Zika, Dengue, Chikungunya after Irma, Maria and Harvey

Pascal Bittel Institute for Infectious Diseases Universität Bern 08.03.2018, Molecular Diagnostics Symposium Zurich

Actors:

2

Pathogens Climate

Vectors Impact & Disease

Dengue

3

A potentially lethal disease affecting >50 mio pp/y Lead Syptoms High Fever Mild rash

Mild muscle pain

Moderate joint pain

Moderate headache

Moderate bleeding

Shock (DHF)

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)

Guzman, MG et al. The Lancet , Volume 385 , Issue 9966 , 453 - 465 Dengue

Zika

4

Lead Symptoms Low/Moderate Fever

Strong rash Conjunctivitis Moderate joint pain

Mild muscle pain

Mild headache

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

Chikungunya

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Lead Symptoms High Fever Mild Rash

Mild conjuctivitis

Strong joint pain & swelling Mild muscle pain

Moderate headache

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

Clinical Manifestation Summary

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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

…but also other mosquito-borne viruses

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West Nile Virus

Japanese Encephalitis Virus

La Crosse Virus

(Yellow Fever Virus)

St.Louis Encephalitis Virus

Diagnostic Techniques

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Serology Antigen Dengue rapidtests available (NS1Ag)

Molecular

IgM/G Crossreactions among flaviviruses

Only in acute phase (RT-PCR)

Cel. Virology Plaque Reduction Neutralization Test (Zika, Dengue; CDC)

https://www.swisstph.ch/en/travelclinic Information and recommendations of the Swiss Expert Committee of Travel Medicine (ECTM)

Main Vectors

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

Ae. albopictus

Ae. aegypti

Aedes Biology

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● 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 Pupa → Adult: 1-2 days ● Blood meal required to develop eggs

● Vertical virus transmission possible

aquatic, container breeder

Mosquitoborne-disease Season = Rainsaison

11 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

Den

gue

inci

denc

e

Average rainfall

98%

3.5%

5.-13.2.2016

5.-21.8.2016

Risk to be stung by an Aedes mosquito

Chr

isto

ph H

atz,

TPH

, 201

6

Worldwide tropical storm paths

12 NASA Earth Observatory

«Dengue-belt» Tracks and intensities of tropical storms 1951-2007

Climate

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HARVEY 215km/h 17.8.17-3.9.17

US National Hurricane Center; https://www.nhc.noaa.gov

IRMA 298km/h 30.8.17-14.9.17

MARIA 282km/h 16.9.17-30.9.17

Climate

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

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Impact and Aftermath

15 Zorilla CD, N Engl J Med 2017; 377:1801-1803 The View from Puerto Rico — Hurricane Maria and Its Aftermath

San Juan, Puerto Rico; Maria

“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”

St. Maarten; Irma

Arboviral diseases are not a 1. line priority

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► Flood water contaminated by fecal material: Typhoid fever and cholera

► Safety concerns including potential crime and violence

► Caring for those directly injured during the storm

► Inadequate food and water supplies

► Rebuilding of a basic functional infrastructure

The question

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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.

Facts pro

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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)

Facts contra

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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)

Post-Hurricane arboviral outbreaks?

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Available data say NO, (but…)

Post-Hurricane arboviral outbreaks?

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Available data say NO, (but…) Joe Posid, CDC

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● 11 cases within 3 weeks past-event ● only 1 out of 150 WNF-patients develops neuroinvasive disease

Post-Hurricane arboviral outbreaks?

The CDC's and ECDC’s opinion

23 https://www.cdc.gov/zika/vector/mosquitoes-and-hurricanes.html

“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?

Public awareness vs. empirical evidence

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Hurricane events increase incidence of cases

Hurricane events have little or no effect on incidence of cases, but…

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

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Affected areas have time to react (but also lots of other problems)

A complex network…

► Data must be integrated into multidisciplinary studies of pathogen dynamics and transmission risk

Mar

ian

Kam

ensk

y

Main Influencing Factors: Uncontrollable

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Early in rainseason = risk of transmission may rise

Late in rainseason = risk may even decrease

Time and location of the hurricane event is important:

Main Influencing Factors: Uncontrollable

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Early in rainseason = risk of transmission may rise

Late in rainseason = risk may even decrease

Manmade Influencing Factors

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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.

Governmental/Social efficiency for disaster control

Vector Surveillance / Mosquito control

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Recommendations of WHO Vector Control Advisory Group (VCAG)

http://www.who.int/neglected_diseases/news/mosquito_vector_control_response/en

● Vector traps ● Targeted residual spraying ● Space spraying ● Larval control (source reduction / larviciding) ● Personal protection measures (repellents)

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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

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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

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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

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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

Disease Surveillance

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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.

National surveillance and detection systems In non-industrialized countries often incomplete or non-existent. Little predictive value.

Multidisciplinary Surveillance

https://wwwn.cdc.gov/arbonet/

Virus surveillance?

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Isothermal amplification methods? A tool for field virus surveillance..?

Low-tech molecular diagnostics:

Summary

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● Hurricane events can create new mosquito breeding sites.

● Recovery of mosquito population typically takes some weeks.

● Adult mosquitos generally do not survive hurricane level storms.

● The dangers of post-hurricane arboviral outbreaks are often exaggerated in mass media.

● No major post-hurricane arboviral outbreaks have been reported However, if conditions are right, post-hurricane arboviral outbreaks can’t be excluded

Arboviral outbreak after hurricane-event?

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time of year

location

disaster response

situation before event

Outbreak

Thank you for you attention

Questions?

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