DIAGNÓSTICO Y TRATAMIENTO DE DENGUE, CHIKUNGUNYA Y ZIKA LUIS J. LUGO VÉLEZ M.D. J.D. LL.M. FCLM ASSISTANT PROFESSOR PONCE HEALTH SCIENCES UNIVERSITY SCHOOL OF MEDICINE ADJUNCT FACULTY PONTIFICAL CATHOLIC UNIVERSITY SCHOOL OF LAW

DENGUE THE VIRUS Dengue virus (DEN) is a small single-stranded RNA virus comprising four distinct serotypes (DEN-1 to -4). These closely related serotypes of the dengue virus belong to the genus Flavivirus, family Flaviviridae.

CHIKUNGUNYA Chikungunya virus (CHIKV), an alphavirus in the family Togaviriade, was first discovered in Tanzania in 1953. It is closely related to Ross River Virus, O’Nyong Nyong virus, and Semliki Forest Virus. CHIKV is transmitted in a person-to-mosquito-to-person transmission cycle.

VIRUS DEL ZIKA ARN de cadena simple Género Flavivirus Familia Flaviviridae Estrechamente relacionado a otros virus: Dengue Virus del Nilo Occidental Fiebre amarilla Encefalitis japonesa Primer reporte en 1947, Uganda en el Bosque de Zika (monos)

VÉCTOR COMÚN Principalmente Aedes aegypti y Aedes albopictus. Disperso ampliamente en las Américas, el Caribe y el mundo. Pica agresivamente, en especial durante el día.

AEDES MOSQUITOES Household container breeders Breeds in: clean water In all stored water for drinking, washing and bathing Rainwater collected in unused materials like coconut shells, mud pots, plastic cups, tires etc.

DENGUE Febrile phase Patients typically develop high-grade fever suddenly. This acute febrile phase usually lasts 2–7 days and is often accompanied by facial flushing, skin erythema, generalized body ache, myalgia, arthralgia and headache. Some patients may have sore throat, injected pharynx and conjunctival injection. Anorexia, nausea and vomiting are common. It can be difficult to distinguish dengue clinically from non-dengue febrile diseases in the early febrile phase. A positive tourniquet test in this phase increases the probability of dengue

TOURNIQUET TEST

DENGUE Febrile phase Mild hemorrhagic manifestations like petechiae and mucosal membrane bleeding (e.g. nose and gums) may be seen. Massive vaginal bleeding (in women of childbearing age) and gastrointestinal bleeding may occur during this phase but is not common. The liver is often enlarged and tender after a few days of fever. The earliest abnormality in the full blood count is a progressive decrease in total white cell count, which should alert the physician to a high probability of dengue.

DENGUE Critical Phase Around the time of de-fervescence, when the temperature drops to 37.5–38°C or less and remains below this level, usually on days 3–7 of illness, an increase in capillary permeability in parallel with increasing hematocrit levels may occur. This marks the beginning of the critical phase. The period of clinically significant plasma leakage usually lasts 24–48 hours.

DENGUE Critical Phase Progressive leukopenia followed by a rapid decrease in platelet count usually precedes plasma leakage. At this point patients without an increase in capillary permeability will improve, while those with increased capillary permeability may become worse as a result of lost plasma volume. The degree of increase above the baseline hematocrit often reflects the severity of plasma leakage.

DENGUE Shock occurs when a critical volume of plasma is lost through leakage. It is often preceded by warning signs. The body temperature may be subnormal when shock occurs. With prolonged shock, the consequent organ hypoperfusion results in progressive organ impairment, metabolic acidosis and disseminated intravascular coagulation. This in turn leads to severe hemorrhage causing the hematocrit to decrease in severe shock. Instead of the leukopenia usually seen during this phase of dengue, the total white cell count may increase in patients with severe bleeding.

DENGUE Recovery phase If the patient survives the 24–48 hour critical phase, a gradual reabsorption of extravascular compartment fluid takes place in the following 48–72 hours. General well-being improves, appetite returns, gastrointestinal symptoms abate, haemodynamic status stabilizes and diuresis ensues. The hematocrit stabilizes or may be lower due to the dilutional effect of reabsorbed fluid. White blood cell count usually starts to rise soon after de-fervescence but the recovery of platelet count is typically later than that of white blood cell count.

SEVERE DENGUE Severe dengue is defined by one or more of the following: plasma leakage that may lead to shock (dengue shock) and/or fluid accumulation, with or without respiratory distress, and/or severe bleeding, and/or severe organ impairment.

SEVERE DENGUE Severe dengue should be considered if the patient is from an area of dengue risk presenting with fever of 2–7 days plus any of the following features: There is evidence of plasma leakage such as: – high or progressively rising haematocrit; – 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, un-recordable blood pressure).

SEVERE DENGUE There is significant bleeding. There is an altered level of consciousness (lethargy or restlessness, coma, convulsions). There is severe GI involvement (persistent vomiting, increasing or intense abdominal pain, jaundice). There is severe organ impairment (acute liver failure, acute renal failure, encephalopathy or encephalitis, or other unusual manifestations, cardiomyopathy

DENGUE DIAGNOSIS Laboratory diagnosis methods for confirming dengue virus infection may involve detection of the virus, viral nucleic acid, antigens or antibodies, or a combination of these techniques.

DENGUE TREATMENT Fortunately, this viral disease is usually self-limited and usually adequate hydration and pain control will help the person through the infection. NSAIDs and aspirin should be avoided because of the tendency of the dengue viruses to cause hemorrhages. More severe variations of dengue fever (hemorrhagic and shock syndrome) usually require additional supportive treatments; these patients often require hospitalization. IV hydration, blood transfusions, platelet transfusions, blood pressure support, and other intensive-care measures may need to be utilized in these patients. 

CHIKUNGUNYA Not every person infected with CHIKV exhibits symptoms. It is estimated that 3% to 28% of those infected are asymptomatic. However, these people are still capable of transmitting the disease.

CHIKUNGUNYA: CLINICAL “Dengue  with arthritis” Incubation period: 3‐7 days (range: 2‐12) Symptoms Fever ‐usually ends abruptly after 2 days Arthralgia/arthritis,  insomnia and prostration  ‐last up to a week rash, conjunctivitis, photophobia, fatigue In middle age, joint pains may last 4‐10 weeks,  longer  in elderly Rarely fatal

CHIKUNGUNYA: CLINICAL ARTHRITIS & ARTHRALGIA Painful swelling of the joints tends to occur bilaterally on the extremities. Polyarthralgias and arthritis most commonly occur in joints of the hands, feet, wrists, ankles, elbows or knees. Chikungunya fever often causes arthralgia or arthritis (pain with swelling) that is more severe than that caused by dengue fever.

CHIKUNGUNYA: CLINICAL ARTHRITIS & ARTHRALGIA Neck pain and lower back pain is also more common than with dengue fever. Swelling may be visible and can be a sign of arthritis. Tenosynovitis (inflammation of the sheaths that surround tendons) may also occur. Patients are often bed-ridden and completely incapacitated

CHIKUNGUNYA: ARTHRITIS

CHIKUNGUNYA: CLINICAL One out of two patients will develop a rash. Maculopapular rashes are common and usually develop on the trunk and extremities of the patient. This rash can also appear on the soles, palms, and the face. Another form of the rash called diffuse erythema may occur. If pressure is applied, the rash will blanch. Rashes in chikungunya infections are more common than that of dengue fever.

CHIKUNGUNYA: RASH

CHIKUNGUNYA: CLINICAL Fever usually disappears after 2-3 days. Muscle and joint pain, which can be very severe usually lasts for about 5-7 days but in some cases for much longer periods. Elderly patients in particular may suffer muscle and joint pain for several months.

CHIKUNGUNYA DIAGNOSIS Laboratory diagnosis is generally accomplished by testing serum or plasma to detect virus, viral nucleic acid, or virus-specific immunoglobulin (Ig) M and neutralizing antibodies. 

CHIKUNGUNYA TREATMENT There is no vaccine or specific treatment available against CHIK V infection. Fortunately, the illness is usually self-limiting and resolves with time. Supportive therapy with antipyretics are used to control fever and joint pain.

Zika 1 de cada 5 (20%) personas infectadas desarrollan síntomas Afecta todos los grupos de edad Rara vez enfermedad severa, hospitalizaciones, o muerte Periodo de incubación usualmente 3–12 días Síntomas típicamente duran 2-7 días

ZIKA CICLO PRIMARIO DE TRANSMISIÓN Transmisión antroponótica persona a mosquito a persona Otras modalidades de transmisión de Zika Materno -fetal Intra-uterino Perinatal Contacto sexual: hombre-mujer Transfusión de sangre Exposición laboratorio No hay evidencia de transmisión Trasplante de órganos o tejido Lactancia Saliva Orina

SIGNOS Y SÍNTOMAS Síntomas más comunes Fiebre Rash (maculopapular) Conjuntivitis (no purulenta) Cefalea (dolor de cabeza) Artralgia Edema en extremidades

MANEJO CLÍNICO No hay terapia antiviral específica Hidratación y estabilidad hemodinámica Otras condiciones que pudiesen comprometer el tratamiento o manejo del caso Muestras para diagnóstico Manejar como dengue hasta descartar la posibilidad de infección por dengue Reduce riesgo de enfermedad severa y muerte NO usar aspirina y anti-inflamatorios no esteroidales (NSAIDs), aumentan el riesgo de hemorragias en pacientes con dengue

DESPUÉS DE UNA INFECCIÓN CON ZIKA Inmunidad de por vida Conocimiento limitado sobre secuela tras infección Defectos congénitos: Microcefalia Guillian-Barré

EXPANSIÓN DEL ZIKA 2007-2015 • 2007, brote en Isla de Yap, en Micronesia Tasa de ataque en la población 73% 2013–2014, >28,000 casos en Polinesia Francesa Otras Islas del Pacifico y Oceanía

MEDIDAS PREVENTIVAS No existe vacuna o medicamento Prevención primaria es reducir la exposición a mosquitos Evitar la picadura del mosquito en personas infectadas, particularmente la primera semana de enfermedad Uso de condones, particularmente parejas de mujeres embarazadas (todo el embarazo)

PREVENCIÓN Y CONTROL DEL MOSQUITO Vacíe o elimine los contenedores que acumulan agua Use aire acondicionado o tela metálica en puertas y ventanas Use repelentes de mosquito en la piel expuesta Use ropa de manga y pantalón largo Apoye los esfuerzos de los programas de control de mosquitos

Casos confirmados de CHIKV, DENV, y ZIKA, 2016 — 2017 Acumulado en 2016 70,957 presuntos Casos confirmados: DENV : 170 casos CHIKV: 178 casos ZIKV: 38,116 casos Acumulados de ZIKV 2016–2017 38,461 casos confirmados 3,050 mujeres embarazadas 1,755 (58%) sintomáticoS 1,295 (42%) asintomáticos 382 (<1%) hospitalizados Semanas 1 — 4, 2017 1,844 presuntos Casos confirmados: DENV : 1 casos CHIKV : 1 casos ZIKV : 345 casos