are indications for hospital admission and management to prevent shock. or a combination of these manifestations.17 The major pathophysiological change that determines the severity of disease in DHF and differentiates it from DF is the leakage of plasma. DHF/DSS usually develop around day 3–7 of illness. a recent clinical trial showed that a drug that counteracts capillary permeability induced by histamine or hyaluronidase.4. or if the fever lasts more than two weeks. and a sudden change from fever to hypothermia with sweating and prostration. DHF and dengue shock usually develop around the third to seventh day of illness. haemorrhage. typhoid. persistent vomiting.13.6 The development of DHF provides warnings of an increased probability of shock (figure 2).24 Neurological manifestations such as altered consciousness. which is an indication for intensified observation. more commonly in children and adults with primary infections. sustained abdominal pain. or a later confluent petechial rash with round pale areas of normal skin. gingival bleeding.19 Nevertheless. gastrointestinal bleeding.10–12 Infants and young children may have an undifferentiated febrile disease with a maculopapular rash.14 Leukopenia and mild thrombocytopenia are frequent. These are DF with severe haemorrhage. where it first appeared and where it is primarily a children’s disease.7. and chest initially in the febrile period. without necrosis or inflammation of the capillary endothelium.14 When all four criteria for DHF are fulfilled. easily bruised skin. thrombocytopenia (105/L).14 Transudate due to excessive capillary permeability collects at the pleural and abdominal cavities. resulting from the leakage of plasma into serous spaces. Skin eruptions are reported in over 50% of laboratoryconfirmed dengue cases in Puerto Rico. THE LANCET • Vol 352 • September 19.18 The patient may recover rapidly after volume replacement but shock may recur during the period of excessive capillary permeability.7.17 A progressively decreasing platelet count and a rising haematocrit (signalling abnormal capillary permeability) indicate increased probability of impending shock. and evidence of plasma leakage documented by haemoconcentration (haematocrit increased by at least one-fifth or decreased by the same amount after intravenous fluid therapy). measles. The prognosis in DHF/DSS depends on prevention or early recognition and treatment of shock. 1998 .13 Less frequent. leptospirosis. and liver enzymes are usually mildly abnormal but jaundice is rare. hepatic damage. The first (and easiest information) to ascertain is the time elapsed since onset of illness. and subcutaneous bleeding at venepuncture sites are present in most cases. pleural or other effusions. The temperature is typically high (38–40°C) and continues for 2–7 days.23. neck.14 A positive tourniquet test (more than 20 petechiae in a square patch of skin 2·5ן2·5 cm [>20/in2]) may be found in over one-third of patients with DF. cardiomyopathy. epistaxis. or frank shock.SEMINAR Areas infested with Ae aegypti Countries with recent dengue activity Figure 1: World distribution of dengue infections. but not rare.6 Petechiae.4 The most common haemorrhagic feature is a positive tourniquet test (over 50% of patients). or a centrifugal maculopapular rash arising on the third or fourth day. Dengue haemorrhagic fever DHF has been most extensively studied in south-east Asia. or malaria. DHF commonly begins with a sudden rise in temperature and other symptoms resembling DF. The liver may be palpable and tender.6. restlessness or lethargy. including narrow pulse pressure (20 mm Hg).14. and coma have been ascribed to an encephalopathy secondary to prolonged DHF/DSS. Nevertheless all DHF patients need good nursing care and observation because the above changes may happen very quickly or the patient may present in a critical condition.
which are then serotyped with monoclonal antibodies in an indirect fluorescent antibody test. such as Ringer’s acetate or Ringer’s lactate. invasion of the central nervous system (viral encephalitis) is a recently documented possibility.32–34 However. Circulating virus remains detectable in the blood during the febrile period (for an average of 5 days after onset of symptoms). IgM antibody becomes detectable during the acute phase of the illness and 90% of patients are IgM positive by the sixth day after onset of symptoms. acid-base status. Because patients have loss of plasma (through increased vascular permeability into the serous spaces) they must be given isotonic solutions and plasma expanders. the PCR test is experimental and no commercial products are available. Monitoring of blood pressure. Steroids in DSS are not helpful. Currently.26 However.36 but this technique cannot reliably differentiate among the four dengue serotypes.30 Insufficient volume replacement will allow worsening shock. Commercial kits for the measurement of antibodies to dengue viruses include the standard ELISA973 Treatment Patients with DF require rest.4. extravasated fluid is rapidly resabsorbed. Vital signs should be measured every 30–60 min and haematocrit every 2–4 h. causing a drop in haematocrit. An arterial line will help in the assessment of arterial blood gases. It is used to estimate filling pressures and to guide further intravenous fluid administration. however. Monitoring should be continued for at least a day after defervescence. and dextran 40.SEMINAR Alarm signals Four criteria for DHF Fever Haemorrhagic manifestations Excessive capillary permeability Platelets р105/L Disappearance of fever Drop in platelets Increase in haematocrit Severe abdominal pain Prolonged vomiting Abrupt change from fever to hypothermia Change in level of consciousness irritability or somnolence 3–6 days after onset of symptoms Figure 2: Warning signs for dengue shock and metabolic disturbances. especially when more than 60 mL/kg of fluids has been given without improvement.23. the patient should meet the following criteria: absence of fever for 24 h (without antipyretics) and a return of appetite. urinary output. All these flaviviruses share group antigens that can cross-react in serological tests. the cells are stained with fluorescein-conjugated polyclonal antibodies to detect virus isolates. helping to identify early respiratory compromise. PCR can also detect viruses inactivated by improper storage or by complexing with neutralising antibody. but this volume is not administered uniformly throughout the 24 h.14. oral fluids to compensate for losses via diarrhoea or vomiting. Japanese. so that platelet function will not be impaired). and congestive heart failure. such as dengue and Japanese encephalitis in Asia.25.17.35 Where two flaviviruses cocirculate. A bolus of 10–20 mL of an isotonic solution per kg bodyweight is given in case of shock. the sample should be frozen at Ϫ60°C or lower. St Louis. hospital care for at least 3 days after recovery from shock.31 Use of the polymerase chain reaction (PCR) may shorten the time required for result. Plasma leakage in DHF is very rapid and the haematocrit may continue to rise even while intravenous fluids are being administered. The recommended amount of total fluid replacement in 24 h is approximately the volume required for maintenance.22 With the earliest suspicion of threatened severe illness.28 One case of nosocomial transmission from a needlestick injury has been reported. Laboratory diagnosis Dengue viruses belong to the Flaviviridae. If longer storage is needed. improvement in the clinical picture. a family which contains almost 70 viruses. plasma protein fraction. and electrolytes in the haemodynamically unstable patient. the most widely used IgM assay is a capture ELISA (enzyme-linked immunosorbent assay). and tick-borne).14. and the physician must adjust treatment using serial haematocrit.29 Placement of a central-venous-pressure line is hazardous in patients with haemorrhagic tendencies but may be necesssary. blood pressure. and is then rapidly cleared with the appearance of specific antibody. acidosis. Serological diagnosis depends on the presence of IgM antibody or a rise in IgG antibody titre in paired acute and convalescent phase sera. 1998 . then less frequently as the patient’s condition stabilises. plus replacement of 5% of bodyweight deficit. analgesics. a differential diagnosis can be made by measurement of antibody titres against these antigens separately. haemorrhagic manifestations. an intravenous line should be placed so that fluids can be provided. Once the patient begins to recover. After a week of incubation.17.17 Because convalescent-phase diagnostic samples are often difficult to obtain. platelet count.27 Vertical transmission of dengue virus has been recorded in a small number of cases. including those causing yellow fever and several encephalitides (eg. and urinary output data.4. Most laboratories attempting virus isolation utilise an established cell culture line of Ae albopictus cells. while fluid overload will produce massive effusions.18 THE LANCET • Vol 352 • September 19. respiratory compromise. Serum is the specimen of choice for both virological and serological studies. The line should be inserted by an expert in a special care area. coagulation profiles. the “leaky capillary” period is short and intravenous fluids are usually required for only 1–2 days.14. This antibody may be detectable for a median of about 60 days. and platelet count greater than 50 000/L. stable haematocrit. West Nile. and antipyretics for high fever (paracetamol [acetaminophen] but not aspirin.18 There is great variability from patient to patient. Before discharge. The virus is stable in diagnostic samples up to 5 days at 4°C. complicating diagnosis. leading to neonatal DF or even DSS. and disseminated intravasular coagulation. and level of consciousness is important. and repeated every 30 min until circulation improves and urinary output is adequate. haematocrit. a second blood sample should always be taken on the day of discharge. no respiratory distress from pleural effusion or ascites.
and blocked rain gutters. In primary dengue. and who reside in or have recently visited tropical areas. exposure to mosquitoes was common. Larvae are mostly found in artificial containers that may hold water. With acute-phase samples. These data allow for an estimate of roughly 1 illness per 1000 travellers. immunity for specific virus serotypes. flowerpots. humidity. Several mathematical models have recently explored the interactions of multiple factors that give rise to epidemic transmission in a community. but they can also be found in natural sites such as bromeliads. Dengue incidence fluctuates with the seasons and is usually associated with warmer. human behaviour.48 In over 30 000 United States troops in Somalia for three months (1993–94). and only 30 had confirmed dengue. Despite high concurrent infection rates in Thais. After the mosquito becomes infective. treeholes. the ELISA cross-reacts with other flaviviruses. mosquito population densities and survival.45–47 Disease transmission Ae aegypti is closely associated with human habitation. acquired actively by prior infection or passively by heterotypic maternal dengue IgG antibody in infants with primary infection is the most frequently reported of the probably multiple contributory causes of altered response to dengue.13 Although we have no data on the dengue incidence rate in the local populations. The introduction of DEN-3 in central America in 1994 (after an absence of almost 20 years) 974 THE LANCET • Vol 352 • September 19. Samples positive for IgM antibody alone are thus not confirmatory for current infection. In interpreting laboratory results. a dipstick test. These kits do not require specialised training but their sensitivity and specificity are still being evaluated. neither Somalia nor Haiti have reported epidemic dengue in recent years. although frequent. With samples from the convalescent phase. the IgM ELISA is 90% sensitive but IgM antibody may be due to infection up to 3 months earlier. and the syndrome seems to occur at epidemic proportions only when the second infecting serotype is of south-east Asian origin. For a diagnosis of “confirmed” dengue. IgG antibody begins to appear by the fifth day after onset of symptoms.37. IgG antibody is generally already present in early acute serum samples and titres rise rapidly over a few days. or there should be a four-fold rise in antibody titre using a type-specific plaque reduction neutralisation test. only 289 (0·96%) developed a sustained fever over 38·3°C. it may transmit dengue by taking a blood meal.41 Travel What is the risk for travellers? Case-reports of dengue imported into non-endemic countries. 1998 . type and productivity of containers that hold larvae.51. Temperature.49 In over 20 000 troops in Haiti for six weeks in 1994. if necessary. 59 were diagnosed as dengue. Thus.42–44 The specific effect of other factors is much more difficult to judge. and insect repellent and bednets were not always used.SEMINAR format microtitre test. or by simply probing the skin of a susceptible person. In secondary (ie. This may overestimate the risk for tourists who will have less contact with the vector. it is important to consider the limitations of the tests. Other risk factors The risk for DHF is higher where two or more virus serotypes are circulating simultaneously. such as discarded tyres. and of these. Soldiers in the campaigns lived in austere locations. with most biting activity occurring in the early morning or late afternoon. 112 patients (about 0·1%) were evaluated for a temperature higher than 38·1°C without focal clinical findings. dengue virus should be identified by isolation. adult flight range. Moreover. and a rapid dot-blot test. staying a few days in air-conditioned hotels with well-kept grounds.32. Titres rise slowly for some weeks and then remain detectable for many years.39 Virus isolation from acute-phase samples requires a week of incubation and in most patients antibody will not be detectable earlier than 5 days after onset of symptoms. The risk of dengue for residents in an endemic area will vary with local conditions.40. buckets.54 Two cohort studies in Thailand found DHF Risk factors for infection and severe disease The reinfestation of a region with Ae aegypti or the introduction of a new serotype where the population’s immunity is low are clear harbingers of increased transmission. and other types of travel accommodation in locations with intense disease transmission have produced outbreaks with high attack rates.50 Travellers to dengue-endemic areas can reduce the probability of mosquito bites by wearing clothes that reduce the amount of exposed skin and using mosquito repellent and. wading pools. The species is day-active.38 The high rate of IgG positivity in people who have lived in the tropics makes analysis of paired acute and convalescent serum samples critical for such situations because the presence of IgG antibody in a single serum sample has no clinical significance. Laboratory confirmation of the diagnosis may be necessary for the patient’s medical record and for public-health surveillance but the high rate of false-negative results on acute sera means that serological tests should not be depended upon to guide management. if infection rather than clinical expression is measured. isolation of virus in tissue culture is 50% sensitive and the serology may be negative because of insufficient time for antibody development. IgG antibody is usually measured by the haemagglutination inhibition test or ELISA. and are reported only as “probable” dengue. and may approach 100% in outbreaks among susceptibles. This 1 per 1000 figure is only an average.51–53 The presence of circulating dengue antibodies. aerosol insecticides in rooms. human population density. repeat) infections. all interact in a manner that may prove different in risk analyses done in different outbreak investigations. immunohistochemistry in necropsy tissue. The adult mosquito usually rests in dark indoor sites such as closets and under beds. An estimate may be derived from three studies of non-tourists. virus strain. The mosquito becomes infected by a blood meal from a viraemic person and becomes infective after an obligatory extrinsic incubation period of 10–12 days. Healthcare providers should consider dengue in the differential diagnosis of all patients who have symptoms compatible with a systemic viral infection. produced widespread epidemics in 1995. negative results on acute-phase samples cannot exclude the diagnosis of dengue and convalescent samples should be taken. not more than 1% of 627 American residents in Bangkok in 1962–63 were infected with dengue or chikungunya viruses. more humid weather. do not allow an estimation of the risk of illness for the short-term traveller. and housing characteristics. and discarded coconut shells.
it is suggested. and aerosols targeted at adult mosquitoes and mostly applied outdoors as ultra-low volume (ULV) concentrates.68 Vector control At present dengue transmission can only be reduced by mosquito control.78. while accurate diagnosis and prompt treatment have a crucial role in the prevention of suffering and death due to dengue.52. most of all. government participation for the elimination of mosquito production sites when legal or large-scale action is necessary. that antibody-dependent enhancement has never been demonstrated in vivo in dengue-infected patients. and evaluated.62 A study in Cuba in 1981 found that DHF and DSS seemed to be more frequent in whites (than in blacks) and among those with a history of asthma.82. premembrane. through genetic manipulation.66.5.72 Great emphasis has been placed on defining the function of the water-holding container within the family’s daily activities.69 Not surprisingly. Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up. and sickle-cell anaemia63. Source (container) reduction campaigns have been very successful but they are hard to sustain. use of larvicides and adulticides. UK: CAB International.70. Kuno G.46. and its emergence in the Americas. This is regrettable. Virus replication induces infected monocytes to release vasoactive mediators. thus enhancing phagocytosis by mononuclear cells (the primary site of virus replication in man). Antibody-dependent enhancement of dengue viruses. World Health Stat Q 1997. and are plagued by diminishing returns. Clark GG. The task might seem a simple matter of the treatment or elimination of infested containers. acceptable to the family member “responsible” for the container type. safe and affordable vaccine is not an immediate prospect. Geneva: WHO. while promoting the involvement of anthropologists. 1: 55–57. because ULV aerosols have very limited impact on adult female Ae aegypti and no impact on the immature stages5. 2 3 4 5 THE LANCET • Vol 352 • September 19.76.17 Nevertheless. other risk factors for individual susceptibility to DHF have been suggested. and a project between the Government of Italy and the Pan American Health Organization in the Caribbean have focused on particular segments of the community. and safer. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem. Wallingford. The vast majority of these sites are present in the domestic environment as the result of human action. Vector control should be regarded in the same way as refuse disposal—a job that can never be finished.83 References 1 Gubler DJ. Corber SJ. Emphasis has shifted first to organochloride insecticides and later to organophosphorus larvicides. easy to perform and. there is no welldocumented example of interruption of a dengue epidemic by outdoor ULV treatments.5. though limited. be more immunogenic. may be made to replicate faster.71 Programmes sponsored by the Rotary Foundation and the Rockefeller Foundation. and some. These containers come in all shapes and sizes.60 DHF and DSS with fatalities have been documented in adults and children with primary dengue infection. Dengue and dengue hemorrhagic fever. undernourished infants seem to have a lower risk of DHF than infants with good nutritional status. and envelope genes of DEN 1. Gubler DJ. 50: 161–69. however.17 Indoor treatments are probably much more effective but are very labourintensive and intrusive. source reduction. The aerosols are principally recommended for emergency control during epidemic transmission as part of an integrated vector elimination effort. Epidemiological and laboratory evidence suggests that virus strain and perhaps serotype may also be important as a risk factor for DHF. Dengue/dengue hemorrhagic fever: the emergence of a global health problem. eds. treatment and control. and health communications specialists as members of the modern vector control team.5.10. mainly because they are labour intensive. 3. anything that will retain water in the tropics can be transformed into a developmental site for Ae aegypti.61 Although not well understood.5. Ironically. These recombinants.55 The most widely accepted hypothesis for the pathogenesis of DHF in secondary infections is immune enhancement.60.80 Laboratory-based surveillance is indispensable to guide recurrent and emergency interventions.SEMINAR rates of zero among children with primary infections and 1·8% and 12·5% among children with secondary infections. disseminated through the appropriate channels of communication. A cDNA infectious clone of the DEN-2 PDK-53 vaccine candidate virus has been constructed. an effective. attitudes and practices of community members about or toward the vector species and the disease. The promotion of community participation requires an understanding of the knowledge. and a tetravalent formulation is currently undergoing repeat phase I and II trials. In: Gubler DJ. and 4 into the DEN-2 PDK-53 backbone. Global situation of dengue and dengue haemorrhagic fever. Emerg Infect Dis 1995. Gubler DJ. including environmental management. Pinheiro FP. 1998 975 .59.17. diabetes. Candidate attenuated vaccine viruses have been evaluated in phase I and II trials in Thailand.64 epidemics has become widespread. therefore.71. and larvicides. require discipline and diligence.79 Effective and sustainable prevention of dengue outbreaks must include the individual community’s participation in dengue control.77 To be effective. their routine use as the principal response even before and after dengue Community participation In recent years there has been increased focus on the community’s role in Ae aegypti control. is a process in which the infecting virus is complexed with non-neutralising antibodies. 40: 571–78.81 When set against the large human and economic costs of recurrent dengue and DHF epidemics. 1986: 7–15. and work is in progress to construct chimaeric viruses by inserting the capsid. 1997: 1–22. economical.56–58 It should be pointed out. Prospects for control Vaccine development An effective vaccine will have to be tetravalent because pre-existing heterotypic dengue antibody is a risk factor for DHF. sociologists.67 However.65 Advances have also been made with second-generation recombinant dengue vaccines. Dengue haemorrhagic fever: diagnosis. prevention-oriented messages containing specific actions for specific mosquito production sites must be pretested. which result in the vascular permeability and haemorrhagic manifestations that characterise DHF and DSS.73–75 This information can then be discussed with the community members to define technical solutions that are effective. World Health Organization. the benefits of effective prevention are clear. Am J Trop Med Hyg 1989.
1962–64 I: observations on hospitalized patients with hemorrhagic fever. 46: 299–302. Hoke CH. Reed D. Dengue and dengue hemorrhagic fever. Thailand I: the 1980 outbreak. Nisalak A. Dupond J-L. 38 Chungue E. In: Gubler DJ. Wilkinson R. Viraemia in patients with naturally acquired dengue infection. Rojanasuphot S. Epidemiologic. interleukin-6 (IL-6). Indonesia. associated with low viremia in man. epidemiologic. Rojanasuphot S. 25: 1374–77. The clinical manifestations of dengue hemorrhagic fever in Puerto Rico. Hemsrichart V. Burke DS. Pathogenesis of dengue: challenges to molecular biology. The 1986 dengue and dengue hemorrhagic fever outbreak in Puerto Rico: epidemiologic and clinical observations. Nisalak A. 37: 434–54. Am J Trop Med Hyg 1976. Sumarmo. Roblin B. 49–58. Gubler DJ. Somalia. et al. Am J Trop Med Hyg 1984. 30: 1094–99. Dengue and dengue hemorrhagic fever. 1997: 313–33. Clinical and laboratory observations on patients with primary and secondary dengue type 1 infections with hemorrhagic manifestations in Fiji. Dengue and hemorrhagic fevers of southeast Asia. 57 Hober D. 42 CDC. 1998 . Lancet 1997. macrophages. 99: 291–96. Vázquez S. 39 Russell PK. MMWR 1995. 33: 158–65. Am J Trop Med Hyg 1988. Trofa AF. 20: 3–6. 77: 410–13. Scott TW. Ortiz S. Sukhavachana P. Suharyono W. 176: 313–21. et al. 61: 693–701. et al. Dengue and dengue hemorrhagic fever in the Americas: guidelines for prevention and control. UK: CAB International. 1990–91. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Gubler DJ. 53 Halstead SB. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. 9 (suppl) 59–64. 25: 146–50. Immunosuppression and cytotoxicity of dengue infection in the mouse model. Nisalak A. eds. Am J Epidemiol 1995. Rapid diagnosis and determination of duration of viraemia in dengue fever using a reverse transcriptase polymerase chain reaction. Diagnosis of dengue virus infections. 48: 324–31. Martínez Torres E. 40 Gubler DJ. Mosquito cell cultures and specific monocloal antibodies in surveillance for dengue viruses. J Med Assoc Thai 1994. Livingston PG. Suharyono W. Maryland Med J 1997. The effect of multiple host contacts on the infectivity of dengue-2 virus-infected Aedes aegypti. Dengue fever/dengue haemorrhagic fever: case management. Laferl H. Kuno G. 38: 411–19. Dengue infections with unusual manifestations. Am J Trop Med and Hyg 1958. Chye JK. Thisyakorn U. J Infect Dis 1997. UK: CAB International. Am J Trop Med Hyg 1988. Salitul V. Nisalak A. Vuitton DA. et al. de Wazières B. Hayes CG. Am J Trop Med Hyg 1992. In: Gubler DJ. 1992–1993. troops during Operation Restore Hope. Antibody. 15: 201–10. Am J Trop Med Hyg 1977. Rosen L. Bull WHO 1983. Nosocomial transmission of dengue from a needlestick injury. Vaughn DW. shock. Halstead S. Wulur H. 1997: 23–44. Sie A. 48 Halstead SB. In: Gubler DJ. P R Health Sci J 1996. Nimmannitya S. JC. 46 Newton EAC. Ussery MA. Wallingford. and hemorrhage: a pathogenic cascade. Am J Trop Med Hyg 1969. Immunopathologic mechanisms of dengue hemorrhagic fever and dengue shock syndrome. Margiotta MR. 16: 1034–42. Serum levels of tumor necrosis factor␣ (TNF␣). et al. Jatanasen S. Kalayanarooj S. Potential risk for dengue hemorrhagic fever: the isolation of serotype dengue-3 in Mexico. 131: 525–28. Prevots DR. Am J Trop Med Hyg 1989. Dengue in the early febrile phase: viremia and antibody responses. Antibody capture immunoassay detection of Japanese encephalitis virus immunoglobulin M and G antibodies in cerebrospinal fluid. double-blind study. and virologic observations on disease in non-indigenous white persons. 7: 561–77. Epidemic dengue 3 in central Java. Am J Trop Med Hyg 1995.S. Wallace MR. Pan Am J Public Health 1997. Davidson RN. 36 Innis BL. Kusalerdchariya S. Harun F. Bull WHO 1981. controlled trial. 36: 249–56. 277: 1546–48. Udomsakdi S. Dhiensiri T. Clinical observations on virologically confirmed fatal dengue infections in Jakarta. Emerg Inf Dis 1996. Virology 1997. Dengue and chikungunya virus infection in man in Thailand. 1: 193–99. Dengue type 3 infection—Nicaragua and Panama. A simulation model of the epidemiology of urban dengue fever: literature analysis. Vasanawathana S. Halstead SB. Rosen L. 351: 498. 41 Putnam JL. Yale J Biol Med 1965. et al. Sorensen K. Ahandrik S. 30: 545–51. Lanciotti RS. et al. Dengue encephalitis: a true entity? Am J Trop Med Hyg 1996. 35 Burke DS. Early clinical and laboratory indicators of acute dengue illness. 47: 709–20. 176: 322–30. Green S. Chirawatkul A. A plaque reduction test for dengue virus neutralizing antibodies. Arch Virol 1994. et al. Thisyakorn U. Suharyono W. 27: 581–89. Rigau-Pérez JG. Puerto Rico. model development. Poli L. Vaughn DW. Keesling JE. et al. Nimmannitya S. Gunarso S. Gubler DJ. Failure of carbazochrome sodium sulfonate (AC-17) to prevent dengue vascular permeability or shock: a randomized. Neurol J Southeast Asia 1996. Dengue fever: a risk to travelers. A model of the transmission of dengue fever with an evaluation of the impact of ultra-low volume (ULV) insecticide applications on dengue epidemics. et al. OctoberNovember 1994. Pleural effusion and ascites on return from Pakistan. J Immunol 1967. Jahja E. preliminary validation. 2: 133–35. 1: 381–88. Dengue y dengue hemorrágico: aspectos clínicos. Lam SK. Kuno G. 37 Clarke DH. Ref Inf Dis 1989. Argott-Ramírez E. Kuno G. A simple technique for demonstrating transmission of dengue virus by mosquitoes without the use of vertebrate hosts. and samples of simulation results. 120: 653–69. 59: 623–30. 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 976 THE LANCET • Vol 352 • September 19. Dengue in Nicaragua. Nisalak A. Pan Am J Public Health 1997. Chongswasdi V. Brown JL. 1990–1991. Nimmannitya S. 58 Kurane I. Nimmannitya S. 40: 418–27. dengue virus infection. Lim CT. Mukerjee R. George R. Lancet 1998. Pediatrics 1993. 47 Focks DA. George R. Am J Epidemiol 1984. Symptoms of dengue fever in relation to host immunologic response and virus serotype. et al. Casals J. 133: 1168–78. 69–70. Am J Epidemiol 1991. Salas RA. Harrison LM. Comparison of immunoglobulin G enzyme-linked immunosorbent assay (IgG-ELISA) and hemagglutination inhibition (HI) test for the detection of dengue antibodies: prevalence of dengue IgG-ELISA antibodies in Tahiti. 45 Koopman JS. 83: 708–71. Choy YS. Cobra C. Epidemiology of dengue and dengue hemorrhagic fever. 43 Guzmán MG. Clin Infect Dis 1997. and interleukin-1␤ (IL-1␤) in dengueinfected patients. 54: 256–59. Dengue in US military personnel in Haiti. UK: CAB International. Am J Trop Med Hyg 1995. Kuberski T. JAMA 1997. Southeast Asian J Trop Med Pub Hlth 1987. 56 Halstead SB. Vivona S. Phanthumachinda B. Washington. 1994: reintroduction of serotype 3 in the Americas. eds. 81: 170–74. Nimmannitya S. Thisyakorn C. Kuno G. 52 Rico-Hesse R. et al. Daniels E. Tassniyom S. 230: 244–51. Vorndam V. Kuno G. Chirawatkul A. 142: 1204–11. Eram S. Dengue haemorrhagic fever with unsual manifestations. Am J Trop Med Hyg 1981. Vertical transmission of dengue. Halstead SB. Tassniyom S. Johnson DE. et al. 239: 476–81. Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Ng KB. Risk factors in dengue shock syndrome: a prospective epidemiological study in Rayong. Wallingford. Vaca Marín MA. Reiter P. Pichart R. Marche G. Hitchcock Jr. 1997: 291–311. J Clin Microbiol 1992. Pan American Health Organization. Dengue fever in U. Puttisri P. Chaturvedi UC. and virologic observations on dengue in the Kingdom of Tonga. 51 Halstead SB. Science 1988. 38: 172–80. Sather GE. Vasanawathana S. 59 Gubler DJ. Rigau-Pérez JG and the Puerto Rico Association of Epidemiologists. 53: 89–94. Determinants and predictors of dengue infection in Mexico. Tan T. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled. 54: 489–506. Gubler DJ. Vorndam V. A prospective study of dengue infections in Bangkok. Dietz VJ. Rothman AL. Dengue infections with central nervous system manifestations. J Pediatr 1997. et al. Gómez-Dantés H. Trans R Soc Trop Med Hyg 1989. 49 Sharp TW. 55 Sangkawibha N. Nimmanitya S. Trop Med (Nagasaki) 1994. Lam SK. Calisher CH. 60 Gubler DJ. Nisalak A. 37 (suppl): 29–44. 1962–64 III: clinical. 350: 1072. Lubis I. et al. Haile DG. Trans R Soc Trop Med Hyg 1996. Dengue and dengue hemorrhagic fever. Singharaj P. et al. 18: 954–71. 18: 398–406. et al. 26: 775–83. Dhawan R. 92: 111–15. Salud Pública Mex 1995. Smoak BL. Dengue and chikungunya virus infection in man in Thailand. Rosen L. 44 Briseño-García B. Wallingford. 54 Kliks SC. Suntayakorn S.SEMINAR 6 Kalayanarooj S. 90: 140–43. Kuno G. Lam SK. J Parasitol 1995. Am J Trop Med Hyg 1993. DeFraites RF. Gubler DJ. 44: 21–24. J Infect Dis 1997. Gil H. Nisalak A. Am J Trop Med Hyg 1978. DC: PAHO Sci Publ no 548: 1994: 3–20. Martínez E. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. 11 (suppl 4): S830–39. Abidin M. 18: 984–96. Reed D. Lim JMH. Cohen SN. 50 Karp BE. J Clin Microbiol 1982. Viriyapongse S. et al. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. clinical. Lum LSC. Am J Trop Med Hyg 1969.
16: 295–97. Monath TP. 87: 267–71. UK: CAB International. Hitchens AP. Dengue and dengue hemorrhagic fever. Antibody-dependent enhancement of dengue-2 virus in people of white descent in Cuba. Disease control priorities in the developing countries. Wallingford. Heinz FX. Wallingford. Washington. Nimmanitya S. 81 Rigau-Pérez JG. 1997: 405–23. Gomez-Dantés H. 66 Kinney RM. Acta Trop 1994. Kinney RM. London: Cambridge University Press. Trans R Soc Trop Med Hyg 1993. Gubler DJ. Am J Trop Med Hyg 1976. Wallingford. etiology. The arboviruses: epidemiology and ecology. Pervokov Y. Acta Trop 1996. Clin Infect Dis 1993. Morens DM. FL: CRC Press. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. 1998 977 . Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting. Community involvement in control of Aedes aegypti. Aedes aegypti (L): the yellow fever mosquito: its life history. attitudes and practice in Trinidad and Tobago. Clark GG. Am J Trop Med Hyg 1994. Winch P. UK: CAB International 1997: 367–77. Philippine J Sci 1926. 29: 1–308. Gil E. Dengue and dengue hemorrhagic fever. Health Educ Res 1998. Gubler DJ. Why dengue haemorrhagic fever in Cuba? I: individual risk factors for fengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Chang GJ. Fields virology. The ethnoecology of dengue fever. Geneva: WHO. 76 Lloyd LS. Effect of a community-based Aedes aegypti control programme on mosquito larval production sites in El Progreso. Vector control at the household level: an analysis of its impact on women. epidemiology. Guzmán Tirado G. and prevention. 56: 327–39. In: Fields BN. 64 Morier L. 17: 321–35. 8: 107–28. Cultural factors in Aedes aegypti and dengue control in Latin America: a case study from the Dominican Republic. Vaccine 1997. et al. 94: 377–87. Med Anthropol Q 1997. Boca Raton. Ragoonanansingh R. Dengue: a worldwide problem. UK: CAB International. 230: 300–08. Leontsini E. Kendall C. eds. Reiter P. 1997: 425–62. Rojas Z. Kendall C. vol II: 223–60. Flaviviruses. Int Quart Community Hlth Educ 1990. 19: 500–12. 1997: 379–403. Hoemeke L. Infect Dis Clin N Am 1994. a common strategy (Proceedings of International Conference on Dengue and Aedes aegypti Community-based Control). 79 Leontsini E. 1992. Philadelphia: Lippincott-Raven. Bancroft WH. World Health Organization. 72 Rosenbaum J. Kuno G. Laboratory Halstead SB. Dengue haemorrhagic fever: diagnosis. Ramírez-Ronda CH. 3: 399–419. Laboratory Monath TP. Yoksan S. J Trop Med Hyg 1991. Virology 1997. Surveillance for dengue and dengue hemorrhagic fever. Using disability-adjusts life years to assess the economic impact of dengue in Puerto Rico: 1984–1994. Kourí GP. THE LANCET • Vol 352 • September 19. eds. 82 Halstead SB. Shock syndrome in primary dengue infections. ed. 74 Winch P. In: Monath TP. Dengue and dengue hemorrhagic fever. 63 Bravo JR. In: Gubler DJ. Kuno G. In: Jamison DT. Dengue (with notes on yellow fever and Japanese encephalitis). Kendall C. Ortega-Canto J. 25: 866–74. eds. Clark GG. Soler-Nodarse M. The politics of malaria vector control. i: 1028–29. et al. Dengue and dengue hemorrhagic fever. 1994. 73 Gordon AJ. 80 Schofield CJ. 77 Winch P. Lloyd LS. clinical manifestations. Epidemiol Rev 1995. bionomics. 11: 202–23. 70 Gubler DJ. Surveillance and control of urban dengue vectors. Pan American Health Organization. 1986.SEMINAR 61 Scott RMcN. 83 Meltzer MI. In: Gubler DJ. eds. Nimmanitya S. Rigau-Pérez JG. Health Policy Planning 1992. 69 Reiter P. Clinical Manifestations Siler JF. 65 Bhamarapravati N. Community participation in dengue prevention and control: a survey of knowledge. treatment and control. 1997. 1960. eds. Am J Trop Med Hyg 1994. Nathan MB. García CD. 50 (suppl 6): 50–60. Am J Trop Med Hyg 1998. Tidwell M. Further reading Transmission Christophers SR. immunity. Hall MW. and structure. Kuno G. 1988. 15: 1494–502. 1996: 961–1034. In: Gubler DJ. Gubler DJ. Risk factors Kuno G. Lloyd L. Beliefs about the prevention of dengue and other febrile illnesses in Merida. Clark GG. In: Gubler DJ. Kendall C. General Gubler DJ. eds. Kuno G. ed. Mexico. 10: 193–211. The design of a community-based health education intervention for the control of Aedes aegypti. Am J Trop Med Hyg 1995. Knipe DM. 53: 111–17. 81: 816–20. 7: 342–51. et al. UK: CAB International. 78 Gordon AJ. DC: PAHO Sci Publ no 548. Shepard DS. Butrapet S. Live attenuated tetravalent dengue vaccine. Lancet 1987. Community-based integrated control of Aedes aegypti: a brief overview of current programs. 59: 265–71. New York: Oxford University Press. Godas MD. Dengue. 62 Thisyakorn U. Trans Royal Soc Trop Med Hyg 1987. Wallingford. Review of the factors modulating dengue transmission. Kuno G. Construction of infectious cDNA for dengue 2 virus: strain 16681 and its attenuated vaccine derivative. Clin Inf Dis 1994. 67 Trent DW. Dengue and dengue hemorrhagic fever. Dengue: its history. Wallingford. Clark GG. 61: 169–79. 68 Chambers TJ. Mexico City: Ministry of Health/Rockefeller Foundation. Gubler DJ. 71 Winch P. International. Honduras. 83: 1–4. UK: CAB International. et al. 1993: 303–20. Gubler DJ. Howley PM. Effectiveness of community participation in vector-borne disease control. Nutritional status of children with dengue hemorrhagic fever. Dengue and dengue hemorrhagic fever in the Americas: guidelines for prevention and control. 50: 401–11. 75 Whiteford LM. Kouri-Flores G.mechanisms of transmission. Recombinant dengue virus vaccines. Mixed strategies in health education and community participation: an evaluation of dengue control in the Dominican Republic. Dengue in the western hemisphere. Huang CY-H. strain PDK-53. Guzmán MG. Tsai TF. Gubler DJ. Bull Ent Res 1993.
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