Download Dengue and dengue haemorrhagic fever

SEMINAR
Seminar
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.
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
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: [email protected])
THE LANCET • Vol 352 • September 19, 1998
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
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
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Areas infested with Ae aegypti
Countries with recent dengue activity
Figure 1: World distribution of dengue
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 laboratoryconfirmed 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 2·5⳯2·5 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/L), 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
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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.
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,
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Alarm signals
Four criteria for DHF
Fever
Haemorrhagic manifestations
Excessive capillary
permeability
Platelets 105/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.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
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
THE LANCET • Vol 352 • September 19, 1998
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/L.17 Because convalescent-phase
diagnostic samples are often difficult to obtain, a second
blood sample should always be taken on the day of
discharge.
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 ELISA973
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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.
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
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)
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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
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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
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
THE LANCET • Vol 352 • September 19, 1998
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 welldocumented 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
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5
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Further reading
Transmission
General
Christophers SR. Aedes aegypti (L): the yellow fever mosquito: its life
history, bionomics, and structure. London: Cambridge University
Press, 1960.
Gubler DJ. Dengue. In: Monath TP, ed. The arboviruses:
epidemiology and ecology. Boca Raton, FL: CRC Press, 1988, vol II:
223–60.
Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever.
Wallingford, UK: CAB International, 1997.
World Health Organization. Dengue haemorrhagic fever: diagnosis,
treatment and control. Geneva: WHO, 1986.
Pan American Health Organization. Dengue and dengue hemorrhagic
fever in the Americas: guidelines for prevention and control.
Washington, DC: PAHO Sci Publ no 548; 1994.
Clinical Manifestations
Siler JF, Hall MW, Hitchens AP. Dengue: its history,
epidemiology,mechanisms of transmission, etiology, clinical
manifestations, immunity, and prevention. Philippine J Sci 1926; 29:
1–308.
Ramírez-Ronda CH, García CD. Dengue in the western hemisphere. Infect
Dis Clin N Am 1994; 8: 107–28.
Laboratory
Monath TP, Heinz FX, Flaviviruses. In: Fields BN, Knipe DM, Howley PM,
et al. Fields virology. Philadelphia: Lippincott-Raven, 1996:
961–1034.
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Risk factors
Kuno G. Review of the factors modulating dengue transmission.
Epidemiol Rev 1995; 17: 321–35.
Morens DM. Antibody-dependent enhancement of infection and
the pathogenesis of viral disease. Clin Inf Dis 1994; 19:
500–12.
Laboratory
Halstead SB, Gomez-Dantés H, eds. Dengue: a worldwide problem, a
common strategy (Proceedings of International Conference on
Dengue and Aedes aegypti Community-based Control). Mexico City:
Ministry of Health/Rockefeller Foundation, 1992.
Gubler DJ, Clark GG. Community involvement in control of Aedes aegypti.
Acta Trop 1996; 61: 169–79.
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