Dengue Fever: Prevention, Diagnosis & Management

October 8, 2021

Dengue is an acute viral illness caused by a RNA virus of the family Flaviviridae and spread by AEDES mosquitoes.

Presenting features may range from asymptomatic fever to dreaded complications such as hemorrhagic fever and shock. Acute-onset high fever, muscle and joint pain, myalgia, cutaneous rash, hemorrhagic episodes, and circulatory shock are the commonly seen symptoms. Oral manifestations are rare in dengue infection; however, some cases may have oral features as the only presenting manifestation. Early and accurate diagnosis is critical to reduce mortality.

Although dengue virus infections are usually self-limiting, dengue infection has come up as a public health challenge in the tropical and subtropical nations. This article provides a detailed overview on dengue virus infections, varied clinical manifestations, diagnosis, differential diagnosis, and prevention and treatment.

According to the 1997 classification, dengue can be divided into

  • Undifferentiated fever,
  • Dengue Fever – DF
  • Dengue Hemorrhagic – 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.

Dengue Fever

DF follows both primary and secondary infections, and is most frequently encountered in adults and older children. Onset of symptoms is characterized by a biphasic, high-grade fever lasting for 3 days to 1 week.

Severe headache (mainly retro-bulbar), lassitude, myalgia and painful joints, metallic taste, appetite loss, Swollen gland, rash, diarrhea, vomiting, and stomach ache are the other reported manifestations. Dengue is also known as break-bone fever because of the associated myalgia and pain in joints

The initial rash is the result of capillary dilatation, and presents as a 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 a 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.

The cutaneous rash is usually asymptomatic, and pruritus is reported only in 16-27% cases. Bleeding episodes are infrequently seen in DF, although epistaxis and gingival bleeding, substantial menstruation, petechiae/purpura, and gastrointestinal tract (GIT) hemorrhage can occur.

Dengue hemorrhagic fever

Clinical parameters: Acute-onset febrile phase – high-grade fever lasting from 2 days to 1 week. Hemorrhagic episodes (at least one of the following forms): Petechiae, purpura, ecchymosis, epistaxis, gingival and mucosal bleeding, GIT or injection site, hematemesis and/or melena

Positive tourniquet and hepatomegaly.

Laboratory parameters: Thrombocytopenia (platelet count <100,000/cu mm)

Dengue shock syndrome

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

MANAGEMENT OF DENGUE INFECTION

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.

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.
  • High-risk patients having platelet count < 20,000/cumm and risk of bleeding require urgent platelet transfusion. Patients with platelet count 21-50,000/cumm are in moderate risk and require platelet transfusion only if they have any haemorrhagic manifestations and other superadded conditions.

Diagnostic Testing

Nucleic acid amplification tests (NAATs)
  • For patients with suspected dengue virus disease, NAATs are the preferred method of laboratory diagnosis.
    • NAATs should be performed on serum specimens collected 7 days or less after symptom onset.
    • Laboratory confirmation can be made from a single acute-phase serum specimen obtained early (≤7 days after fever onset) in the illness by detecting viral genomic sequences with rRT-PCR or dengue non-structural protein 1 (NS1) antigen by immunoassay.
    • Presence of virus by rRT-PCR or NS1 antigen in a single diagnostic specimen is considered laboratory confirmation of dengue in patients with a compatible clinical and travel history.
Serologic tests
  • IgM antibody testing can identify additional infections and is an important diagnostic tool. However, interpreting the results is complicated by cross-reactivity with other flaviviruses, like Zika, and determining the specific timing of infection can be difficult.
    • Later in the illness (≥4 days after fever onset), IgM against dengue virus can be detected with MAC-ELISA. For patients presenting during the first week after fever onset, diagnostic testing should include a test for dengue virus (rRT-PCR or NS1) and IgM.
    • For patients presenting >1 week after fever onset, IgM detection is most useful, although NS1 has been reported positive up to 12 days after fever onset. In the United States, both MAC-ELISA and rRT-PCR are approved as in vitro diagnostic tests.
    • IgM in a single serum sample strongly suggests a recent dengue virus infection and should be presumed confirmatory for dengue if the infection occurred in a place where other potentially cross-reactive flaviviruses (such as Zika, West Nile, yellow fever, and Japanese encephalitis viruses) are not a risk.
  • PRNTs can resolve false-positive IgM antibody results caused by non-specific reactivity, and, in some cases, can help identify the infecting virus. However, in areas with high prevalence of dengue and Zika virus neutralizing antibodies, PRNT may not confirm a significant proportion of IgM positive results. PRNT testing is available through several state health departments and CDC.

Cross-reactive flaviviruses

If infection is likely to have occurred in a place where other potentially cross-reactive flaviviruses circulate, both molecular and serologic diagnostic testing for dengue and other flaviviruses should be performed.

People infected with or vaccinated against other flaviviruses (such as yellow fever or Japanese encephalitis) may produce cross-reactive flavivirus antibodies, yielding false-positive serologic dengue diagnostic test results.

IgG detection by ELISA in a single serum sample is not useful for diagnostic testing because it remains detectable for life after a dengue virus infection.

DIETARY MANAGEMENT

Things That May Increase Your Blood Platelet Count:-

  • Eating more leafy greens
  • Eating more fatty fish.
  • Increasing folate consumption.
  • Avoiding alcohol.
  • Eating more citrus.
  • Consuming more iron-rich foods.
  • Avoiding vitamin E and fish oil supplements.

CONTROL MEASURES

Control of mosquito (vector) transmission, development of dengue vaccine, and antiviral drugs constitute future directions with an aim to prevent and treat dengue infection.

Due to the progressing transmission and enhancing 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 control 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.

PREVENTION MEASURES

The proximity of mosquito vector breeding sites to human habitation is a significant risk factor for dengue as well as for other diseases that Aedes mosquito transmit. At present, the main method to control or prevent the transmission of dengue virus is to combat the mosquito vectors. This is achieved through:

  • Prevention of mosquito breeding:
    • Preventing mosquitoes from accessing egg-laying habitats by environmental management and modification.
    • Disposing of solid waste properly and removing artificial man-made habitats that can hold water.
    • Covering, emptying and cleaning of domestic water storage containers on a weekly basis.
    • Applying appropriate insecticides to water storage outdoor containers.
  • Personal protection from mosquito bites:
    • Using of personal household protection measures, such as window screens, repellents, insecticide treated materials, coils and vaporizers. These measures must be observed during the day both inside and outside of the home (e.g.: at work/school) because the primary mosquito vectors bites throughout the day;
    • Wearing clothing that minimises skin exposure to mosquitoes is advised;
  • Community engagement:
    • Educating the community on the risks of mosquito-borne diseases;
    • Engaging with the community to improve participation and mobilization for sustained vector control;
  • Reactive vector control:
    • Emergency vector control measures such as applying insecticides as space spraying during outbreaks may be used by health authorities;
  • Active mosquito and virus surveillance:
    • Active monitoring and surveillance of vector abundance and species composition should be carried out to determine effectiveness of control interventions;
    • Prospectively monitor prevalence of virus in the mosquito population, with active screening of sentinel mosquito collections;