Announcement

Collapse
No announcement yet.

Dengue and dengue haemorrhagic fever

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • Dengue and dengue haemorrhagic fever

    The Lancet 1998; 352:971-977
    DOI:10.1016/S0140-6736(97)12483-7
    Dengue and dengue haemorrhagic fever

    Dr Jos? G Rigau-P?rez a , Gary G ClarkPhD a, Duane J GublerScD b, Paul ReiterDPhil a, Eduard J SandersMD a and A Vance VorndamPhD a

    Summary
    Epidemiology
    Clinical manifestations
    Treatment
    Laboratory diagnosis
    Disease transmission
    Risk factors for infection and severe disease
    Prospects for control
    References

    Summary

    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.
    Back to top


    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.


    Click to enlarge image


    Figure 1. World distribution of dengue


    Epidemiology

    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 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
    Back to top

    Clinical manifestations

    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 infections.7,10?12 Infants and young children may have an undifferentiated febrile disease with a maculopapular rash. Older children and adults may have either a mild febrile syndrome or the classical and even incapacitating disease. Skin eruptions are reported in over 50% of laboratory-confirmed dengue cases in Puerto Rico, more commonly in children and adults with primary infections.7 There may be a flushing of the face, neck, and chest initially in the febrile period; or a centrifugal maculopapular rash arising on the third or fourth day; or a later confluent petechial rash with round pale areas of normal skin; or a combination of these manifestations.13,14
    Leukopenia and mild thrombocytopenia are frequent.6,13 Less frequent, but not rare, are haemorrhagic manifestations such as petechiae, epistaxis, gingival bleeding, gastrointestinal bleeding, microscopic haematuria, and hypermenorrhoea.7,14 A positive tourniquet test (more than 20 petechiae in a square patch of skin 2?5?2?5 cm [>20/in2]) may be found in over one-third of patients with DF.6 Clinical findings alone are not very helpful to distinguish DF from other febrile illnesses such as the chikungunya, measles, leptospirosis, typhoid, or malaria.13,15 If symptoms start more than two weeks after the patient has left a dengue-endemic area, or if the fever lasts more than two weeks, dengue can be effectively ruled out.

    Dengue haemorrhagic fever

    DHF has been most extensively studied in south-east Asia, where it first appeared and where it is primarily a children's disease.15,16 In the tropical Americas it is seen in all age groups, and the basic clinical manifestations are similar throughout the age spectrum.12,17,18 DHF is defined as an acute febrile illness with minor or major bleeding, thrombocytopenia (≤105/μL), 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), pleural or other effusions, or hypoalbuminaemia or hypoproteinaemia.17 The major pathophysiological change that determines the severity of disease in DHF and differentiates it from DF is the leakage of plasma. Extravasation occurs through endothelial gaps, without necrosis or inflammation of the capillary endothelium.19 Nevertheless, a recent clinical trial showed that a drug that counteracts capillary permeability induced by histamine or hyaluronidase, and is currently marketed in Asia (carbazochrome sodium sulphonate) did not prevent dengue vascular permeability or shock.20
    DHF commonly begins with a sudden rise in temperature and other symptoms resembling DF. The temperature is typically high (38?40?C) and continues for 2?7 days. DHF and dengue shock usually develop around the third to seventh day of illness.4 The most common haemorrhagic feature is a positive tourniquet test (over 50% of patients).6 Petechiae, easily bruised skin, and subcutaneous bleeding at venepuncture sites are present in most cases.14 Transudate due to excessive capillary permeability collects at the pleural and abdominal cavities. 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%.6 The development of DHF provides warnings of an increased probability of shock (figure 2). The first (and easiest information) to ascertain is the time elapsed since onset of illness. DHF/DSS usually develop around day 3?7 of illness, at the time of defervescence, which is an indication for intensified observation.4,17 A progressively decreasing platelet count and a rising haematocrit (signalling abnormal capillary permeability) indicate increased probability of impending shock.14 When all four criteria for DHF are fulfilled, intravenous fluids (see below) may be all that is required for treatment. 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.


    Click to enlarge image


    Figure 2. Warning signs for dengue shock



    Dengue shock syndrome

    DSS is defined as DHF with signs of circulatory failure, including narrow pulse pressure (≤20 mm Hg), hypotension, or frank shock. The liver may be palpable and tender; and liver enzymes are usually mildly abnormal but jaundice is rare.6,21 The four warning signs for impending shock are intense, sustained abdominal pain; persistent vomiting; restlessness or lethargy; and a sudden change from fever to hypothermia with sweating and prostration. The development of any of these signs or any suggestion of hypotension are indications for hospital admission and management to prevent shock.18 The patient may recover rapidly after volume replacement but shock may recur during the period of excessive capillary permeability. The prognosis in DHF/DSS depends on prevention or early recognition and treatment of shock. In hospitals with long experience of DSS the case fatality rate in DHF can be as low as 0?2%. Once shock has set in the fatality rate may be high (12% to 44%).14,22

    Other severe dengue syndromes

    There are some unusual but well-described manifestations of dengue infection where the risk of death is high. These are DF with severe haemorrhage, hepatic damage, cardiomyopathy, and encephalopathy.14,23,24 Neurological manifestations such as altered consciousness, convulsions, and coma have been ascribed to an encephalopathy secondary to prolonged DHF/DSS, resulting from the leakage of plasma into serous spaces, haemorrhage, shock, and metabolic disturbances.23,25,26 However, invasion of the central nervous system (viral encephalitis) is a recently documented possibility.27
    Vertical transmission of dengue virus has been recorded in a small number of cases, leading to neonatal DF or even DSS.28 One case of nosocomial transmission from a needlestick injury has been reported.29
    Back to top


    Treatment

    Patients with DF require rest, oral fluids to compensate for losses via diarrhoea or vomiting, analgesics, and antipyretics for high fever (paracetamol [acetaminophen] but not aspirin, so that platelet function will not be impaired). Steroids in DSS are not helpful.22 With the earliest suspicion of threatened severe illness, an intravenous line should be placed so that fluids can be provided. Monitoring of blood pressure, haematocrit, platelet count, haemorrhagic manifestations, urinary output, and level of consciousness is important. Plasma leakage in DHF is very rapid and the haematocrit may continue to rise even while intravenous fluids are being administered; however, the ?leaky capillary? period is short and intravenous fluids are usually required for only 1?2 days.4,14,17,18 There is great variability from patient to patient, and the physician must adjust treatment using serial haematocrit, blood pressure, and urinary output data.14,30 Insufficient volume replacement will allow worsening shock, acidosis, and disseminated intravasular coagulation, while fluid overload will produce massive effusions, respiratory compromise, and congestive heart failure. Because patients have loss of plasma (through increased vascular permeability into the serous spaces) they must be given isotonic solutions and plasma expanders, such as Ringer's acetate or Ringer's lactate, plasma protein fraction, and dextran 40. The recommended amount of total fluid replacement in 24 h is approximately the volume required for maintenance, plus replacement of 5% of bodyweight deficit, but this volume is not administered uniformly throughout the 24 h. A bolus of 10?20 mL of an isotonic solution per kg bodyweight is given in case of shock, and repeated every 30 min until circulation improves and urinary output is adequate. Vital signs should be measured every 30?60 min and haematocrit every 2?4 h, then less frequently as the patient's condition stabilises.4,14,17,18
    Placement of a central-venous-pressure line is hazardous in patients with haemorrhagic tendencies but may be necesssary, especially when more than 60 mL/kg of fluids has been given without improvement. The line should be inserted by an expert in a special care area. It is used to estimate filling pressures and to guide further intravenous fluid administration. An arterial line will help in the assessment of arterial blood gases, acid-base status, coagulation profiles, and electrolytes in the haemodynamically unstable patient, helping to identify early respiratory compromise.
    Monitoring should be continued for at least a day after defervescence. Once the patient begins to recover, extravasated fluid is rapidly resabsorbed, causing a drop in haematocrit. Before discharge, the patient should meet the following criteria: absence of fever for 24 h (without antipyretics) and a return of appetite; improvement in the clinical picture; hospital care for at least 3 days after recovery from shock; no respiratory distress from pleural effusion or ascites; stable haematocrit; and platelet count greater than 50 000/μL.17 Because convalescent-phase diagnostic samples are often difficult to obtain, a second blood sample should always be taken on the day of discharge.
    Back to top

    Laboratory diagnosis

    Dengue viruses belong to the Flaviviridae, a family which contains almost 70 viruses, including those causing yellow fever and several encephalitides (eg, Japanese, St Louis, West Nile, and tick-borne). All these flaviviruses share group antigens that can cross-react in serological tests, complicating diagnosis. Serum is the specimen of choice for both virological and serological studies. Circulating virus remains detectable in the blood during the febrile period (for an average of 5 days after onset of symptoms), and is then rapidly cleared with the appearance of specific antibody. The virus is stable in diagnostic samples up to 5 days at 4?C. If longer storage is needed, the sample should be frozen at 60?C or lower. Most laboratories attempting virus isolation utilise an established cell culture line of Ae albopictus cells. After a week of incubation, the cells are stained with fluorescein-conjugated polyclonal antibodies to detect virus isolates, which are then serotyped with monoclonal antibodies in an indirect fluorescent antibody test.31 Use of the polymerase chain reaction (PCR) may shorten the time required for result. PCR can also detect viruses inactivated by improper storage or by complexing with neutralising antibody.32?34 However, the PCR test is experimental and no commercial products are available.
    Serological diagnosis depends on the presence of IgM antibody or a rise in IgG antibody titre in paired acute and convalescent phase sera. 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. This antibody may be detectable for a median of about 60 days. Currently, the most widely used IgM assay is a capture ELISA (enzyme-linked immunosorbent assay).35 Where two flaviviruses cocirculate, such as dengue and Japanese encephalitis in Asia, a differential diagnosis can be made by measurement of antibody titres against these antigens separately,36 but this technique cannot reliably differentiate among the four dengue serotypes. Commercial kits for the measurement of antibodies to dengue viruses include the standard ELISA-format microtitre test, a dipstick test, and a rapid dot-blot test. These kits do not require specialised training but their sensitivity and specificity are still being evaluated.
    In primary dengue, IgG antibody begins to appear by the fifth day after onset of symptoms. Titres rise slowly for some weeks and then remain detectable for many years. In secondary (ie, repeat) infections, IgG antibody is generally already present in early acute serum samples and titres rise rapidly over a few days. IgG antibody is usually measured by the haemagglutination inhibition test or ELISA.37,38 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.
    In interpreting laboratory results, it is important to consider the limitations of the tests. With acute-phase samples, isolation of virus in tissue culture is 50% sensitive and the serology may be negative because of insufficient time for antibody development. Thus, negative results on acute-phase samples cannot exclude the diagnosis of dengue and convalescent samples should be taken. 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. Moreover, the ELISA cross-reacts with other flaviviruses. Samples positive for IgM antibody alone are thus not confirmatory for current infection, and are reported only as ?probable? dengue. For a diagnosis of ?confirmed? dengue, dengue virus should be identified by isolation, immunohistochemistry in necropsy tissue, or there should be a four-fold rise in antibody titre using a type-specific plaque reduction neutralisation test.32,39 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. 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.
    Back to top

    Disease transmission

    Ae aegypti is closely associated with human habitation. Larvae are mostly found in artificial containers that may hold water, such as discarded tyres, buckets, flowerpots, wading pools, and blocked rain gutters, but they can also be found in natural sites such as bromeliads, treeholes, and discarded coconut shells. The adult mosquito usually rests in dark indoor sites such as closets and under beds. The species is day-active, with most biting activity occurring in the early morning or late afternoon. 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. After the mosquito becomes infective, it may transmit dengue by taking a blood meal, or by simply probing the skin of a susceptible person.40,41
    Back to top

    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. The introduction of DEN-3 in central America in 1994 (after an absence of almost 20 years) produced widespread epidemics in 1995.42?44 The specific effect of other factors is much more difficult to judge. Dengue incidence fluctuates with the seasons and is usually associated with warmer, more humid weather. Temperature, humidity, mosquito population densities and survival, type and productivity of containers that hold larvae, adult flight range, human population density, virus strain, immunity for specific virus serotypes, human behaviour, and housing characteristics, all interact in a manner that may prove different in risk analyses done in different outbreak investigations. The risk of dengue for residents in an endemic area will vary with local conditions, and may approach 100% in outbreaks among susceptibles, if infection rather than clinical expression is measured. Several mathematical models have recently explored the interactions of multiple factors that give rise to epidemic transmission in a community.45?47
    Travel

    What is the risk for travellers? Case-reports of dengue imported into non-endemic countries, although frequent, do not allow an estimation of the risk of illness for the short-term traveller. An estimate may be derived from three studies of non-tourists. Despite high concurrent infection rates in Thais, not more than 1% of 627 American residents in Bangkok in 1962?63 were infected with dengue or chikungunya viruses.48 In over 30 000 United States troops in Somalia for three months (1993?94), only 289 (0?96%) developed a sustained fever over 38?3?C, and of these, 59 were diagnosed as dengue.49 In over 20 000 troops in Haiti for six weeks in 1994, 112 patients (about 0?1%) were evaluated for a temperature higher than 38?1?C without focal clinical findings, and only 30 had confirmed dengue.13 Although we have no data on the dengue incidence rate in the local populations, neither Somalia nor Haiti have reported epidemic dengue in recent years. Soldiers in the campaigns lived in austere locations, exposure to mosquitoes was common, and insect repellent and bednets were not always used.
    These data allow for an estimate of roughly 1 illness per 1000 travellers. This may overestimate the risk for tourists who will have less contact with the vector, staying a few days in air-conditioned hotels with well-kept grounds. This 1 per 1000 figure is only an average, 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, if necessary, aerosol insecticides in rooms. Healthcare providers should consider dengue in the differential diagnosis of all patients who have symptoms compatible with a systemic viral infection, and who reside in or have recently visited tropical areas.

    Other risk factors

    The risk for DHF is higher where two or more virus serotypes are circulating simultaneously, and the syndrome seems to occur at epidemic proportions only when the second infecting serotype is of south-east Asian origin.51?53 The presence of circulating dengue antibodies, 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.51,54 Two cohort studies in Thailand found DHF rates of zero among children with primary infections and 1?8% and 12?5% among children with secondary infections.10,55 The most widely accepted hypothesis for the pathogenesis of DHF in secondary infections is immune enhancement. Antibody-dependent enhancement of dengue viruses, it is suggested, is a process in which the infecting virus is complexed with non-neutralising antibodies, thus enhancing phagocytosis by mononuclear cells (the primary site of virus replication in man). Virus replication induces infected monocytes to release vasoactive mediators, which result in the vascular permeability and haemorrhagic manifestations that characterise DHF and DSS.56?58 It should be pointed out, however, that antibody-dependent enhancement has never been demonstrated in vivo in dengue-infected patients.
    Epidemiological and laboratory evidence suggests that virus strain and perhaps serotype may also be important as a risk factor for DHF.52,59,60 DHF and DSS with fatalities have been documented in adults and children with primary dengue infection.60,61 Although not well understood, other risk factors for individual susceptibility to DHF have been suggested. Ironically, undernourished infants seem to have a lower risk of DHF than infants with good nutritional status.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, diabetes, and sickle-cell anaemia63,64
    Back to top


    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. Candidate attenuated vaccine viruses have been evaluated in phase I and II trials in Thailand, and a tetravalent formulation is currently undergoing repeat phase I and II trials.65 Advances have also been made with second-generation recombinant dengue vaccines. A cDNA infectious clone of the DEN-2 PDK-53 vaccine candidate virus has been constructed, and work is in progress to construct chimaeric viruses by inserting the capsid, premembrane, and envelope genes of DEN 1, 3, and 4 into the DEN-2 PDK-53 backbone. These recombinants, through genetic manipulation, may be made to replicate faster, be more immunogenic, and safer.66,67 However, an effective, safe and affordable vaccine is not an immediate prospect.68

    Vector control

    At present dengue transmission can only be reduced by mosquito control. The task might seem a simple matter of the treatment or elimination of infested containers. Source (container) reduction campaigns have been very successful but they are hard to sustain, mainly because they are labour intensive, require discipline and diligence, and are plagued by diminishing returns. Emphasis has shifted first to organochloride insecticides and later to organophosphorus larvicides, and aerosols targeted at adult mosquitoes and mostly applied outdoors as ultra-low volume (ULV) concentrates. The aerosols are principally recommended for emergency control during epidemic transmission as part of an integrated vector elimination effort, including environmental management, source reduction, and larvicides.17 Nevertheless, their routine use as the principal response even before and after dengue epidemics has become widespread. This is regrettable, because ULV aerosols have very limited impact on adult female Ae aegypti and no impact on the immature stages5,46,69 Not surprisingly, therefore, there is no well-documented example of interruption of a dengue epidemic by outdoor ULV treatments.17 Indoor treatments are probably much more effective but are very labourintensive and intrusive.

    Community participation

    In recent years there has been increased focus on the community's role in Ae aegypti control.5,17,70,71 Programmes sponsored by the Rotary Foundation and the Rockefeller Foundation, 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, while promoting the involvement of anthropologists, sociologists, and health communications specialists as members of the modern vector control team.5,72 Great emphasis has been placed on defining the function of the water-holding container within the family's daily activities. These containers come in all shapes and sizes; anything that will retain water in the tropics can be transformed into a developmental site for Ae aegypti. The vast majority of these sites are present in the domestic environment as the result of human action. The promotion of community participation requires an understanding of the knowledge, attitudes and practices of community members about or toward the vector species and the disease.5,71,73?75 This information can then be discussed with the community members to define technical solutions that are effective, economical, easy to perform and, most of all, acceptable to the family member ?responsible? for the container type.76,77 To be effective, prevention-oriented messages containing specific actions for specific mosquito production sites must be pretested, disseminated through the appropriate channels of communication, and evaluated.78,79
    Effective and sustainable prevention of dengue outbreaks must include the individual community's participation in dengue control; government participation for the elimination of mosquito production sites when legal or large-scale action is necessary; and some, though limited, use of larvicides and adulticides. Vector control should be regarded in the same way as refuse disposal?a job that can never be finished.80 Laboratory-based surveillance is indispensable to guide recurrent and emergency interventions, while accurate diagnosis and prompt treatment have a crucial role in the prevention of suffering and death due to dengue.81 When set against the large human and economic costs of recurrent dengue and DHF epidemics, the benefits of effective prevention are clear.5,82,83
    Back to top




    <!--start tail=-->References

    1. Gubler DJ. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 1-22.
    2. Gubler DJ, Clark GG. Dengue/dengue hemorrhagic fever: the emergence of a global health problem. Emerg Infect Dis 1995; 1: 55-57. MEDLINE
    3. Pinheiro FP, Corber SJ. Global situation of dengue and dengue haemorrhagic fever, and its emergence in the Americas. World Health Stat Q 1997; 50: 161-169.
    4. World Health Organization. In: Dengue haemorrhagic fever: diagnosis, treatment and control. Geneva: WHO, 1986: 7-15.
    5. Gubler DJ. Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up. Am J Trop Med Hyg 1989; 40: 571-578. MEDLINE
    6. Kalayanarooj S, Vaughn DW, Nimmannitya S, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176: 313-321.
    7. Cobra C, Rigau-P?rez JG, Kuno G, Vorndam V. Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990?1991. Am J Epidemiol 1995; 142: 1204-1211. MEDLINE
    8. Gubler DJ, Suharyono W, Tan T, Abidin M, Sie A. Viraemia in patients with naturally acquired dengue infection. Bull WHO 1981; 59: 623-630. MEDLINE
    9. Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis 1997; 176: 322-330.
    10. Burke DS, Nisalak A, Johnson DE, et al. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 1988; 38: 172-180. MEDLINE
    11. Kuberski T, Rosen L, Reed D, et al. Clinical and laboratory observations on patients with primary and secondary dengue type 1 infections with hemorrhagic manifestations in Fiji. Am J Trop Med Hyg 1977; 26: 775-783. MEDLINE
    12. Dietz VJ, Gubler DJ, Ortiz S, et al. The 1986 dengue and dengue hemorrhagic fever outbreak in Puerto Rico: epidemiologic and clinical observations. P R Health Sci J 1996; 15: 201-210.
    13. Trofa AF, DeFraites RF, Smoak BL, et al. Dengue in US military personnel in Haiti. JAMA 1997; 277: 1546-1548.
    14. Nimmannitya S. Dengue fever/dengue haemorrhagic fever: case management. Trop Med (Nagasaki) 1994; 36: 249-256.
    15. Halstead SB. Dengue and hemorrhagic fevers of southeast Asia. Yale J Biol Med 1965; 37: 434-454. MEDLINE
    16. Nimmannitya S, Halstead SB, Cohen SN, Margiotta MR. Dengue and chikungunya virus infection in man in Thailand, 1962?64 I: observations on hospitalized patients with hemorrhagic fever. Am J Trop Med Hyg 1969; 18: 954-971. MEDLINE
    17. Pan American Health Organization. Dengue and dengue hemorrhagic fever in the Americas: guidelines for prevention and control. Washington, DC. PAHO Sci Publ 1994; (no 548): 3-2049?58, 69?70..
    18. Mart?nez Torres E. Dengue y dengue hemorr?gico: aspectos cl?nicos. Salud P?blica Mex 1995; 37 (suppl): 29-44.
    19. Chaturvedi UC, Dhawan R, Mukerjee R. Immunosuppression and cytotoxicity of dengue infection in the mouse model In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 291-311.
    20. Tassniyom S, Vasanawathana S, Dhiensiri T, Nisalak A, Chirawatkul A. Failure of carbazochrome sodium sulfonate (AC-17) to prevent dengue vascular permeability or shock: a randomized, controlled trial. J Pediatr 1997; 131: 525-528. Abstract | Full Text | PDF (1341 KB) | CrossRef
    21. Rigau-P?rez JG. Puerto Rico Association of Epidemiologists. The clinical manifestations of dengue hemorrhagic fever in Puerto Rico, 1990?91. Pan Am J Public Health 1997; 1: 381-388.
    22. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Pediatrics 1993; 92: 111-115. MEDLINE
    23. Sumarmo, Wulur H, Jahja E, Gubler DJ, Suharyono W, Sorensen K. Clinical observations on virologically confirmed fatal dengue infections in Jakarta, Indonesia. Bull WHO 1983; 61: 693-701. MEDLINE
    24. Nimmannitya S, Thisyakorn U, Hemsrichart V. Dengue haemorrhagic fever with unsual manifestations. Southeast Asian J Trop Med Pub Hlth 1987; 18: 398-406.
    25. Thisyakorn U, Thisyakorn C. Dengue infections with unusual manifestations. J Med Assoc Thai 1994; 77: 410-413. MEDLINE
    26. Lam SK. Dengue infections with central nervous system manifestations. Neurol J Southeast Asia 1996; 20: 3-6.
    27. Lum LSC, Lam SK, Choy YS, George R, Harun F. Dengue encephalitis: a true entity?. Am J Trop Med Hyg 1996; 54: 256-259. MEDLINE
    28. Chye JK, Lim CT, Ng KB, Lim JMH, George R, Lam SK. Vertical transmission of dengue. Clin Infect Dis 1997; 25: 1374-1377.
    29. de Wazi?res B, Gil H, Vuitton DA, Dupond J-L. Nosocomial transmission of dengue from a needlestick injury. Lancet 1998; 351: 498. Full Text | PDF (56 KB) | CrossRef
    30. Laferl H. Pleural effusion and ascites on return from Pakistan. Lancet 1997; 350: 1072. Full Text | PDF (310 KB) | CrossRef
    31. Gubler DJ, Kuno G, Sather GE, et al. Mosquito cell cultures and specific monocloal antibodies in surveillance for dengue viruses. Am J Trop Med Hyg 1984; 33: 158-165. MEDLINE
    32. Vorndam V, Kuno G. Diagnosis of dengue virus infections In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 313-333.
    33. Lanciotti RS, Calisher CH, Gubler DJ, et al. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 1992; 30: 545-551. MEDLINE
    34. Brown JL, Wilkinson R, Davidson RN, et al. Rapid diagnosis and determination of duration of viraemia in dengue fever using a reverse transcriptase polymerase chain reaction. Trans R Soc Trop Med Hyg 1996; 90: 140-143. MEDLINE | CrossRef
    35. Burke DS, Nisalak A, Ussery MA. Antibody capture immunoassay detection of Japanese encephalitis virus immunoglobulin M and G antibodies in cerebrospinal fluid. J Clin Microbiol 1982; 16: 1034-1042. MEDLINE
    36. Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 1989; 40: 418-427. MEDLINE
    37. Clarke DH, Casals J. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. Am J Trop Med and Hyg 1958; 7: 561-577.
    38. Chungue E, Marche G, Pichart R, et al. 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. Trans R Soc Trop Med Hyg 1989; 83: 708-771. MEDLINE | CrossRef
    39. Russell PK, Nisalak A, Sukhavachana P, Vivona S. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol 1967; 99: 291-296. MEDLINE
    40. Gubler DJ, Rosen L. A simple technique for demonstrating transmission of dengue virus by mosquitoes without the use of vertebrate hosts. Am J Trop Med Hyg 1976; 25: 146-150. MEDLINE
    41. Putnam JL, Scott TW. The effect of multiple host contacts on the infectivity of dengue-2 virus-infected Aedes aegypti. J Parasitol 1995; 81: 170-174. MEDLINE | CrossRef
    42. CDC. Dengue type 3 infection?Nicaragua and Panama, October-November 1994. MMWR 1995; 44: 21-24.
    43. Guzm?n MG, V?zquez S, Mart?nez E, et al. Dengue in Nicaragua, 1994: reintroduction of serotype 3 in the Americas. Pan Am J Public Health 1997; 1: 193-199.
    44. Brise?o-Garc?a B, G?mez-Dant?s H, Argott-Ram?rez E, et al. Potential risk for dengue hemorrhagic fever: the isolation of serotype dengue-3 in Mexico. Emerg Inf Dis 1996; 2: 133-135.
    45. Koopman JS, Prevots DR, Vaca Mar?n MA, et al. Determinants and predictors of dengue infection in Mexico. Am J Epidemiol 1991; 133: 1168-1178. MEDLINE
    46. Newton EAC, Reiter P. A model of the transmission of dengue fever with an evaluation of the impact of ultra-low volume (ULV) insecticide applications on dengue epidemics. Am J Trop Med Hyg 1992; 47: 709-720. MEDLINE
    47. Focks DA, Daniels E, Haile DG, Keesling JE. A simulation model of the epidemiology of urban dengue fever: literature analysis, model development, preliminary validation, and samples of simulation results. Am J Trop Med Hyg 1995; 54: 489-506.
    48. Halstead SB, Udomsakdi S, Singharaj P, Nisalak A. Dengue and chikungunya virus infection in man in Thailand, 1962?64 III: clinical, epidemiologic, and virologic observations on disease in non-indigenous white persons. Am J Trop Med Hyg 1969; 18: 984-996. MEDLINE
    49. Sharp TW, Wallace MR, Hayes CG, et al. Dengue fever in U.S. troops during Operation Restore Hope, Somalia, 1992?1993. Am J Trop Med Hyg 1995; 53: 89-94. MEDLINE
    50. Karp BE. Dengue fever: a risk to travelers. Maryland Med J 1997; 46: 299-302.
    51. Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988; 239: 476-481. MEDLINE
    52. Rico-Hesse R, Harrison LM, Salas RA, et al. Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology 1997; 230: 244-251. CrossRef
    53. Halstead SB. Epidemiology of dengue and dengue hemorrhagic fever In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 23-44.
    54. Kliks SC, Nimmanitya S, Nisalak A, et al. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 1988; 38: 411-419. MEDLINE
    55. Sangkawibha N, Rojanasuphot S, Ahandrik S, Viriyapongse S, Jatanasen S, Salitul V, Phanthumachinda B, Halstead S. Risk factors in dengue shock syndrome: a prospective epidemiological study in Rayong, Thailand I: the 1980 outbreak. Am J Epidemiol 1984; 120: 653-669. MEDLINE
    56. Halstead SB. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: a pathogenic cascade. Ref Inf Dis 1989; 11 (suppl 4): S830-S839.
    57. Hober D, Poli L, Roblin B, et al. Serum levels of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in dengue-infected patients. Am J Trop Med Hyg 1993; 48: 324-331. MEDLINE
    58. Kurane I, Rothman AL, Livingston PG, et al. Immunopathologic mechanisms of dengue hemorrhagic fever and dengue shock syndrome. Arch Virol 1994; 9 (suppl): 59-64.
    59. Gubler DJ, Reed D, Rosen L, Hitchcock JC Jr. Epidemiologic, clinical, and virologic observations on dengue in the Kingdom of Tonga. Am J Trop Med Hyg 1978; 27: 581-589. MEDLINE
    60. Gubler DJ, Suharyono W, Lubis I, Eram S, Gunarso S. Epidemic dengue 3 in central Java, associated with low viremia in man. Am J Trop Med Hyg 1981; 30: 1094-1099. MEDLINE
    61. Scott RMcN, Nimmanitya S, Bancroft WH, et al. Shock syndrome in primary dengue infections. Am J Trop Med Hyg 1976; 25: 866-874. MEDLINE
    62. Thisyakorn U, Nimmanitya S. Nutritional status of children with dengue hemorrhagic fever. Clin Infect Dis 1993; 16: 295-297. MEDLINE
    63. Bravo JR, Guzm?n MG, Kour? GP. Why dengue haemorrhagic fever in Cuba? I: individual risk factors for fengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Trans Royal Soc Trop Med Hyg 1987; 81: 816-820.
    64. Morier L, Kouri-Flores G, Guzm?n Tirado G, Soler-Nodarse M. Antibody-dependent enhancement of dengue-2 virus in people of white descent in Cuba. Lancet 1987; i: 1028-1029.
    65. Bhamarapravati N, Yoksan S. Live attenuated tetravalent dengue vaccine In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 367-377.
    66. Kinney RM, Butrapet S, Chang GJ, et al. Construction of infectious cDNA for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53. Virology 1997; 230: 300-308. CrossRef
    67. Trent DW, Kinney RM, Huang CY-H. Recombinant dengue virus vaccines In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 379-403.
    68. Chambers TJ, Tsai TF, Pervokov Y, Monath TP. Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting. Vaccine 1997; 15: 1494-1502. CrossRef
    69. Reiter P, Gubler DJ. Surveillance and control of urban dengue vectors In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 425-462.
    70. Gubler DJ, Clark GG. Community-based integrated control of Aedes aegypti: a brief overview of current programs. Am J Trop Med Hyg 1994; 50 (suppl 6): 50-60. MEDLINE
    71. Winch P, Kendall C, Gubler DJ. Effectiveness of community participation in vector-borne disease control. Health Policy Planning 1992; 7: 342-351.
    72. Rosenbaum J, Nathan MB, Ragoonanansingh R, et al. Community participation in dengue prevention and control: a survey of knowledge, attitudes and practice in Trinidad and Tobago. Am J Trop Med Hyg 1995; 53: 111-117. MEDLINE
    73. Gordon AJ, Rojas Z, Tidwell M. Cultural factors in Aedes aegypti and dengue control in Latin America: a case study from the Dominican Republic. Int Quart Community Hlth Educ 1990; 10: 193-211.
    74. Winch P, Lloyd L, Godas MD, Kendall C. Beliefs about the prevention of dengue and other febrile illnesses in Merida, Mexico. J Trop Med Hyg 1991; 94: 377-387. MEDLINE
    75. Whiteford LM. The ethnoecology of dengue fever. Med Anthropol Q 1997; 11: 202-223.
    76. Lloyd LS, Winch P, Ortega-Canto J, Kendall C. The design of a community-based health education intervention for the control of. Aedes aegypti. Am J Trop Med Hyg 1994; 50: 401-411.
    77. Winch P, Lloyd LS, Hoemeke L, Leontsini E. Vector control at the household level: an analysis of its impact on women. Acta Trop 1994; 56: 327-339. MEDLINE | CrossRef
    78. Gordon AJ. Mixed strategies in health education and community participation: an evaluation of dengue control in the Dominican Republic. Health Educ Res 1998; 3: 399-419.
    79. Leontsini E, Gil E, Kendall C, Clark GG. Effect of a community-based Aedes aegypti control programme on mosquito larval production sites in El Progreso, Honduras. Trans R Soc Trop Med Hyg 1993; 87: 267-271. MEDLINE | CrossRef
    80. Schofield CJ. The politics of malaria vector control. Bull Ent Res 1993; 83: 1-4.
    81. Rigau-P?rez JG, Gubler DJ. Surveillance for dengue and dengue hemorrhagic fever In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, UK: CAB International, 1997: 405-423.
    82. Halstead SB, Shepard DS. Dengue (with notes on yellow fever and Japanese encephalitis) In: , Jamison DT, ed. Disease control priorities in the developing countries. New York: Oxford University Press, 1993: 303-320.
    83. Meltzer MI, Rigau-P?rez JG, Clark GG, Reiter P, Gubler DJ. Using disability-adjusts life years to assess the economic impact of dengue in Puerto Rico: 1984?1994. Am J Trop Med Hyg 1998; 59: 265-271.
    Back to top

  • #2
    Figure 1


    Figure 1. World distribution of dengue

    Comment


    • #3
      Figure 2


      Figure 2. Warning signs for dengue shock

      Comment

      Working...
      X