dengue who guideline 2009

DENGUEREVISED WHO GUIDELINE FOR DIAGNOSIS,

TREATMENT, PREVENTION AND CONTROL,

2009

Updates 2016Dr. Aijaz SoomroResident FCPSMU II, Civil Hospital LarkanaMonday November 21, 2016

Objectives of Presentation• Introduction to Dengue virus & its Vector

• Dengue Epidemiology

• Risk Factors

• WHO case classification of Dengue

• Clinical Phases of Dengue Illness

• Differential Diagnoses

• Diagnosis of Dengue

• Complications of Dengue

• Stepwise Management of Dengue

• Dengue Prevention & Control

• Methods of Vector Control

• Dengue Vaccine WHO Position Paper, July 2016

Dengue Viral Infection

• The most rapidly spreading mosquito-borne viral disease in the world.

• Dengue Virus:Family: FlavivirdaeGenus:FlavivirusSingle stranded RNA virusIncubation period: 4 – 10 days (can be 3 – 15 days)

4 Serotypes: DEN1, DEN2, DEN3, DEN45th serotype?

• Asian Genotypes: DEN2, DEN3 are often associated with severe disease accompanying secondary dengue infections.

VectorAedes Aegypti (Stegomyia Aegypti) (Main Vector)

Aedes Albopictus (Less common)

Anopheles vs. Aedes

Dengue Epidemiology70-500 million dengue infections annually

2.5 billion people at risk

Average annual number of DF and DHF cases reported to WHO, 1955 - 2007

Burden of Disease

Risk Factors Risk factors determine the severity of disease and secondary infection

• Age: Infants, elderly

• Ethnicity: Black people immune to severe dengue compared to white, White people show stronger cross protective immunity.

• Co-morbidity such as Bronchial Asthma, Sickle cell anemia, Diabetes Mellitus.

• Young children: Especially young girls. Less able to compensate for capillary leakage and are consequently at greater risk of dengue shock

• Secondary heterotypic infection: Antibody Dependent Enhancement. Non-neutralizing antibodies make host more susceptible to infection.

Dengue Case Classification“Dengue is one disease entity with different clinical presentations and

often with unpredictable clinical evolution and outcome”.

• Asymptomatic (~75%)

• Symptomatic (~25%) 1. Undifferentiated Fever2. Dengue Fever (DF) (~99%)3. Dengue Hemorrhagic Fever

(DHF) (~1%)4. Dengue Shock Syndrome

(DSS)

Clinical FindingsUsually a nonspecific, self-limited Biphasic febrile illness. More than half of infected children are asymptomatic. The illness is more severe and begins more suddenly in adults. After an incubation period of 4–5 days, there is a sudden onset of high fever, chills, and “break bone” aching of the head, back, and extremities accompanied by sore throat, prostration, and malaise. There may be conjunctival redness. Initially, the skin appears flushed or blotched, but 3–4 days after the lysis of the fever, a maculopapular rash, which spares palms and soles, appears in over 50% of cases. As the rash fades, localized clusters of petechiae on the extensor surface of the limbs become apparent.

Dengue Case ClassificationDengue Fever

Dengue Hemorrhagic Fever4 criteria:

1. Recent history of Acute Fever2. Hemorrhagic manifestations3. Low Platelet Count (100,000/mm3 or less)

4. Objective Evidence of Leaky Capillaries elevated hematocrit (20% or more over baseline) pleural or other effusions Fall in HCT >20% after IV fluids

Dengue Case Classification

WHO Dengue Case Classification

Dengue Hemorrhagic FeverFour GradesDF/DHF

Grade Symptoms Laboratory

DF Fever with two or more of the following:HeadacheRetro-orbital painMyalgiaArthralgia

Leucopenia, occasionally thrombocytopenia may be present. No evidence of plasma loss

DHF I Above signs plus Positive tourniquet sign Thrombocytopenia <100,000/mm3; HCT rise >20%

DHF II Above signs plus spontaneous bleeding Thrombocytopenia <100,000/mm3; HCT rise >20%

DHF III Above signs plus circulatory failure Thrombocytopenia <100,000/mm3; HCT rise >20%

DHF IV Profound shock with undetectable BP & Pulse Thrombocytopenia <100,000/mm3; HCT rise >20%

Dengue Shock Syndrome

Evidence of circulatory failure manifested indirectly by

Rapid & weak pulse Narrow pulse pressure (<20mmHg) or Hypotension for age Cold & clammy skin Altered mental status

Frank shock is direct evidence of circulatory failure

Dengue Case Classification

Classification by Severity

Clinical Phases of Dengue Illness

Febrile Phase• High grade fever, 2–7 days• Nausea, vomiting, headache, myalgia, arthralgia, body

ache, Fascial flushing, skin erythema, etc.• Indistinguishable between severe and non-severe dengue

cases• Monitoring for warning signs• Mild hemorrhagic manifestation: Petechiae and mucosal

membrane bleeding (Nose and gum Bleeding)• Liver often enlarged and tender after a few days of fever• The earliest abnormality in CBC: Progressive decrease in

WBCs

Clinical Course of Dengue Illness

Critical Phase

• Day 3-7 of illness• Progressive Leucopenia leading to rapid decline in platelet

count and plasma leakage• Patients without capillary permeability will improve• Patients with increased capillary permeability deteriorate by

losing plasma volume• The degree of increase in HCT above baseline reflects

severity of plasma leakage• In Shock, WBCs may increase in patients with severe

bleeding

Clinical Course of Dengue Illness

Recovery Phase

• Gradual reabsorption of extravascular compartment fluid takes place in the following 48 to 72 hours

• Well-being improves appetite returns, GI symptoms abate, Hemodynamic status stabilizes and diuresis ensues

• Rash: ‘Islets of white in the sea of red’. Some may experience generalized pruritus

• HCT stabilizes or lowers due to the dilutional effect of the reabsorbed fluid.

• WBCs usually rise soon after defervescence but the recovery of platelet count is typically later than that of WBCs

Febrile, Critical & Recovery Phases of Dengue and Issues

Phase Issues

Febrile phase Dehydration; High fever may cause neurological disturbance and febrile seizures in young children

Critical phase Shock from plasma leakage; severe hemorrhage; organ impairment

Recovery Phase Hypervolemia develops only if IV fluids therapy has been excessive and /or has been extended into this period

Severe Dengue

• Fever of 2-7 days plus any of the following Evidence of Plasma Leakage: High or progressively rising HCT Pleural Effusions or ascites Circulatory compromise or shock (Tachycardia, cold & clammy extremities, capillary refill time

> 3 sec, weak or undetectable pulse, narrow pulse pressure or in late shock unrecordable BP )

Significant Bleeding Altered level of consciousness (Lethargy or restlessness, coma, convulsions)

Severe GI involvement (persistent vomiting, increasing or intense abdominal pain, jaundice)

Severe organ impairment (acute liver failure, ARF, encephalopathy or encephalitis, or other usual manifestations, cardiomyopathy)

Dengue – Primary Infection

• NS1 Antigen: Day 1 after onset of fever and up to days 9• IgM antibody:

* Day 5 of infection, sometimes as early as Day 3 * IgM level : Peaks in 2 weeks, followed by a 2 week rapid decay * Undetectable 2 to 3 months after infection

• Low levels of IgM are detected in early convalescent phase not during the acute phase

• Anti-dengue serum IgG is generally detectable at low titers at the end of the first week of illness, increasing slowly thereafter, with serum IgG still detectable after several months, and probably even for life.

Dengue – Secondary Infection• NS1 antigen: Day 1 after onset of fever and up to day 9.• IgM response in more varied, usually preceded by IgG and appears

quite late during the febrile phase.• IgM may not be produced until 20 days after onset of infection.• Antibody titers rise rapidly and react broadly against many

flaviviruses.• The dominant immunoglobulin is IgG isotype which is detectable at

high levels, even in the acute phase, and persists for periods lasting from 10 months to life.

• Raised IgG in acute phase and 4-fold rise in IgG in convalescent phase confirms Secondary infection.

• Early convalescent stage IgM levels are significantly lower in secondary infections than in primary ones and may be undetectable in some cases.

• To distinguish primary and secondary dengue infections, IgM/IgG antibody ratios ( ≥ 1.14 cut off point).

Differential Diagnosis of Dengue

Diagnosis of Dengue Infection• Antibody detection Hemagglutination inhibition (HAI) ELISA (IgG/IgM) Rapid test (IgG/IgM)

• Antigen detection NS1 & E/M antigen

• RNA detection PCR

• Viral isolation

Diagnosis of Dengue Infection

Interpretation of Dengue Diagnostic Tests

Gastrointestinal: Hepatitis, Fulminant Hepatic Failure, GI bleeding, Acalculous Cholecystitis, Acute Pancreatitis

Renal: Acute Kidney Injury, Acute Renal Failure, Proteinuria, Glomerulonephritis

Respiratory: ARDS, Pneumonia, Pulmonary Hemorrhages

Lymphoreticular: Bone Marrow failure, Aplastic anemia, Splenic rupture, Lymph node Infarction, Hemophagocytosis

Cardiovascular: Rhythm disorders (AV block, AF, Sinus node dysfunction, Ectopic ventricular beats), Viral Myocarditis

Musculoskeletal: Acute benign myositis, Persistent severe myositis

Neurologic: Encephalitis, GB syndrome, Phrenic neuropathy, Subdural hematoma, Transverse Myelitis, Stroke

Ophthalmic: Retinal hemorrhage, Iritis, Maculopathy

Obstetric: Premature birth, Hemorrhage

Others: Depression & Chronic Fatigue, Bacterial Superinfections

Complications of Dengue

Immunity against Dengue Infection

• Primary Infection induces lifelong protective immunity to the infecting serotype.

• Individual suffering an infection are protected from clinical illness with a different serotype within 2-3 months of the primary infection.

• No long-term cross immunity. Secondary infections with other serotypes can occur.

Management of Dengue Infection

A stepwise approach to the management of Dengue

Management of Dengue

Group A patients who are sent Home

• Encourage plenty of oral Fluids• Inform about the warning signs• Paracetamol for high fever • Never Aspirin, Ibuprofen, or other NSAIDs

Admission Criteria For Group B & C Patients

Group BIn-patient Hospital Management

• Obtain Baseline Hematocrit• Give only isotonic solution• Reassessment and repeat hematocrit• IV fluids usually required for 24 – 48 hours

Fluid management in Compensated Shock for Group C Patients

Fluid management in Hypotensive Shock for Group C Patients

Treatment of Hemorrhagic Complications

• Mucosal Bleeding: If patient remains stable with fluid resuscitation/replacement, consider as minor

• Patient with profound thrombocytopenia: Strict bed rest and protect from trauma, not give IM injection (avoid hematoma),

• In hemodynamically stable patients prophylactic platelet transfusions for severe thrombocytopenia have not been shown to be effective and not necessary.

• In hemodynamically unstable patients, give 5–10ml/kg of fresh packed red cells or 10–20 ml/kg of fresh whole blood at an appropriate rate and observe the clinical response. Repeat if further blood loss.

• Bleeding improves rapidly during recovery phase

Dengue Prevention & Control

Preventing or reducing dengue virus transmission depends entirely on1. Control of the mosquito vectorsControl Ae. aegypti (the main vector), Aedes Albopictus or others in the habitats of its immature and adult stages in the household and immediate vicinity. Typically, these mosquitoes do not fly far, the majority remaining within 100 meters of where they emerged. They feed almost entirely on humans, mainly during daylight hours, and both indoors and outdoors.

2. Interruption of human–vector contactTake measures at houses, schools, hospitals and workplaces.Purposely-filled household containers such as those used for domestic water storage and for decorative plants should be removed.Rain-filled habitats – including used tyres, discarded food and beverage containers, blocked gutters and buildings under construction should be managed properly.

Integrated Vector Management (IVM) refers to “a rational decision-making process for the optimal use of resources for vector control”.

IVM includes Advocacy, social mobilization and legislation, Collaboration within the health sector and with other sectors, Integrated approach to disease control, Evidence-based decision-making, capacity-building.

Overview

Methods of vector control include the elimination or management of larval habitats, larviciding with insecticides, the use of biological agents and the application of adulticides.

1. Environmental ManagementEnvironmental modification such as piped water supply. Environmental manipulation: by temporary changes to vector habitats involving the management of “essential” containers, such as frequent emptying and cleaning by scrubbing of water-storage vessels, flower vases and desert room coolers; cleaning of gutters; sheltering stored tyres from rainfall; recycling or proper disposal of discarded containers and tyres; management or removal from the vicinity of homes of plants such as ornamental that collect water in the leaf axils.Changes to human habitation or behaviour: actions to reduce human–vector contact, such as installing mosquito screening on windows, doors and other entry points, and using mosquito nets while sleeping during daytime.

Methods of Vector Control

2. Chemical control: larvicidesAlthough chemicals are widely used to treat Ae. aegypti larval habitats, larviciding should be considered as complementary to environmental management and – except in emergencies – should be restricted to containers that cannot otherwise be eliminated or managed.• Organophosphates• Insect Growth regulators• Biopesticies

3. Chemical control: adulticidesMethods of chemical control that target adult vectors are intended to impact on mosquitodensities, longevity and other transmission parameters.• Organophosphates• Pyrethroids

Methods of Vector Control

4. Safe use of insecticidesAll pesticides are toxic to some degree. Safety precautions for their use – including care in the handling of pesticides, safe work practices for those who apply them, and appropriate field application – should be followed.

5. Monitoring of insecticide susceptibilityInsecticide resistance must be considered as a potentially serious threat to effective dengue vector control. Routine monitoring of insecticide susceptibility should be integral to any programme.

6. Individual and household protectionClothing that minimizes skin exposure during daylight hours during outbreaks. Repellents may be applied to exposed skin or to clothing. Repellents should contain DEET, IR3535 or Icaridin.Insecticide-treated mosquito nets afford good protection for those who sleep during the day (e.g. infants, the bedridden and night-shift workers).Where indoor biting occurs, household insecticide aerosol products, mosquito coils or other insecticide vaporizers may also reduce biting activity. Household fixtures such as window & door screens and air-conditioning can also reduce biting.

Methods of Vector Control

7. Biological controlBiological control is based on the introduction of organisms that prey upon, parasitize, compete with or otherwise reduce populations of the target species.• Larvivorous fish• Predatory copepods• Freshwater crustaceans have benn proven to be effective against Aedes mosquitoes

8. Towards improved tools for vector control• Insecticide-treated materials• Lethal ovitraps: device which consists of a black cylinder with a piece of cardboard submerged into the water in the cup.Ovitraps mimic the preferred breeding site for containerbreeding mosquitoes, including Aedes albopictus and Aedes aegypti.

Methods of Vector Control

Dengue vaccineWHO Position Paper – July 2016

Vaccines• (CYD-TDV, or Dengvaxia®); this is a live attenuated (recombinant)

tetravalent vaccine.• Several other dengue vaccine candidates are in clinical development.

Vaccine characteristics• CYD-TDV is a prophylactic, tetravalent, live attenuated viral vaccine. • Schedule: 3 injections of 0.5 mL administered at 6-month intervals

(0, 6, 12).• Vaccine works against virus serotypes 1, 2, 3, and 4 in individuals 9–

45 years or 9–60 years of age (depending on the license), people living in dengue endemic areas.

• The lower limit of the indication at 9 years of age was chosen due to a safety concerns in children aged 2–5 years.

Vaccine Availability

“In 2016 a partially effective vaccine for dengue fever (Dengvaxia®) became commercially available in the Philippines and Indonesia. It has also been approved by Mexico, Brazil, El Salvador, Costa Rica, and Paraguay. In Indonesia it costs about US$ 207 for the recommended three doses.”

Wikipedia

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