Pedia 2.2b Dengue - Dra Bibera

2.2b DENGUE

PEDIATRICS II

Dra. Bibera | August 1, 2014 OUTLINE I. Dengue A. Dengue Fever B. Vector II. Risk Factors for Dengue Hemorrhagic Fever (DHF) III. Hypothesis on the Pathgenesis of DHF A. Homologous Antibodies B. Heterologous Antibodies C. Clinical Case Definition for Dengue Hemorrhagic Fever IV. Clinical Case Definition for Dengue Shock Syndrome IV. Key and changing facs in Dengue V. Updated Clinical Management Guidelines A. Step 1: Overall Assessment B. Step 2: Diagnosis, Assessment of Disease Phase and Severity C. Management Disease Notification VI. Management Decisions A. Group A: Patients who may be sent Home B. Group B: Patient who Should be Referred for Hospitalization C. Group C: Patients with Severe Dengue who Require Emergency treatment and Urgent Referral VII. Summary References: PPT, Recording, Old Trans Legend: Italicized – recording bold – emphasized by  – 2015 trans

A. DENGUE ● “Dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome” ● Transmitted by Aedes aegypti mosquito

Figure 1. Areas at risk for Dengue

● Approximately 2.5 billion people live in dengue endemic areas and 50 M infections occur annually ● More than 75% live in southeast asia and western pacific regions

A. DENGUE VIRUS ● Causes dengue and dengue hemorrhagic fever ● Is an arbovirus  It is a flavivirus, from the family flaviviridae. Most of the viruses from this family are arboviruses. ● Transmitted by infected FEMALE mosquitoes

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● Has 4 serotypes (DEN 1,2,3,4)- Each serotype provides specific lifetime immunity, and short term cross-term immunity which can cause severe and fatal disease ● DEN-1 and DEN-2: most common isolated serotypes in the Philippines, but we have all 4 types. ● Causes partial and transient protection against subsequent infections by the other serotypes  If you have dengue now, you have protection from all other types for the next 6 months. After 6 months, you are again prone to have your next dengue episode. ● Some genetic variants within each serotype appear to be more virulent or have greater epidemic potential.

B. VECTOR ● FEMALE Aedes aegypti ● Other vectors: A. albopictus (gaining strength recently), A. polysiensis, A. scutellaris ○ Dra. Bibera: Sadly, we have all other vectors, most commonly A. albopictus. Aegypti is a very sociable mosquito. ○ The males are the weaker sex, because once they have mated with the female mosquito, they die while the female mosquito reigns and becomes the queen ● Primarily a DAYTIME feeder ● very sociable; lives around human habitation ● Transmission sites: communities and schools ● Common in urbanized municipalities ○ This is not true anymore, as it is already common even in the rural areas ● Lays eggs and produces larvae preferentially in artificial containers ● Based on the study “Entomological Survey in Selected Public Hospitals in Metro Manila”: Containers found positive for A. aegypti larvae: ○ Flower vases in accounting office ○ Nursing office ○ Urology ward ○ Basin in OB ward ○ Plastic cups in hallway ● Flight range: 20% following volume replacement ● Low albumin ● Pleuralor other effusions because you have a lot of fluids getting out of the BV into the 3rd space ● Leaky capillaries – Leakage of fluid because of capillary permeability. This is the main pathophysiologic mechanism that sets it apart from Dengue Fever that’s why we don't look at platelet count, we look at ELEVATED HCT because fluid/plasma leaks out of the BV so you will have your elevated Hct even in situations wherein you will have volume replacement or even pushing a lot of IV fluids that Hct will go up, then you’re dealing with DHF. ● Very difficult to diagnose DHF because you have to fulfill all 4 necessary criteria

4 criteria for DHF + CIRCULATORY FAILURE manifested indirectly by all of the following: ● Rapid and weak pulse (Check the Dorsalis Pedis pulse since this will be affected first) ● Narrow pulse pressure (≤ 20 mmHg) OR hypotension for age (< 80 mmHg systolic < 5 yrs and 90 mmHg systolic > 5 yrs) Narrow pulse pressure of ≤ 20 mmHg difference of systolic and diastolic, so even if you have a normal systolic pressure,(e.g. 120/100) but has narrow pulse pressure, then that’s a warning sign of shock. ● Cold, clammy skin and altered mental status ● Frank shock is direct evidence of circulatory failure

FROM 2015 TRANS A. CLINICAL COURSE OF DSS ● Usually occurs between D3-D7 of illness ● Critical period 24-48 hours ● Adequate urine output and return of appetite-good prognostic signs ● Prolonged shock and metabolic acidosis-poor prognostic signs (precipitate occurrence or enhance DIC->massive bleeding) ● If no treatment, dies within 12-24 hours after shock ensues ● Recovery from shock is 2-3 days ● Common findings in convalescence: sinus bradychardia and arrhythmia ● Characteristic confluent petecchial rash with small round areas of normal skin

B. UNUSUAL MANIFESTATIONS OF DSS  

CNS involvement oEncephalitis oEncephalopathy Hepatic Involvement oJaundice oLiver Failure with hepatic encephalopathy oIncrease liver enzymes Page 3 of 10

PEDIATRICS II 2.2b

B. NIGHT-BITING AEDES MOSQUITO C. LABORATORY DIAGNOSIS    

Thrombocytopenia Hemoconcentration Leukopenia Lymphocytosis with 15-20% atypical lymphocytes 1-2 days before defervescence  Hemostatic abnormalities: oProlonged PTT; decreased fibrinogen, decreased clotting factors, increased fibrin split products  Other tests: oElevated liver enzymes oHyponatremia oIncreased BUN and creatinine oLow Albumin D. LABORATORY CONFIRMATION  Serologic examination  Hemagglutination Inhibition test oMost widely used o4 fold or greater rise in inhibiting antibody titre in paired sera oTitre of 1:1280  Dengue ELISA oNewer test oDetection of specific IgM or IgG antibodies oRequires only single blood samples  Dengue IgM capture (MAC-ELISA) oSimple and rapid test oPrimary Infection: IgMAb positive: Day 5 oIgM antibody significantly higher in primary than in osecondary dengue  Dengue NS1 test: Day 1-4  Virological confirmation: oIsolation of dengue virus from serum or autopsy samples  Confirmation of all dengue virus by immunofluourescence oDemonstration of dengue virus by PCR oSample preferably obtained 3-5 days after onset of fever

IV. KEY AND CHANGING FACTS IN DENGUE ● Primarily an urban disease, now spreading to rural areas worldwide ● Co-circulation with multiple serotypes are common ● Imported cases are common

DOH ON ALERT FOR TOUGHER DENGUE- CARRYING MOSQUITO A. TOUGHER AEDES 

Behavior changes in Aedes cause for whole year round activity. o Reports about "evolved" breeds of mosquitoes that lay their eggs even in polluted water in Peru. o They can breed even in dirty environments like septic tanks.  Before: loves to breed only in artificial containers, now it can breed anywhere. Also, it doesn't need rainfall anymore for dengue. We can have dengue during summer months, it only peaks during rainy season.  In the Philippines, there is a possibility that local mosquitoes may have also evolved and are now breeding even in areas without "clean" water.

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Philippine Association of Entomologists reported a study conducted last year regarding Aedes albopictus: o Daytime and night time feeder (biting time is extended from 6-8pm and 11pm to 1 am) o Natural habitat is in the forested area of Mount Makiling.

SUGGESTED DENGUE CASE CLASSIFICATION AND LEVELS OF SEVERITY (WHO 2009) (APPENDIX 1 and 2) REVISED DENGUE CLASSIFICATION (DOH 2011) PHILIPPINIZED VERSION  

Added: flushed skin Warning signs: decreased or no urine output with 6 hours

CLINICAL PROBLEMS ENCOUNTERED DURING THE DIFFERENT PHASES OF DENGUE Table 1. Phases of Dengue

1 Febrile phase

a. Dehydration; b. High fever may cause neurological disturbances and febrile seizures in young children

2 Critical phase

Shock from plasma leakage; Severe hemorrhage; Organ impairment

Fluid replacement is the cornerstone of treatment Encourage oral intake of oral rehydration solution (ORS), fruit juice and other fluids containing electrolytes and sugar to replace losses from fever and vomiting

3 Recovery Hypervolaemia ( only in phase excessive IVF therapy) associated with pulmonary edema or CHF •

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Rehydrating oral fluids: o Oral rehydration solution o Fruit juice o Rice water Adequate oral fluid intake may be able to reduce the number of hospitalizations o In a hospital and health centre-based study in Nicaragua, fluid intake during the 24 hours before being seen by a clinician was statistically associated with decreased risk for hospitalization of dengue fever patients . o Similar results were obtained for children 3-10 kg 100 cc/kg >10-20 kg 75 >20-30 kg 50-60 >30-60 kg 40-50 o Level of Evidence: Class 3 Grade A RECOMMENDATION #2: Sports drinks should NOT be used in children. o Level of Evidence: Class 3 Grade A B. What anti-pyretic is safe to give in a child with dengue fever? Dengue Fever o endemic in the country; occurs whole year round o always part of the differential diagnosis of fever especially those presenting with influenza-like illness o Paracetamol is the recommended medicine for fever by WHO o Aspirin, mefenamic acid, ibuprofen and other NSAIDs are NOT recommended Things to realize in giving medications for dengue o The goal of treatment is NOT to increase the platelet count. o Treatment should be geared towards decreasing plasma leakage which is the main pathophysiology of dengue

Blood pressure

Normal blood pressure for age. Normal pulse pressure for age.

Normal systolic pressure but rising diastolic pressure.

Postural hypotension Narrowed pulse pressure (