Dengue is an endemic
tropical viral disease in many areas in the World including the
Caribbean and the Americas. Although cases may be detected all
year-round, the number of cases is clearly related to cyclic changes in
weather: an increase in the number of cases usually follows the onset of
the rainy season. Occasionally this gives rise to major outbreaks that
may involve one or more Caribbean islands.
The
agent of Dengue is the Dengue virus, a member of the Flavivirus group.
There are four acknowledged types of Dengue Viruses designated as types
1, 2, 3 and 4. Although these four types share common antigens,
antibodies against each of these types are only able to neutralize the
same type that elicited the response. Periodic epidemics are associated
with the emergence or re-emergence of different serotypes. On average in
the Caribbean major outbreaks by a given type tend to re-occur in the
same country every decade. Also the reinfection of an individual by a
different type (heterotypic reinfection) may trigger complex
immunopathologic mechanisms leading to the two most severe
manifestations of the disease: Dengue Haemorrhagic Fever (DHF) and
Dengue Shock Syndrome (DSS).
Dengue
Viruses are transmitted by mosquitoes of the Aedes group. These are
relatively small mosquitoes that feed exclusively in humans.
Predominantly on humans and less so on other animals. They tend to bite
during the day and are usually found resting in dark places inside human
housing. They breed in small deposits of relatively clean water in or
around human housing (flower pots, saucers under plant pots, old tires,
etc.)
Currently,
Dengue virus types 1, 2, 3 and 4 are circulating in the Caribbean.
Dengue type 3 re-emerged in CAREC Member Countries (CMCs) in 1998 after
several decades of absence from the region. Type 3 isolates have been
detected in several CMCs to date, including, Jamaica, Belize, Barbados,
British Virgin Islands, Antigua, Dominica and St. Kitts and Nevis.
Description
Dengue Fever
Clinical Description
Sudden onset
High fever (> 100° F)
Headache / myalgias
Retro-orbital pain
Lymphadenopathies (cervical/occipital)
Maculo-papular rash
Other associated elements may include upper/lower respiratory involvement, pharyngitis, vomiting and diarrhea
Haematology laboratory results
Leukopenia
Differential diagnosis
Influenza
Acute viral exanthems (Measles, Rubella)
Leptospirosis
Dengue Haemorrhagic Fever (DHF)
Clinical description
Possibly more frequent in children and young adults
Similar onset as Dengue Fever
Complications usually start when fever subsides
Facial flush
Epigastric and abdominal pain
Hepatomegaly
Haemorrhagic tendencies
Petechiae, Bruises, Hematuria, Hematemesis, Epistaxis, Melena/Blood in stools, Gingival bleeding
Positive tourniquet test
Haematology laboratory tests
Platelet count < 100,000/mm3
Elevated haematocrit (hemoconcentration) > 20% the average value for the age
Differential diagnosis
Leptospirosis
Acute abdomen
Other forms of purpura or viral hemorrhagic diseases
Dengue Shock Syndrome (DSS)
Clinical description
Similar onset as Dengue Fever
Patient deteriorates after a few days of fever
Cold, clammy skin, cyanosis
Tachycardia, low pulse pressure or hypotension
Abdominal tenderness
Recurrent lipothymias (repeated fainting)
Altered mental status (restlessness)
Oliguria
Hypotension
Encephalopathy
Coma
Laboratory results
Increased hematocrit (hemoconcentration)
Metabolic acidosis
Differential diagnosis
Acute abdomen
Septicemia
Acute Meningoccemia
Case definitions
(When met, the cases are reportable to Public Health authorities)
Dengue Fever (DF)
Probable
An acute febrile illness with two or more of the following manifestations:
Headache
Retro-orbital pain
Myalgias
Arthralgias
Rash
Haemorrhagic manifestations
Occurring at the same location and time as other confirmed cases of dengue.
Confirmed
A case with at least one of the following:
- An Haemagglutination In hibition titer equal or higher than 1280
- Sero-conversion (four-fold change in titer) by haemagglutination inhibition
- Positive for IgM anti-Flavivirus antibodies during a time consistent with the occurrence of the disease
- Isolation and typing of a dengue virus from an early blood specimen.
Dengue Hemorrhagic Fever (DHF)
Probable
Recent history of fever
Haemorrhagic tendencies (see above)
Thrombocytopenia at or below 100.000/ mm3
Haematocrit 20% above average for that age, sex and population
Confirmed
Add the same criteria as for confirmed cases of DF.
Dengue Shock Syndrome (DSS)
Probable
All four criteria for DHF plus elements of shock:
Cold, clammy skin
Rapid weak pulse
Narrow pulse pressure or hypotension
Confirmed
Add the same criteria as for confirmed cases of DF
Laboratory Diagnosis
General laboratory
One
clinical manoeuvre (tourniquet test) and two laboratory studies
performed in a general laboratory (platelet counts and hematocrit) are
crucial to the diagnosis of dengue hemorrhagic fever: These studies
should be requested as soon as DHF/DSS is suspected and should be
repeated as appropriate during the follow-up of the patient. If
hematocrit is not available, haemoglobin determination can be used to
detect hemoconcentration , however, it is usually less sensitive.
Specialized laboratory
CAREC offers the following virological tests for confirmation of DF/DHF/DSS:
Virus isolation (serum taken within 3 days after onset)
This
study requires serum taken from the patient within three days of onset
(hence the importance of indicating the date of onset and the date of
collection in the submitting form). The serum should be separated from
the clot and should never be frozen but should be kept refrigerated (4°
C) or on ice until its reception in CAREC. This test may take several
weeks as it requires serial passages in tissue cultures (in mosquito
cell lines).
IgM ELISA (serum taken after 1 week of onset)
IgM
antibodies rise quickly and fade down several weeks after the
infection. Although IgM antibodies can appear very fast after infection,
they can be consistently detected in most patients only after the first
week. CAREC recommends the use of sera taken at least five days after
onset. In earlier sera the result is diagnostic only if positive. A
positive results indicates that the patient has been exposed to the
virus in the recent past. The test is unable to identify the viral type.
Strictly speaking, the test is not specific to Dengue as there can be
cross-reaction with other Flavivirus as (Yellow Fever, Yellow Fever
Vaccination and other Flavivirus or more rare occurrence in the
Caribbean). However, in conjunction with the clinical presentation and
the epidemiological knowledge it can strongly support the diagnosis of
Dengue virus infection.
Hemagglutination Inhibition Assay (HAI) (acute serum if DHF/DSS is suspected)
This
test detects IgG antibodies. If paired sera are provided it can be used
to determine HAI titers in both the acute and convalescent sera and a
four-fold increase in titer is diagnostic of primary dengue infection.
Often individuals that were previously infected by a different Dengue
virus type will have very high titers in their acute serum (equal or
higher than 1280). This test is provided for cases suspected of DHF/DSS,
but results are delayed in comparison with Dengue IgM.
Information required by the laboratory
The
submission form to accompany a sample should be completed thoroughly.
In particular the laboratory requires data to identify the patient and
the treating physician, the clinical diagnosis, a summary of the signs
and symptoms, a clear indication if DHF/DSS is suspected, the date of
onset, the date of collection and the indication whether Yellow Fever
vaccine has recently been received.
Dengue Laboratory Surveillance
The
laboratory in CAREC is committed to provide the best support available
to the region to predict, detect, investigate, monitor and evaluate
Dengue outbreaks. However, the resources of the laboratory are limited
and need to be strategically assigned. In practical terms this
translates into a strategy for Public Health diagnosis aimed at
maximizing utilization of resources and the impact of laboratory results
while avoiding the overwhelming of laboratory resources. This strategy
consists in the successive application of four mode of laboratory
participation in support of the epidemiological study of Dengue
outbreaks.
1. Baseline mode / No outbreak
Between
outbreaks or in the absence of any recognizable outbreak samples from
all cases suspected of dengue and samples from isolated cases should be
sent to the laboratory for virological confirmation. These samples are
valuable to determine the most prevalent types in each community. Also,
most shifts in the most prevalent type(s) occur during this phase.
When
the number of probable cases with clinical diagnosis of Dengue are
increasing the onset of an outbreak should be suspected. In this
scenario the laboratory requires the fast submission of a sample of
patient sera (<100 sera) drawn
within 3 days after the onset. These sera are required to isolate and
identify the viral type causing the outbreak.
After
the virus causing the outbreak has been identified there is little need
to continue to confirm all cases of dengue fever. In these
circumstances the clinical diagnosis of dengue fever reinforced by the
epidemiological diagnosis should provide the basis for firm diagnosis
and patient management. In these circumstances PAHO recommends the
following:
During
an epidemic when the clinical syndrome and the disease diagnosis are
established and the infecting serotype(s) has/have been identified, it
is a misuse of resources to attempt serologic or virologic confirmation
of every suspected dengue case. Laboratory resources should be focussed
on identifying new areas where the disease might be spreading, detecting
new serotypes coming into already infected areas, and monitoring severe
and fatal cases attributed to dengue.
During this period CAREC suggests the submission of reasonable numbers of two kinds of specimens:
a.
Sera drawn within 3 days of the onset of symptoms for viral isolation
with the purpose of monitoring the prevalence of difference viral types,
and
b. Sera drawn on the
second week after the onset of symptoms with the purpose of using
single-sera IgM ELISA results to monitor the size of the outbreak.
Immediately
following the outbreak, from an epidemiology point of view the Public
Health service of the country may wish to conduct population-based
surveys with the aim, for example, of estimating the true incidence of
the disease. In this case the numbers and type of the samples being
requested will be part of the design of the epidemiological study, to be
determined in consultation with CAREC.
5. Post-outbreak switch / return to baseline mode
After
the outbreak has subsided there is a need to explicitly indicate to
Public Services and physicians the return to the baseline mode, and thus
resume the normal submission of specimens for viral diagnosis.
N.B.: Complicated cases (DHF/DSS)
The
modes outlined above only apply to Dengue Fever cases. Complicated
cases of suspected DHF and DSS should continue to be admissible in the
laboratory throughout the outbreak cycle. In these cases sera should be
submitted to CAREC without delay accompanied by appropriate clinical
data. Virus isolation, IgM Elisa and Haemagglutination inhibition will
be performed as appropriate depending on the date of onset and the date
in which the serum sample was taken.
Note:
CAREC does not offer platelet counts and hematocrit. However, it is
essential that these studies be performed in these patients both for
diagnosis and to monitor their recuperation and convalescence.
Children: Samples from children will be accepted at all times once appropriate information is provided to facilitate testing.
Post-mortem cases
Non-fixed
tissue samples in saline solution or PBS should be submitted to the
laboratory as soon as possible after death. The samples to consider
include heart blood, liver, kidney and spleen).
Patient Management
Note:
In all cases: the patient is infectious to Aedes mosquitos which should
be prevented from feeding on the patient, e.g. through use of an insect
repellent and through use of an insecticide spray inside the house and
bedroom.
Probable diagnosis of Dengue Fever
Home or ambulatory treatment
Analgesics and antipyretics (no aspirin! Due to risk of bleeding)
Paracetamol
1 yr - 60 mg/dose
1-3 yr - 20-120 mg/dose
3-6 yr - 120 mg/dose
6-12 yr - 240 mg/dose
Watch for signs of DHF/DSS (see below)
Probable diagnosis of Dengue Hemorrhagic Fever
Hospitalized (outpatient observation room or rehydration ward)
Analgesics and antipyretics as for the preceeding group
Serial hematocrit and platelet counts (daily)
Fluids ingested by mouth
WHO Oral rehydration solution
Fruit juices
Monitor for signs of shock (shock usually occurs after the third day during transition from febrile to afebrile phases)
I/V
rehydration therapy the fluid and its volume should be determined
according to the degree of dehydration and electrolyte loss.
Probable diagnosis of Dengue Shock Syndrome
Hospitalized (Intermediate treatment room)
Analgesics and antipyretics as for the preceeding group
Serial hematocrit and platelet counts (daily) to monitor treatment and recovery
I/V resuscitation therapy
Ringer's acetate or 5% glucose I PSS at a rate of 10-20 ml/kg of body weight per hour (or as fast as possible).
If shock persists after 20-30 ml/kg of body weight add a plasma expander at the rate of 10-20 ml/kg per hour.
If shock persist significant internal bleeding should be suspected
Continuation
of intravenous therapy should be adjusted according to hematocrit and
the rate should be reduced to 10 ml/kg per hour. In general there is no
need to continue the therapy beyond 48 hours
Table 1
Table 2
(*) These are normal delays after the sample is received in CAREC
(*) Together with Clinical presentation and epidemiological knowledge it confirms a recent exposure to a Dengue virus.
(**) This is the reason to prefer sera taken after the first week.