Zika, Dengue, Chikungunya after Irma, Maria and Harvey

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Zika, Dengue, Chikungunya after Irma, Maria and Harvey Pascal Bittel Institute for Infectious Diseases Universität Bern 08.03.2018, Molecular Diagnostics Symposium Zurich

Actors: Pathogens Climate Vectors Impact & Disease 2

Dengue A potentially lethal disease affecting >50 mio pp/y DENV; ssrna Flavivirus (Flaviviridae), 4 genotypes Transmission via mosquitos Exposure gives immunity to the same strain, but not others. Secondary infection with different strain can lead to DHF (2.5% of DHF are lethal) Incubation period 3-7 days Vaccine available (Dengvaxia) Lead Syptoms High Fever Mild rash Mild muscle pain Moderate joint pain Moderate headache Moderate bleeding Shock (DHF) Guzman, MG et al. The Lancet, Volume 385, Issue 9966, 453-465 Dengue 3

Zika The emerging arboviral pathogen of 2016 ZIKV; ssrna Flavivirus (Flaviviridae) WHO 2016 International Public Health Emergency Transmission via mosquitos, sexual and intrauterine Linked to birth defects (Microcephaly) Linked to Guillain-Barré-Syndrome Incubation period 3 12 days Lead Symptoms Low/Moderate Fever Strong rash Conjunctivitis Moderate joint pain Mild muscle pain Mild headache 4

Chikungunya The painful third CHIKV; ssrna Alphavirus (Togaviridae) Transmission via mosquitos Some patients with persistent joint pains for months to years Incubation period 3 7 days Lead Symptoms High Fever Mild Rash Mild conjuctivitis Strong joint pain & swelling Mild muscle pain Moderate headache 5

Clinical Manifestation Summary Symptom Dengue Chikungunya Zika (80% asymptomatic) Fever ++++ ++++ ++ Headache +++ ++ + Rash ++ ++ +++ Conjunctivitis + ++ ++ retro orbital pain ++ + + muscle pain ++ + ++ joint pain/swelling + +++ ++ gastrointestinal symptoms + ++ + Pruritus/dysaesthesia ++ + ++ Petechiae + - - spontaneous bleeding + (+) - Modified from Blum & Hatz, 2009; Neumayr & Hatz, 2016 6

but also other mosquito-borne viruses West Nile Virus St.Louis Encephalitis Virus Japanese Encephalitis Virus (Yellow Fever Virus) La Crosse Virus 7

Diagnostic Techniques Serology Cel. Virology Molecular Antigen Dengue rapidtests available (NS1Ag) IgM/G Crossreactions among flaviviruses Plaque Reduction Neutralization Test (Zika, Dengue; CDC) Only in acute phase (RT-PCR) https://www.swisstph.ch/en/travelclinic Information and recommendations of the Swiss Expert Committee of Travel Medicine (ECTM) 8

Main Vectors Ae. aegypti Ae. albopictus Kraemer, M. et al. Elife. 2015 Jun 30;4:e08347 The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus 9

Aedes Biology Adult life span: 14-21 days Female lays eggs 3-4 times in her life ca. 100-200 eggs per oviposition Egg Larva: 2-3 days Larva Pupa: 4-5 days aquatic, container breeder Pupa Adult: 1-2 days Blood meal required to develop eggs Vertical virus transmission possible 10

Mosquitoborne-disease Season = Rainsaison 98% Dengue incidence 5.-13.2.2016 Risk to be stung by an Aedes mosquito 3.5% Average rainfall 5.-21.8.2016 Christoph Hatz, TPH, 2016 Wiwanitkit V. J Vector Borne Dis. 2006 Jun;43(2):73-6. An observation on correlation between rainfall and the prevalence of clinical cases of dengue in Thailand 11

Worldwide tropical storm paths Tracks and intensities of tropical storms 1951-2007 «Dengue-belt» NASA Earth Observatory 12

Climate HARVEY 215km/h 17.8.17-3.9.17 IRMA 298km/h 30.8.17-14.9.17 MARIA 282km/h 16.9.17-30.9.17 US National Hurricane Center; https://www.nhc.noaa.gov 13

Climate Atlantic Hurricane Season: Pacific Hurricane Season: Pacific Typhoon Season: Australian / Southern Cyclone Season: June November Sept May September Sept June October Aug November April Feb 14

Impact and Aftermath San Juan, Puerto Rico; Maria St. Maarten; Irma As of 16 days after the hurricane, 25 of 69 hospitals were working, only 9.2% of people had power, 54% had water, 45% had cell phone service Zorilla CD, N Engl J Med 2017; 377:1801-1803 The View from Puerto Rico Hurricane Maria and Its Aftermath 15

16 Arboviral diseases are not a 1. line priority Caring for those directly injured during the storm Inadequate food and water supplies Flood water contaminated by fecal material: Typhoid fever and cholera Rebuilding of a basic functional infrastructure Safety concerns including potential crime and violence

The question Hurricane events increase the incidence of cases of mosquito-arboviral diseases. or Hurricane events have little or no effect on the incidence of cases of mosquito-arboviral diseases. 17

Facts pro Hurricane events increase incidence of cases Increased rainfall and flooding Accumulation of water puddles: New breeding grounds for mosquitoes Mosquito populations may increase Suspended vector control measures Displacement of large numbers of people into crowded shelters / camps (3. world, global south) 18

Facts contra Hurricane events have little or no effect on the incidence of cases Strong winds, salt water surge, downpours: Displace or kill mosquitoes, «flush-out effects» Adult Mosquitos don t survive hurricane level storms Altered ecology past event: Disruption of vertical transmission: New freshly hatched mosquitoes are virus-free Weeks for recovery of virus in population Mass-evacuation of people to less affected (e.g. dry) inland-areas: Reduction of active reservoires (1. world) 19

Post-Hurricane arboviral outbreaks? Available data say NO, (but ) 20

Post-Hurricane arboviral outbreaks? Joe Posid, CDC Available data say NO, (but ) 21

Post-Hurricane arboviral outbreaks? 11 cases within 3 weeks past-event only 1 out of 150 WNF-patients develops neuroinvasive disease 22

The CDC's and ECDC s opinion Although flooding caused by hurricanes can be severe and an increase in mosquito populations is expected in the coming weeks, CDC does not generally expect to see a substantial increase in the incidence of mosquito-borne diseases. But why is the topic so much discussed then? https://www.cdc.gov/zika/vector/mosquitoes-and-hurricanes.html 23

Public awareness vs. empirical evidence Hurricane events increase incidence of cases Hurricane events have little or no effect on incidence of cases, but 24

If, then late Mosquito-borne diseases are hurricane late-consequences: Mosquito population has to rebuild: weeks (most adults are dead) Virus has to reestablish in the mosquito population Affected areas have time to react (but also lots of other problems) 25

A complex network Data must be integrated into multidisciplinary studies of pathogen dynamics and transmission risk Marian Kamensky

Main Influencing Factors: Uncontrollable Time and location of the hurricane event is important: Early in rainseason = risk of transmission may rise Late in rainseason = risk may even decrease 27

Main Influencing Factors: Uncontrollable Early in rainseason = risk of transmission may rise Late in rainseason = risk may even decrease 28

Manmade Influencing Factors Governmental/Social efficiency for disaster control Basic needs have to be fullfilled before affected areas can «switch back from disaster survival mentality» Mosquito control is not a 1st priority action after a major hurricane event. 29

Vector Surveillance / Mosquito control Recommendations of WHO Vector Control Advisory Group (VCAG) Vector traps Targeted residual spraying Space spraying Larval control (source reduction / larviciding) Personal protection measures (repellents) http://www.who.int/neglected_diseases/news/mosquito_vector_control_response/en 30

Advanced Mosquito control techniques Microbial control of human pathogens in adult vectors using Wolbachia and Incompatible insect technique (IIT) Terradas G, McGraw EA.; Curr Opin Insect Sci. 2017 Aug;22:37-44. Wolbachia-mediated virus blocking in the mosquito vector Aedes aegypti 31

Advanced Mosquito control techniques Ritchie SA et al.; Trends Parasitol. 2018 Mar;34(3):217-226 Mission Accomplished? We Need a Guide to the 'Post Release' World of Wolbachia for Aedes-borne Disease Control 32

Advanced Mosquito control techniques Microbial control of human pathogens in adult vectors using Wolbachia and Incompatible insect technique (IIT) Sterile insect technique (SIT), Ae. aegypti OX513A Terradas G, McGraw EA.; Curr Opin Insect Sci. 2017 Aug;22:37-44. Wolbachia-mediated virus blocking in the mosquito vector Aedes aegypti Ritchie SA, Johnson BJ.; J Infect Dis. 2017 Mar 1;215 Advances in Vector Control Science: Rear-and-Release Strategies Show Promise 33

Advanced Mosquito control techniques Microbial control of human pathogens in adult vectors using Wolbachia and Incompatible insect technique (IIT) Sterile insect technique (SIT), Ae. aegypti OX513A Hurricane events as chances? Terradas G, McGraw EA.; Curr Opin Insect Sci. 2017 Aug;22:37-44. Wolbachia-mediated virus blocking in the mosquito vector Aedes aegypti Ritchie SA, Johnson BJ.; J Infect Dis. 2017 Mar 1;215 Advances in Vector Control Science: Rear-and-Release Strategies Show Promise 34

Disease Surveillance National surveillance and detection systems In non-industrialized countries often incomplete or non-existent. Little predictive value. Multidisciplinary Surveillance CDC Arbonet: US national arboviral surveillance system Operational since 2000. Passive surveillance system. Clinicians/scientists obtaining the appropriate diagnostic tests, reporting the diagnosis of arboviral diseases, laboratory-analysis and vector surveillance data. Can be combined with climate data. Actively curated and can be used as a modelling instrument. 35 https://wwwn.cdc.gov/arbonet/

Virus surveillance? Low-tech molecular diagnostics: Isothermal amplification methods? A tool for field virus surveillance..? 36

Summary Adult mosquitos generally do not survive hurricane level storms. Hurricane events can create new mosquito breeding sites. Recovery of mosquito population typically takes some weeks. No major post-hurricane arboviral outbreaks have been reported However, if conditions are right, post-hurricane arboviral outbreaks can t be excluded The dangers of post-hurricane arboviral outbreaks are often exaggerated in mass media. 37

Arboviral outbreak after hurricane-event? situation before event location time of year Outbreak disaster response 38

Thank you for you attention Questions? 39