Dengue Hemorrhagic Fever- A Silent Killer

Dengue is an acute viral illness caused by the RNA virus of the family Flaviviridae, genus Flavivirus, the type-specific virus is yellow fever and spread by Aedes mosquitoes. This virus is a single-stranded RNA virus with 11kilobases, icosahedral nucleocapsid, and covered by a lipid envelope. Although dengue virus infections are usually self-limiting, dengue infection has come up as a public health challenge in the tropical and subtropical nations.

Author Name: Dr. Muhammad Ali Tahir, Dr. Muhammad Akram, Dr. Muhammad Waqas Raza and Dr. Muhammad Muneeb


The dengue virus, a member of the genus Flavivirus of the family Flaviviridae, is an arthropod-borne virus that includes four different serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). The World Health Organization (WHO) considers dengue as a major global public health challenge in the tropic and subtropic nations. Dengue has seen a 30-fold upsurge worldwide between 1960 and 2010, due to increased population growth rate, global warming, unplanned urbanization, inefficient mosquito control, frequent air travel, and lack of health care facilities. Two and a half billion people reside in dengue-endemic regions and roughly 400 million infections occurring per year, with a mortality rate surpassing 5–20% in some areas. The first reported case of dengue-like illness in India was in Madras in 1780, the first virologically proved epidemic of DF in India occurred in Calcutta and Eastern Coast of India in 1963-1964.


DF is a severe flu-like infection that involves individuals of all age groups (infants, children, adolescents, and adults). Transmission among human beings occurs by the mosquito Aedes aegypti and chiefly occurs during the rainy season. The proposed etiologies for dengue virus infection are:

Viral replication, primarily in macrophages, Direct skin infection by the virus

Immunological and chemical-mediated mechanism induced by the host–viral interaction.

Dengue virus gains entry into the host organism through the skin following an infected mosquito bite. Humoral, cellular, and innate host immune responses are implicated in the progression of the illness and the more severe clinical signs occur following the rapid clearance of the virus from the host organism. Alterations in endothelial microvascular permeability and thermoregulatory mechanisms lead to an increased loss of protein and plasma. Proposed theories suggest that endothelial cell activation caused by monocytes, T-cells, the complement system, and various inflammatory molecules mediate plasma leakage. Thrombocytopenia may be related to alterations in megakaryocytopoiesis, manifested by infecting the ion of human hematopoietic cells and impaired progenitor cell growth. This may cause platelet dysfunction, damage, or depletion, leading to significant hemorrhages.

Figure 1 Aedes egypti and Aedes albopictus


The WHO classifies DF into two groups: Uncomplicated and severe. Severe cases are linked to excessive hemorrhage, organ impairment, or severe plasma escape, and the remaining cases are considered uncomplicated. According to the 1997 classification, dengue can be divided into an undifferentiated fever, DF, and DHF.

DHF was further subdivided into grades I–IV.

Grade I: Only mild bruising or a positive tourniquet test

Grade II: Spontaneous bleeding into the skin and elsewhere

Grade III: Clinical sign of shock

Grade IV: Severe shock – feeble pulse, and blood pressure cannot be recorded.

Here, grades III and IV comprise DSS.


Undifferentiated fever

This stage is seen mostly in the primary infection but may also occur following the initial secondary infection. Clinically, it is difficult to differentiate from numerous other viral diseases and often remains undiagnosed.

Dengue fever

Dengue fever follows both primary and secondary infections and is most frequently encountered in adults and older children. The onset of symptoms is characterized by a biphasic, high-grade fever lasting for 3 days to 1 week. Severe headache (mainly retrobulbar), lassitude, myalgia and painful joint, metallic taste, appetite loss, diarrhea, vomiting, and stomachache are the other reported manifestations. Dengue is also known as breakbone fever because of the associated myalgia and pain in joints. Patients with DF, 50–82% report with a peculiar cutaneous rash. The initial rash is the result of capillary dilatation, and presents as transient facial flushing erythema, typically occurring before or during the first 1–2 days of fever. The second rash is seen at 3 days to 1 week following the fever and presents as an asymptomatic maculopapular or morbilliform eruption. Sometimes, individual lesions may merge and present as widespread confluent erythematous areas with pinpoint bleeding spots and rounded islands of sparing, giving a typical appearance of “white islands in a sea of red.”

Dengue hemorrhagic fever

DHF is frequently seen during secondary dengue infection. However, in infants, it may also occur during a primary infection due to maternally attained dengue antibodies.

The proposed diagnosis criteria for DHF include:

  1. Clinical parameters
  2. Laboratory parameters

The clinical course of DHF is characterized by three phases: Febrile, leakage, and convalescent-phase. High-grade fever of acute onset along with constitutional signs and facial erythema characterizes the commencement of the febrile illness. Thrombocytopenia (platelet count <100,000/cu mm).The initial febrile illness is marked by a morbilliform rash and hemorrhagic tendencies. The fever persists for 2 days to 1 week and then drops to normal or subnormal levels when the patient either convalesces or advances to the plasma leakage phase.

 Shock syndrome

DSS is defined as DHF accompanied by an unstable pulse, narrow pulse pressure (<20 mmHg), restlessness, cold, clammy skin, and circumoral cyanosis. Progressively worsening shock, multiorgan damage, and disseminated intravascular coagulation account for a high mortality rate associated with DSS. The shock persists for a short period and the patient promptly recovers with supportive therapy.


Oral features are infrequently seen in dengue virus infection and are more commonly associated with DHF. Erythema, crusting of lips, and tongue and soft palatal vesicles constitute the prominent oral features in dengue virus infection. Brown-colored plaque-like lesions with a rough surface were seen on the buccal mucosa that showed bleeding on touch along with spontaneous bleeding from the gingiva and the tongue.


Cautious attention should be directed at DF if a patient suffers from high fever within 2 weeks of being in the tropics or subtropics. A decreased number of white blood cells (leukopenia), accompanied by a decreased number of platelet count (thrombocytopenia) and metabolic acidosis are the initial changes on laboratory examinations. Microbiological laboratory testing confirms the diagnosis of DF. Virus segregation in cell cultures, a nucleic acid demonstration by polymerase chain reaction (PCR), and serological detection of viral antigens (such as NS1) or particular antibodies are the preferred microbiological assays. Viral segregation and nucleic acid demonstration provide precise diagnosis, although the high cost limits the availability of these tests.


Broad differential diagnosis is considered in a patient presenting with fever and a rash similar to that seen in DF.

Dengue fever must be differentiated from other diseases that prevent flu-like symptoms fever, retro-orbital headache, fatigue, joint aches or arthralgias (joint aches), myalgias (muscle aches), nausea/vomiting, and lymphadenopathy (swollen lymph nodes).

Treatment and Management of dengue fever

  • Fluid replacement and antipyretic therapy with paracetamol is the preferred therapy following the febrile phase.
  • Care should be taken not to use other nonsteroidal anti-inflammatory drugs.
  • Judicious fluid, administration forms the mainstay of treatment during the critical phase of the infection.
  • Normal saline, Ringer’s Lactate, and 5% glucose diluted 1:2 or 1:1 in normal saline, plasma, plasma substitutes, or 5% albumin are the routinely administered fluids.
  • We should need to implement biological and environmental control policies to reduce the population of mosquito and their vectors.

WHO guidelines summarize the following principles of fluid therapy

Oral fluid supplementation must be as plentiful as possible. However, intravenous fluid administration is mandatory in cases of shock, severe vomiting, and prostration (cases where the patient is unable to take fluids orally)

Crystalloids form the first-line choice of intravenous fluid (0.9% saline)

Hypotensive states that are unresponsive to boluses of intravenous crystalloids, colloids (e.g., dextran) form the second-line measures

If the patient remains in the critical phase with low platelet counts, there should be a serious concern for bleeding. Suspected cases of bleeding are best managed by transfusion of fresh whole blood.


Oral lesions are infrequently seen and are often misguided as platelet defects. Significant hemorrhagic manifestations need platelet transfusions. In general, there is no need to give prophylactic platelets even at <20,000/cu mm. Prophylactic platelets may be given at a level of <10,000/cu mm in absence of bleeding manifestations. In case of systemic massive bleeding, platelet transfusion may be needed along with red cell transfusion. Liver functions should be monitored.

Future Policy to reduce the dengue virus attack:

  • Control of mosquito (vector) transmission, development of dengue vaccine, and antiviral drugs constitute future directions intending to prevent and treat dengue infection.
  • Control of mosquito (vector) transmission can be done by keeping guppies (Poecilia reticulata) or copepods (doridicola agilis) in standing water and infecting the mosquito population with bacteria of the Wolbachia genus.
  • Due to the progressing transmission and enhancing the severity of dengue infection, the necessity to develop a dengue vaccine has gained considerable importance.
  • There is a worldwide public health need for a safe, effective, and economic tetravalent dengue vaccine. Complex pathology, the prerequisite to controlling four virus serotypes, and inadequate investment by vaccine designers have hindered vaccine advancement.
  • Scrupulous attempts are aimed to develop antiviral drugs that can be used to manage DF and avoid the life-threatening episodes.

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