Dengue Fever PDF

MICROBIOLOGY AND PARASITOLOGY DENGUE FEVER Maria Christina S. Padilla, MD | September 25, 2024 Once infectious, the mosquito can transmit the virus for...

MICROBIOLOGY AND PARASITOLOGY DENGUE FEVER Maria Christina S. Padilla, MD | September 25, 2024 Once infectious, the mosquito can transmit the virus for EPIDEMIOLOGY the rest of his life. Global: → 200 million Dengue cases → 500 Dengue related deaths As of March, 2024 → Philippines: 5,000 cases, 7 deaths Philippines logs 208,000 dengue cases as of Sept 2024 Peak during rainy season (July to August) CAUSATIVE AGENT Dengue virus → Flaviviridae family → Enveloped, positive-sense, single-stranded RNA virus with icosahedral nucleocapsid → Arbovirus (Arthropod-borne virus) → 4 serotypes: ▪ DENV-1 ▪ DENV-2 ▪ DENV-3 ▪ DENV-4 → DENV-5: 5th variant ▪ Discovered in October 2013 Doc Tina: ▪ Follows the Sylvatic cycle of primates Proboscis of the mosquito have anticoagulant (the anticoagulant in the saliva prevents blood from clotting, allowing the mosquito to draw blood more efficiently) DENGUE SEROTYPES Extrinsic incubation (found in mosquito only): usually 8-10 days “so kapag kumagat ang mosquito bago lang sa infected human Each serotype provides specific lifetime immunity and with dengue ngayong araw lang, pag kinagat ka, di pa ma short-term cross immunity to other serotypes transfer ang virus. It needs to be incubated 8-10 days).” - Dra. Genetic variation within serotypes Padilla → Some genetic variants appear to be more virulent and After the incubation period, the mosquito can transmit the virus to may have greater or lesser potential to cause UNinfected human. epidemics The incubation period for dengue typically ranges from 4 to 7 DENV-1 and DENV-3: More pathogenic without immune days after the bite of an infected mosquito. priming from other serotypes DENV-4: causes more mild disease in primary DENV infections DENV-2 and DENV-3: more likely to cause DHF as DENGUE FEVER PATHOGENESIS secondary infections than DENV-4 1. Fusion o Viral envelope glycoprotein important for VECTOR effectivity o Bind to viral receptors. Aedes aegypti 2. Disassembly (the release of the virus or uncoating) → Primary vector - Urban dengue 3. Viral replication → Main tiger mosquitoes because they have 5 broad 4. Viral Assembly white bands on hind pair of legs 5. Maturation and Release → They mesonotum have a lyre shaped silvery marking Aedes albopictus → Secondary vector - Rural dengue → Asian tiger mosquito (Forest tiger mosquito) have a single, longitudinal silvery marking on mesonotum, Low flier TRANSMISSION Human-Mosquito-Human Transmission Through bites of an infected FEMALE Aedes species mosquito Day time biting → Highest: usually 2 hours after sunrise and before sunset Transcribed by: NMD 2027  Specimen Collection Infection with unencountered DENV serotypes CLINICAL MANIFESTATIONS Classical Dengue fever CLASSIC DENGUE FEVER May lead to Dengue Hemorrhagic Fever and Dengue Shock Syndrome Saddleback/biphasic fever (40C) Increase in viral load and severity of disease - ADE → 2-7 days (range, 3-14 days). The temperature may (Antibody-dependent Enhancement) phenomenon subside on the 3rd day and rise again about 5-8 days after onset Antibody-Dependent Enhancement (ADE) Phenomenon Pathophysiology: The antibodies from the primary infection cannot neutralize the second serotype.The Ab-virus complex attaches to Fc receptors on circulating monocytes leading to more efficient infection of monocytes and macrophages. Unchecked viral replication with higher viral titers and increased cytokines production and complement activation. Incubation period: 3-7 days (up to 14 days) Signs and symptoms: → Breakbone fever (characteristic of deep bone pain and myalgia) → Severe headache → Retroorbital pain → Nausea and vomiting → Facial flushing/Rash - maculopapular or macular confluence over the face, thorax and flexor surfaces, with islands of skin sparing “white islands in a sea of red” HERMAN’S RASH (becomes prominent during the CONVALESCENT OR RECOVERY PHASE → Positive(+) Tourniquet set ▪ take the patient’s blood pressure and record e.g. 120/80 ▪ add Systolic and Diastolic. Get the average (120 + 80 = 200) average is 100 ▪ inflate the cuff to 100 mmHg, let it stay for 5 minutes ▪ deflate Example: at first exposure to serotype 1, the Bcell in the body will ▪ then measure in the antecubital fossa promote the production of antibody specifically for serotype 1. If you’re ▪ look for small red spots (petechiae) within a 1-inch exposed to serotype 1 for the second time, the virus will just be square area. neutralized by the antibody. However, if you are exposed to another ▪ count how many petechiae inside the square serotypes (2,3, or 4), the antibody will bind but it cannot neutralize the ▪ (+) more than 10 petechiae virus. “Instead, it will promote the tagging of the virion antibody to that of ▪ if more than 20 petechiae, patient is prone to the cell through FC gamma receptor. Papasok ang virion sa katawan, bleeding mag iincrease yung viral load mo, diyan papasok yung lahat ng severe symptoms hanggang sa pwede ka magkaroon ng hemorrhagic or shock syndrome.” SEVERE DENGUE If the patient is from an area of dengue risk presenting with fever of 2-7 days There is evidence of plasma leakage: → high or progressively rising hematocrit; → pleural effusions or ascites; → circulatory compromise or shock (tachycardia, cold and clammy extremities, capillary refill time greater than three seconds, weak or undetectable pulse, narrow pulse pressure or, in late shock, unrecordable blood pressure) Doc Tina: because of cytokine storm (the release of different cytokines),vascular permeability is increased causing plasma leakage There is significant bleeding There is an altered level of consciousness (lethargy or restlessness, coma, convulsions) There is severe gastrointestinal involvement (persistent PRIMARY DENGUE INFECTION vomiting, increasing or intense abdominal pain, jaundice) First exposure to any of DENV serotypes There is severe organ impairment (acute liver failure, Patient may be asymptomatic acute renal failure, encephalopathy or encephalitis, or IgM (3-5 days); transient (M - morning, thus 1st to appear) other unusual manifestations, cardiomyopathy) or other IgG (6-10 days); persists for life (G- gabi, last to appear) unusual manifestations Provide lifelong immunity against that particular serotype Transient or short term cross immunity to other serotypes Doc Tina: and pag kinapa mo yung liver, enlarged siya (“Hepatomegaly”). Isa sa mga lab request should be LIVER ENZYMES (SGOT & SGPT) SECONDARY DENGUE INFECTION 2 of 7  Specimen Collection WHO CLASSIFICATION OF DENGUE DENGUE +/- WARNING SIGNS PROBABLE Live in/travel to dengue endemic area DENGUE Fever and two of the following criteria: ○ Nausea ○ Vomiting ○ Rash ○ Aches and Pains ○ Tourniquet test (+) ○ Leukopenia (decreased WBC) - first indication for change ○ Any warning sign Laboratory-confirmed dengue; (Important when no sign of plasma leakage) WARNING Any one of the symptoms: SIGNS ○ Abdominal pain or tenderness ○ Persistent vomiting ○ Clinical fluid accumulation ○ Mucosal bleed ○ Lethargy, restlessness ○ Liver enlargement >2cm Laboratory: Increase in HCT concurrent with rapid decrease in platelet count (Needs strict observation and medical intervention) SEVERE DENGUE Severe plasma leakage leading to: ○ Shock (Dengue Shock Syndrome) ○ Fluid accumulation with respiratory distress Severe bleeding (as evaluated by clinician) Severe organ involvement ○ Liver: AST or ALT >/= 1000 ○ CNS: Impaired consciousness ○ Heart and other organs TOURNIQUET TEST REVISED WHO DENGUE CASE CLASSIFICATION Also known as “Capillary fragility test” → A clinical diagnostic method to determine a patient's hemorrhagic tendency. → It used to identify thrombocytopenia → More positive at the time of defervescence; → Less to be positive in shock RESULTS: → (+) if ≥10 petechiae per 2.5 cm2 (1 inch2 ) → Using a cut off of ≥20 petechiae/square inch increases specificity, but loses sensitivity Doc Tina: For dengue without warning signs, in your history, you should first ask ‘saan ka nakatira?’ and ‘nagtravel ka ba?’. This is because if the DENGUE HEMORRHAGIC FEVER patient has no travel history and the place is not endemic to dengue “Dengue Viral Illness with Warning Signs” then it's most probably not dengue. Biphasic Fever or recent history of fever lasting 2–7 days Any hemorrhagic manifestation: ▪ Epistaxis 3 of 7  Specimen Collection ▪ Gingival bleeding temperature drops then it may be an indication that you are in the ▪ Bleeding from injection sites critical phase. Laboratory tests should also be checked ▪ Positive tourniquet test (thrombocytopenia and hemoconcentration). ▪ Petechiae, purpura, or hematomas on skin ▪ Abdominal pain tenderness NS1 antigen (Nonstructural protein 1) - to check for the height of dengue virus ▪ Persistent vomiting typically requested in the febrile phase (high viremia) ▪ Clinical fluid accumulation should be requested until day 7 only (on the 5th day there ▪ Lethargy, restlessness are already immunoglobulins) ▪ Liver enlargement >2cm day 8 onwards, better request for dengue IgG/IgM ▪ Increased Hematocrit with decrease platelet Thrombocytopenia (platelet count of