Dengue, Chikungunya and Zika Virus Infection: Answers to Common Questions Wayne Ghesquiere MD FRCPC Infectious Diseases Consultant Clinical Assistant Prof, UBC Victoria, BC Objectives Discuss common Arbovirus infections Dengue Chikungunya Japanese Encephalitis Zika Virus Case presentations Learn some medicine Have fun Case 1 62 year male returns from Puerto Vallarta, Mexico where he been on vacation for 3 weeks Two days prior to leaving he has fatigue and fever He returned home 5 days ago, now he has headaches, rash on his trunk and extremities, His major complaint is muscle pains Dengue Introduction Dengue is also known as Breakbone fever Mortality is 1-5% without treatment With adequate treatment <1% Severe disease carries a mortality of 26% Dengue is endemic in over 110 countries worldwide Dengue Map CDC: Distribution and Outbreaks (Past 6 months) Dengue Cases in the America 1990-2014 1
Dengue Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae: genus Flavivirus Most are transmitted by arthropods (mosquitoes or ticks) and are therefore referred to as arboviruses (arthropodborne viruses) Dengue- Serotypes There are four TYPES of virus which are called serotypes and these are referred to as DENV-1, DENV-2, DENV-3, DENV-4 Hence you can get dengue multiple times All four serotypes can cause the full spectrum of disease Infection with one serotype is believed to produce lifelong immunity to that serotype but only short term immunity against the others Dengue- Vector Dengue virus is primarily transmitted by Aedes mosquitoes particulaily A. aegypti yet also seen in A. albopictus These mosquitoes usually live between the latitudes of 35 N and 35 S below the elevation of 1000 meters (3300 ft.). They bite primarily during the day, around your ankles and knees Humans are the primary host but it also circulates in nonhuman primates Dengue Incubation period is 3-12 days from bite to the onset of symptoms This is very important especially when sorting out the cause of Fever in the Returning Traveller The virus is not contagious and cannot be spread from person to person It s an acute illness of sudden onset that usually follows a benign course with symptoms such as headache, fever, exhaustion, severe muscle and joint pains, Lymphadenopathy Rash Clinical Symptoms Clinical Signs 2
Laboratory Diagnosis Lymphopenia Thrombocytopenia Serology for Dengue IgM and IgG If there is a decrease in Hgb and albumin then this is a severe case i.e. DHF Treatment or Prevention There is no antiviral therapy for Dengue There is no tested and approved vaccine Treatment consists of symptomatic control and support with close monitoring of lab data and vitals Watch for the development of DHF Update: Lancet Feb 2018 However, after reassessment of data from the clinical trials, Sanofi warned on Nov 29, 2017, that the vaccine can increase the risk of severe dengue in patients who have never had Dengue. Studies have shown that giving the vaccine to people who have never been infected before can leave them vulnerable to a severe reaction if they are subsequently infected. WHO April 19, 2018- recommended it only be used in people who have previously been infected with the disease. Symptoms Dengue HF Lab Findings Thrombocytopenia Anemia Neutropenia Differential Diagnosis Case 2 Malaria Chikungunya Leptospirosis Typhoid fever Meningococcal disease Other viral infections, Parvovirus B19, Measles, EBV, CMV, HIV Drug fever A 56 year old female presents to you with an acute illness She was in Jamaica for two weeks on vacation. Upon returning home, seven days ago, she got fever, headache, rash on her legs and now has swollen and tender ankles and wrists 3
Case 2 What further info would you like to know? Lab Platelets 100 (150-300) WBC 4.9 with lymphopenia CRP 100 Mosquito vectors Predominantly Aedes aegypti and Aedes albopictus Same mosquitoes that transmit dengue Widely distributed throughout the World Aggressive daytime biters Aedes aegypti Aedes albopictus Chikungunya virus infection Majority (72%-92%) of infected people develop clinical symptoms Incubation period usually 3-7 days (range 1-12 days) Primary clinical symptoms are fever and polyarthralgia Fever and Polyarthralgia Fever Abrupt onset Typically >39.0 C Joint pain Often severe and debilitating Involves multiple joints Usually bilateral and symmetric Most common in hands and feet Other Clinical Signs & Symptoms Headache Myalgia Arthritis Conjunctivitis Nausea/vomiting Maculopapular rash Clinical Lab Findings Lymphopenia Thrombocytopenia Elevated creatinine Elevated liver enzymes- ALT, AST 4
Clinical Outcome Acute symptoms typically resolve in 7-10 days Mortality is rare Some patients have relapse or persistent rheumatologic symptoms for months or years Polyarthragia, Polyarthritis Tenosynovitis Raynaud's syndrome Diagnostic Testing Serology for IgM and confirmatory neutralizing antibodies Serology for >4-fold rise in virus-specific quantitative antibodies titers on paired sera Culture of virus or PCR for viral RNA Treatment of Chikungunya No specific antiviral therapy Supportive care with rest and fluids NSAIDS for acute fever and pain Persistent joint pain is the single major problem. Patients may benefit from use of NSAIDs, corticosteroids, hydroychloroquine or physiotherapy. What is Zika Virus Zika is a flavivirus, related to dengue, yellow fever, West Nile and JE Discovered in 1947 in the Zika forest of Uganda Transmitted by Aedes mosquitoes Incubation period 3-12 days 5
Zika Clinical Symptoms occur in 20-25% of infections Fever, rash, arthralgia, conjunctivitis, HA x~1 week GBS recognized in French Polynesia Virus detected in serum and saliva for ~7 d urine for ~10 d, semen for >60 days ZIKV Diagnosis Diagnosed by RT-PCR or serology IgM Serology is a pan-flavivirus done at BCCDC Serology is not 100% accurate No treatment or vaccine available Why is Zika a Problem Huge increase (>20 fold) in microcephaly coinciding with Zika outbreak in Brazil >1.5 M Zika infections since Feb 2015 >5000 cases microcephaly in Brazil Associations also reported in Latin America Zika and Fetus Anomalies Several affected fetuses/infants positive for Zika in brain, CSF Viral loads in amniotic fluid 4 logs higher than in blood of acutely infected adults Ocular involvement, hydrops, fetal death Pregnancy Outcomes after ZIKA Infection in French Territories in the Americas Hoen et al NEJM, March 15, 2018 Among pregnant women, PCR confirmed ZIKA infection, birth defects were present in 7% Defects were more likely if infection was early in pregnancy 1 st trimester 12.7% 2 nd trimester 3.6% 3 rd trimester 5.3% Zika Virus Shedding in Semen of Symptomatic Infected Men Mead et al, NEJM, April12, 2018 Conclusion ZIKA RNA was commonly present in the semen of men with symptomatic ZIKA infection and persisted for > 6 months Shedding of infectious ZIKA appeared to be much less ie <1 month 6
Persistence of Zika Virus in Body Fluids Final Report NEJM, Sept 27, 2018 In 95% of the men in this study, ZIKV RNA was cleared from semen after approximately 4 months. Answers to Common Questions Q: How long should you wait to try to become pregnant after traveling to an area with Zika? A: Women who have had symptoms of the virus or tested positive for it should wait at least eight weeks after their symptoms first appeared before trying to get pregnant, Men- Canada recommended that men who had symptoms should wait 6 months before having unprotected sex. Yet CDC in USA states 3 months (Updated August 2018) Common questions about Zika Q: Is the Zika test accurate? A: Asymptomatic patients: Routine testing is not currently recommended for nonpregnant women and men who have possible exposure to Zika virus but no clinical illness. No test is 100% accurate Questions about Zika Q: Do travellers who do not plan on conceiving need to be worried about Zika virus infection? A: Symptoms consist of fever, rash, arthralgia, conjunctivitis, HA x~1 week and a low risk of Guillain Barre Syndrome Can you get Infected in Canada with Zika Virus? Zika Virus infection is not acquired in Canada. The mosquitos that transmit Zika Virus and Dengue do not exist in Canada due to the climate. Canadian Results CMAJ March 6, 2017 Over 1 year- Oct 2015-Sept 2016 1118 visits to CanTravNet sites 41 patients (3.7%) with Zika Dx & 41 with Dengue. First half of the period primarily from VFRs to South America Second half from tourists to the Caribbean Islands 7
Canadian Data 40 patients from Mosquito bites One from sexual transmission Congenital transmission occurred in 2 of 3 pregnancies. Two (5%) of those with Zika had symptoms resembling those of Guillain Barré syndrome, 1 of whom also had Zika viral meningitis. Summary Dengue On the rise throughout the world especially in South and Central America and Caribbean Incubation period 2-12 days Associated with fever, rash, reduced WBC & platelets, No vaccine for travellers, Travellers need to use DEET and personal protection measures Summary Chikungunya Seen throughout the world yet decreased incidence especially in the Caribbean Fever, rash and significant almost debilitating polyarthralgia, associated with decreased WBC and Platelets No Vaccine Travellers need to use DEET and personal protection measures Summary Zika Virus Reduced incidence in South and Central America and Caribbean Associated with fever and rash yet 70% of patients who get infected have minimal to no symptoms. Birth defects can occur if infection during pregnancy ~3.4-12% incidence Women who visit endemic areas should not conceive for 8 weeks, Men should not conceive for 3-4 months (CDC) but 6 months may be safer ( Health Canada) 8