Dengue
fever is an acute febrile infectious disease, caused
by all four serotypes (1, 2, 3 or 4) of a virus from
genus Flavivirus, called dengue virus. It’s the
most prevalent flavivirus infection of humans, with
a worldwide distribution in the tropics and warm areas
of the temperate zone, corresponding to that of the
principal vector, Aedes aegypti.
When simultaneous or sequential introduction of two
or more serotypes occurs in the same area, there may
be an increased number of cases with worse clinical
presentation (dengue hemorrhagic fever). The term ‘hemorrhagic’
is imprecise, because what characterizes this form of
the disease is not the presence of hemorrhagic manifestations,
but the abrupt increase of capillary permeability, with
diffuse capillary leakage of plasma, hemoconcentration
and, in some cases, with non-hemorrhagic hypovolemic
shock (dengue shock syndrome).
Epidemiology:
The highest incidence of dengue is in southeast Asia,
India and the American tropics, where Aedes aegypti
can be found. In areas such as southeast of Asia, where
all four dengue virus types are hyperendemic, children
are almost exclusively affected, and seroprevalence
approaches 100% by young adulthood.
Transmission occurs by the bite of Aedes aegypti female
mosquitoes - the same vector of urban yellow fever -
a day-active species with low fly-autonomy that is abundant
in and around human habitations. In Brazil and other
countries Aedes albopictus may also be responsible for
transmission. Viremic humans (till the fifth day of
disease) serve as the source of virus for mosquito infection;
transmission is not from person-to-person. Movement
of viremic humans provides the principal means of spread,
and rapid air travel is a factor in most recent epidemics.
Although homotypic immunity is complete and lifelong,
cross-protection between virus types is incomplete and
transient. As mentioned before, there is a strict association
between reinfection by another serotype and the occurrence
of dengue hemorrhagic fever (DHF), due to immunopathologic
processes, such as immune enhancement and immune clearance.
Outbreaks usually occur in summer, when ambient conditions
are ideal for proliferation of vectors.
Clinical Manifestations:
Incubation period: 3 - 6 days;
some cases may reach 15 days. Dengue Fever:
Symptoms begin with the abrupt onset of high fever, severe
malaise, headache, retro-orbital pain, myalgia (lumbosacral
pain, also involving legs), frequently accompanied by
sore throat, nausea, vomiting, epigastric pain and diarrhea.
In children, sore throat and abdominal pain are predominant.
Defervescence occurs between days 3 and 8, usually followed
by minor hemorrhagic phenomena (petechiae, purpura, epistaxis)
and the onset of a maculopapular or morbilliform, sometimes
pruritic rash on the trunk, with a centrifugal spread
involving limbs, face, palms and soles. Some cases may
advance with severe gastrointestinal bleeding and shock.
Thus, the presence of hemorrhagic manifestations is not
exclusively for ‘dengue hemorrhagic fever’. Dengue Hemorrhagic Fever (DHF):
The early phase of illness is indistinguishable from dengue
fever. After 2 - 5 days, however (defervescence period),
a few cases in the first infection, in contrast with a
significant number of cases after reinfection by another
serotype may present with thrombocytopenia (< 100.000
/mm3) and hemoconcetration, the first usually preceding
the second. Hemorrhagic manifestations may or may not
occur; the spleen is not palpable, but hepatic enlargement
and tenderness is a sign of bad prognosis. Other manifestations
include pleural effusion and hypoalbuminemia, encephalopathy
with normal cerebrospinal fluid.
Diffuse capillary leakage of plasma is responsible for
the haemoconcentration. In the presence of haemoconcentration
and thrombocytopenia, the patient is considered to be
affected by dengue hemorrhagic fever and classified according
to the following World Health Organization classification: Grade I - thrombocytopenia + hemoconcentration.
Absence of spontaneous bleeding. Grade II - thrombocytopenia + hemoconcentration.
Presence of spontaneous bleeding. Grade III - thrombocytopenia + hemoconcentration.
Hemodynamic instability: filiform pulse, narrowing of
the pulse pressure (< 20 mmHg), cold extremities, mental
conffusion. Grade IV - thrombocytopenia + hemoconcentration.
Declared shock, patient pulseless and with arterial blood
pressure = 0 mmHg (dengue shock syndrome - DSS).
The case-fatality of DHF/DSS is 10% or higher if untreated.
With supportive treatment, less than 1% of such cases
succumb. Recovery is rapid and without sequelae.
Who's most at risk of contracting
anthrax?
Anthrax is an occupational hazard
of; workers who process animal hides, hair, bone and bone
products; agricultural workers; vets; and those working
with anthrax in specialist laboratories.
Does a person have to get vaccinated?
A vaccination against anthrax
is available but it is only recommended for those people
at highest risk. It is not recommended for the general
public.
If a suspicious package or letter
has been received, what should be done?
If a suspicious package or letter
is received, it should not be opened. The local police
station must be informed for suitable advice and action.
Why is Anthrax the "weapon"
of choice for bio-terrorism?
Anthrax tops the list of weapons
for bio-terrorism because the disease caused by inhaling
it is usually fatal if left untreated. It is relatively
easy to get hold of the causative organism; the spores
are stable and can be dispersed by anything from a letter
to a bomb; and the symptoms look harmless that they may
be missed and it may become too late before the condition
is recognized.
The disadvantage of using this organism as a weapon
is that anthrax is not easy to process into a usable
form and the condition is easily treatable with antibiotics.
Diagnosis:
Although the etiologic diagnosis
of dengue is extremely important and desirable in terms
of Public Health Care, it is absolutely unnecessary for
the early institution of supportive therapy. Dengue is
always a diagnosis of exclusion, and other diseases with
the same initial clinical presentation must be suspected.
In order to help the clinician in the detection of severe
forms of dengue (DHF/DSS), even when the definitive diagnosis
has not been made yet, there are three essential laboratory
tests that may help in the evaluation of the real clinical
conditions of the patient and its early supportive management:
total white blood cells count,
total platelets count and
micro-hematocrit. Laboratory Findings:
Total White Blood Cells Count: In case of dengue, this
test will reveal leukopenia. The presence of leukocytosis
and neutrophilia excludes the possibility of dengue and
bacterial infections (leptospirosis, meningoencephalitis,
septicemy, pielonephritis etc.) must be considered.
Thrombocytopenia (< 100.000 /mm3): Total platelets
count must be obtained in every patient with symptoms
suggestive of dengue for three or more days of presentation.
Leptospirosis, measles, rubella, meningococcemia and septicemy
may also course with thrombocytopenia.
Hematocrit (micro-hematocrit): According to the definition
of DHF, it’s necessary the presence of hemoconcentration
(hematocrit elevated by > 20%); when it’s not
possible to know the previous value of hematocrit, we
must regard as significantly elevated the results >
45%.
Etiologic Confirmation:
It can be obtained by isolating infectious virus, demonstrating
viral antigen by immunoassay, or viral genome by PCR in
serum or blood.
Serologic diagnosis is achieved by IgM antibody-capture
by enzyme-linked immunosorbent assay (MAC - ELISA) in
two blood specimen taken in a period of 14 days from each
other. The first specimen, taken till the seventh day
of the disease, can also be useful for virus isolation
by inoculation of Aedes albopictus cells or adults mosquitoes,
with specific identification of virus by immunofluorescence
tests employing monoclonal antibody reagents.
Postmortem diagnosis is made by virus isolation or by
demonstration of viral antigen (direct immunofluorescence)
from two-specimen visceral fragments (liver, spleen, lymph
nodes, thymus).
Treatment :
Pharmacological
Therapy for Bacillus Anthracis Infection
Therapy
Dosage for Adults
Dosage for Children
Treatment of Infection*
Penicillin V
200-400 mg orally 4 times/day
25-50 mg/kg of body weight/day orally
in divided doses 2 to 40 times/day
Penicillin V
8 million-12 million U total, intravenously
in divided doses every 4-6 hr
100,000-150,000 U/kg/day in divided
doses every 4-6 hr
Streptomycin
30 mg/kg intramuscularly or intravenously
per day
Tetracycline
250-500 mg orally or intravenously
4 times/day
Tetracycline is not approved for
children
Doxycycline
200 mg orally or intravenously as
a loading dose, then 50-100 mg every 12 hr
Doxycycline is not approved for children
<9 yr old
Ciprofloxacin
250-750 mg orally twice/day; 200-400
mg intravenously every 12 hr
20-30 mg/kg/day in divided doses
every 12 hr; oral or intravenous dosing is not approved
for patients <18 yr old
Prophylaxis
Doxycycline
100 mg orally twice/day for 4 wk
Ciprofloxacin
500 mg orally twice/day for 4 wk
Corticosteriod
therapy for severe edema
Dexamethasone
0.75-0.90 mg/kg/day orally, intravenously,
or intramuscularly in divided doses every 6 hr
0.25-0.5 mg/kg every 6 hr
Prednisone
1-2 mg/kg or 5-60 mg orally/day
0.5-2 mg/kg/day
Differential Diagnosis:
Leptospirosis - Increased
erythrocyte sedimentation rate, total WBC elevated with
neutrophilia, transaminases levels slightly elevated and
increased BUN and serum creatinine. The presence of jaundice
(indicative of severe forms of leptospirosis) + epidemiological
data practically exclude the diagnosis of dengue. Respiratory Infections - ‘Common cold’
is seldom mistaken with dengue due to the absence of fever.
In relation to the ‘Influenza-like syndromes’,
differential diagnosis is made by the presence of respiratory
symptoms (cough, sore throat, nasal discharge), with higher
incidence in the winter; Bacterial pneumonias usually
present with chest pain (pleurodynia), produtive cough
and total WBC elevated with neutrophilia. Diagnosis can
be made by chest radiography and examination of sputum
for bacteria by the method of Gram. Measles - The pre-exanthematic phase (cough, nasal
discharge, conjuntivitis) doesn’t occurs in dengue.
The morbilliform rash usually begins on the face, with
a cefalo-caudal progression. The presence of ‘Koplik’
lesions in the mucous membrane just before the exanthematic
phase is a pathognomonic sign of measles. A positive vaccination
history doesn’t exclude the diagnosis, because an
inadequate immunization may have occurred.
Rubella (German measles) - Fever with an insidious onset,
absence of systemic symptoms and lymphadenopathy (retroauricular,
suboccipital, cervical) preceding a rash which usually
begins on the face are typical of rubella. The diagnosis
of rubella cannot be made on clinical basis, but by serologic
methods. Malaria - Diagnosis is made by detection of Plasmodium
forms on serial blood examination. Fever in malaria is
initially of daily presentation, and spleen may be enlarged
and tender; jaundice may also be present. Yellow Fever - The initial clinical manifestations
are indistinguishable from dengue. However, the period
of incubation usually doesn’t exceed 6 days. Laboratory
findings include leukopenia and neutrophilia, a very low
erythrocyte sedimentation rate and a marked increase in
the serum transaminases levels. A positive vaccination
history practically excludes the diagnosis of yellow fever. Meningoencephalitis - Headache, presence of petechiae
and shock with an onset < 24 - 48 hours indicate the
obligatory exclusion of meningococcemia (in the severe
forms of dengue these manifestations usually occur after
the third day of disease). Leukocytosis and neutrophilia,
thrombocytopenia and haemoconcentration may be present.
Besides, neurological manifestations tend to be absent
in dengue fever, in contrast with meningoencephalitis.
The evaluation of the cerebral spinal fluid is the basis
of diagnosis, because in dengue fever the CSF is usually
normal. Pyelonephritis - The diagnosis is made based on
the urine culture and Gram study. Urine analysis is inadequate
for the evaluation of the urinary tract infections. WBC
may show leukocytosis and neutrophilia. Septicemia - The onset of symptoms is more insidious
and it’s usually possible for the clinician to detect
a primary infectious focus. Splenomegaly, leukocytosis/
leukopenia, metabolic acidosis and neurological disturbances
may be present. Related diseases like diabetes mellitus,
alcoholism, neoplasms and malnutrition may lead to the
correct diagnosis, which is made by blood cultures.
Treatment:
No specific treatment of dengue
is available. Early institution of supportive treatment
(fluids replacement and correction of electrolyte imbalances)
is the key to management of patients with dengue in all
its forms, since high fever, anorexia, vomiting and capillary
leakage result in some degree of dehydration.
A. Criteria For Home Observation:
All cases of dengue fever with no need of IV fluids
replacement;
Patients regarded as Grade I capable of receiving Oral
Fluids Replacement Therapy (OFRT);
Patients regarded as Grade II capable of receiving OFRT
and without important bleedings.
B. Criteria For Short-Duration Admission In Hospital
(12 - 24 hours):
All cases of dengue fever that need IV fluids replacement;
Patients regarded as Grade I without response to OFRT;
Patients regarded as Grade II without response to OFRT;
Patients regarded as Grade I or II with hepatic tenderness;
All patients regarded as Grade III.
C. Criteria For Long-Duration Admission In Hospital
(> 24 hours):
Patients with no response to fluids replacement therapy
after short-duration admission;
Patients regarded as Grade I or II with predisposing
factors to develop severe forms of presentation (asthma,
allergies, diabetes mellitus, chronic obstructive pulmonary
diseases)
Patients regarded as Grade II or III with bleeding;
All patients regarded as Grade IV.
Intensive monitoring of vital signs and markers of haemoconcentration,
replacement of intravascular volume with lactated Ringer’s
solution or isotonic saline, correction of metabolic
acidosis, and O2 therapy is life-saving in patients
with DSS. Once the patient is stabilized and capillary
leakage stops and resorption of extravasated fluid begins,
care must be taken not to induce pulmonary edema with
continued intravenous fluid administration.
In relation to symptomatic therapy, salicylates should
be avoided because of the potential bleeding diathesis
and because dengue has been associated with Reye syndrome
in a few cases.
Prognosis:
As mentioned in section III, with
early supportive treatment, the majority of cases recover
rapidly and without sequelae. Hospitalized patients can
return their houses after 2 days without fever; all patients
often experience prolonged convalescence with generalized
asthenia and depression lasting several weeks. Prevention:
In areas infested with Aedes aegypti, patients should
be safeguarded from mosquito bite;
Measures must be taken to combat urban vectors (with
insecticides, by avoiding or covering water storage
in and around houses). It is important to remember
that Aedes aegypti is a domestic mosquito, which bites
during the morning or afternoon and has a low fly-autonomy
(200 m), different from Culex sp.;
There is no vaccine available at the moment, although
experimental live, attenuated vaccines developed in
Thailand against all four serotypes have been tested
clinically; various approaches to genetically engineered
vaccines are also being explored.
Picture Quiz
Dengue
fever is an acute febrile infectious disease, caused
by all four serotypes (1, 2, 3 or 4) of a virus from
genus Flavivirus, called dengue virus. It’s the
most prevalent flavivirus infection of humans, with
a worldwide distribution in the tropics and warm areas
of the temperate zone, corresponding to that of the
principal vector, Aedes aegypti.