DENGUE HEMORRHAGIC FEVER

Introduction: 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 µhemorrhagic¶ 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 A. aegypti can be found. In the 1980s, dengue emerged in explosive epidemics in Rio de Janeiro (1986 - serotype 1 and 1990 - serotype 2 was isolated in Niterói city), São Paulo and in many other towns and cities in Brazil. 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; there is not person-to-person transmission. Movement of viremic humans provides the principal means of spread, and rapid air travel is a factor in most recent epidemic emergences. 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 (see bibliography). Outbreaks usually occur in summer, when ambiental conditions are ideal for vectors¶ proliferation. Clinical Manifestations: Incubation period: 3 - 6 days; some cases may reach 15 days. Dengue Hemorrhagic Fever (DHF):

Grade II . however (defervescence period). encephalopathy with normal cerebrospinal fluid. y . Hemodynamic instability: filiform pulse. a few cases in the first infection. y The case-fatality of DHF/DSS is 10% or higher if untreated. Thrombocytopenia (< 100. Laboratory Findings: y Total White Blood Cells Count: In case of dengue. In order to help the clinician in the detection of severe forms of dengue (DHF/DSS). Recovery is rapid and without sequelae. With supportive treatment. measles. meningoencephalitis.000 /mm3): Total platelets count must be obtained in every patient with symptoms suggestive of dengue for three or more days of presentation. The presence of leukocytosis and neutrophilia excludes the possibility of dengue and bacterial infections (leptospirosis.thrombocytopenia + hemoconcentration. Leptospirosis. cold extremities. Diagnosis: Although the etiologic diagnosis of dengue is extremely important and desirable in terms of Health Public Care.thrombocytopenia + hemoconcentration.thrombocytopenia + hemoconcentration. patient pulseless and with arterial blood pressure = 0 mmHg (dengue shock syndrome .000 /mm3) and hemoconcetration. Grade IV . the patient is considered to be seized by dengue hemorrhagic fever and classified according to the following World Health Organization classification: y y y Grade I .The early phase of illness is indistinguishable from dengue fever. Other manifestations include pleural effusion and hypoalbuminemia.thrombocytopenia + hemoconcentration. After 2 . Diffuse capillary leakage of plasma is responsible for the hemoconcentration. this test will reveal leukopenia. it¶s absolutely unnecessary for the early institution of supportive therapy. Absence of spontaneous bleeding. Grade III .DSS). total platelets count and micro-hematocrit.5 days. In the presence of hemoconcentration and thrombocytopenia. narrowing of the pulse pressure (< 20 mmHg). in contrast with a significant number of cases after reinfection by another serotype may present with thrombocytopenia (< 100. rubella. but hepatic enlargement and tenderness is a sign of bad prognosis. pielonephritis etc. even when the definitive diagnosis has not been made yet. fewer than 1% of such cases succumb. and other diseases with the same initial clinical presentation must be suspected. the first usually preceding the second. 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. Presence of spontaneous bleeding. Hemorrhagic manifestations may or may not occur. Dengue is always a diagnosis of exclusion. meningococcemia and septicemy may also course with thrombocytopenia. Declared shock. septicemy.) must be considered. the spleen is not palpable. mental conffusion.

it¶s necessary the presence of hemoconcentration (hematocrit elevated by > 20%). thymus). B. albopictus cells or adults mosquitoes.y Hematocrit (micro-hematocrit): According to the definition of DHF.24 hours): y All cases of dengue fever that need intravascular fluids replacement. when it¶s not possible to know the previous value of hematocrit. Criteria For Home Observation: y All cases of dengue fever with no need of intravascular fluids replacement. anorexia. C. taken till the seventh day of the disease.ELISA) in two blood specimen taken in a period of 14 days from each other. y Patients regarded as Grade I capable of receiving oral fluids replacement therapy (OFRT). y All patients regarded as Grade III. Criteria For Long-Duration Admission In Hospital (> 24 hours): . y Patients regarded as Grade II capable of receiving OFRT and without important bleedings. A. The first specimen. Criteria For Short-Duration Admission In Hospital (12 . or viral genome by PCR in serum or blood. with specific indentification of virus by immunofluorescence tests employing monoclonal antibody reagents. demonstrating viral antigen by immunoassay. 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. linfonodes. spleen. can also be useful for virus isolation by inoculation of A. y Patients regarded as Grade I or II with hepatic tenderness. Etiologic Confirmation: It can be obtained by isolating infectious virus. we must regard as significantly elevated the results > 45%. vomiting and capillary leakage result in some degree of dehydration. Serologic diagnosis is achieved by IgM antibody-capture by enzyme-linked immunosorbent assay (MAC . since high fever. Postmortem diagnosis is made by virus isolation or by demonstration of viral antigen (direct immunofluorescence) from two-specimen visceral fragments (liver. Treatment: No specific treatment of dengue is available.

Croatia. References: y http://nurses. she experienced a 3day episode of fever that spontaneously resolved but without laboratory evidence of dengue.php/2010/08/all-about-dengue-hemorrhagic-fever/ y http://hubpages. A 33-year-old Spanish woman who had worked in Anantapur.cdc. Two months previously.definitelyfilipino. transmitted by infectedAedes mosquitoes. on holiday. y Patients regarded as Grade I or II with predisposing factors to develop severe forms of presentation (asthma. care must be taken not to induce pulmonary edema with continued intravenous fluid administration. correction of metabolic acidosis.com/hub/Dengue_Hemorrhagic_Fever Article: Imported Dengue Hemorrhagic Fever. she traveled to Dubrovnik. Once the patient is stabilized and capillary leakage stops and re-absorption of extravasated fluid begins. the presence of non-neutralizing antibodies increases the risk for progression to dengue hemorrhagic fever (DHF) or dengue shock syndrome when the patient is infected by any of the other 3 serotypes. returned to Spain on August 1. allergies. replacement of intravascular volume with lactated Ringer¶s solution or isotonic saline. On August . on August 3. We report an imported case with severe clinical manifestations that fulfills DHF criteria. chronic obstructive pulmonary diseases) y Patients regarded as Grade II or III with important bleedings. attenuated vaccines developed in Thailand against all four serotypes have been tested clinically. y Combat against the urban vectors (insecticides. for 180 days. Intensive monitoring of vital signs and markers of hemoconcentration.htm) Dengue infection is an endemic and epidemic urban disease. y All patients regarded as Grade IV. avoid water storages inside and around houses). patients should be safeguarded from mosquito bite. Prevention: y In areas infested with A. and 2) the spread of the 4 serotypes and the vector in diseaseendemic areas. y There¶s no vaccine available at the moment. diabetes mellitus.gov/eid/content/14/8/1329. various approaches to genetically engineered vaccines are also being explored. and after a few months.com/index. Europe María Jesús Pinazo (http://www. and O2 therapy is life-saving in patients with DSS. She also had visited Thailand 45 days before August 1 and Brazil 2 years ago. although experimental live.y Patients with no response to fluids replacement therapy after short-duration admission. Its incidence is increasing in tropical and subtropical areas because of 1) introduction of the virus into areas where it was not previously endemic. Infection with 1 serotype provides lifelong homologous immunity only for that serotype. aegypti. 2007. India.

AST 347 U/L. chikungunya. Positive IgG were 1:320 (type 1) and 1:100 (type 3 and 4). parvovirus B19. Frequent travelers are more at risk for DHF. a confluent maculopapular rash developed. DHF diagnosis. Three days later. Hantaan. Since 1977.000. packed cell volume (PCV) 41. and Dobrava viruses.4 s. leukocyte count 1.6. platelet count was 50 × 109/L. Puumala. Few cases of reported DHF fulfill criterion 3 due to the short duration of severe thrombocytopenia in mild clinical forms. The patient was treated with fluid and plasma replacement. on the basis of her clinical symptoms. LDH 544 U/L. The 4 World Health Organization (WHO) criteria for DHF diagnosis are 1) fever related to the current process. The patient was transferred to Barcelona (Spain) University Hospital on August 14. In a recent European publication. and lactate dehydrogenase (LDH) 198 U/L. gamma-glutamyl transferase 114 U/L. Because viral hemorrhagic fever was suspected. in view of the increase of DHF numbers (2006±2007) and several outbreaks around the world. She exhibited headache. antipyretics. platelet count 97 × 109/L. thorax.6%. Increased vascular permeability was shown in our patient by the peritoneal and bilateral pleural effusions. headache. as in our case. alanine aminotransferase (ALT) 31 U/L. . with hypotension and was admitted to the hospital. Urine. and 4. 17% of patients with imported dengue fever exhibited a secondary immune response. Chest radiograph and abdominal ultrasound scan showed bilateral pleural and peritoneal effusions.6 fL. Dubrovnik hospital laboratory values were hemoglobin (Hb) 143 g/L. and ceftriaxone plus doxycycline to counteract bacterial and other possible tick-borne infections.96 × 109/L. The fever subsided 9 days after the onset of symptoms. aspartate aminotransferase (AST) 45 U/L. with diffuse petechiae and bruising. ALT 322 U/L. bilirubin 0. Our patient fulfilled all 4 criteria. hemorragic fever was suspected. 3) low levels of platelets (<100 × 109/L) and 4) increased capillary permeability. thus having a higher risk of developing DHF in the future. alkaline phosphatase 194 U/L. 2. On the fifth day of illness. Clinical examination showed a maculopapular rash involving the face. Barcelona University Hospital laboratory values were Hb 105 g/L. A second sample on day 11 showed all 4 IgG serotypes >1:10. HIV 1 and 2. Dengue virus infection should therefore be considered in the differential diagnosis of fever in returning travelers. prothrombin time 12. and myalgia. MCV 86. and IgM >1:10. 2) hemorrhagic manifestations. Epstein-Barr virus. arthralgia. or rickettsial diseases. Platelet count and renal function were within normal limits. although unusual. yellow fever. even during the nondengue season. cytomegalovirus. Results of real-time PCR for CCHF were negative but reverse transcription±PCR multiplex for dengue virus was positive for dengue type 1 virus. chills. Serologic tests on day 3 and day 11 after the onset of symptoms were not reactive for Crimea-Congo hemorrhagic fever (CCHF). and myalgia. and palms and soles. and stool cultures were all negative for bacterial infections. could become more frequent in the future. PCV 32%.5 mg/dL.000 for serotypes 1. she exhibited a high fever. Immunoglobulin (Ig) M tests on day 3 for all 4 dengue virus serotypes were negative. blood. arthralgia. The patient recovered and was monitored for 2 months. The probability of diagnosing dengue fever in Europe increases with travel to dengue-endemic areas. the patient was referred to a specialized hospital in Zagreb. mean corpuscular volume (MCV) 84. She was placed under strict isolation measures while awaiting final diagnosis. 15 cases of imported DHF have been reported in Europe. AP 73 U/L. limbs. Serologic tests confirm dengue infection only if a 4-fold increase in titers in consecutive serum samples occurs.93 mg/dL. and C-reactive protein level 6.