Zika, Dengue, Chikungunya...Zika, Dengue, Chikungunya after Irma, Maria and Harvey Pascal Bittel...

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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

Dengue

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

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

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

Incubation period 3–7 days

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

…but also other mosquito-borne viruses

West Nile Virus

Japanese Encephalitis Virus

La Crosse Virus

(Yellow Fever Virus)

St.Louis Encephalitis Virus

Diagnostic Techniques

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

● 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

Average rainfall

5.-13.2.2016

5.-21.8.2016

Risk to be stung by an Aedes mosquito

Worldwide tropical storm paths

12 NASA Earth Observatory

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

Climate

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

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

► 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

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

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

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?

Available data say NO, (but…)

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

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

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

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

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

Main Influencing Factors: Uncontrollable

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

Early in rainseason = risk of transmission may rise

Late in rainseason = risk may even decrease

Manmade Influencing Factors

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

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)

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

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

● Microbial control of human pathogens in adult vectors using Wolbachia and Incompatible insect technique (IIT) ● Sterile insect technique (SIT), Ae. aegypti OX513A

Ritchie SA, Johnson BJ.; J Infect Dis. 2017 Mar 1;215 Advances in Vector Control Science: Rear-and-Release Strategies Show Promise

● 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?

Ritchie SA, Johnson BJ.; J Infect Dis. 2017 Mar 1;215 Advances in Vector Control Science: Rear-and-Release Strategies Show Promise

Disease 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.

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?

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

Low-tech molecular diagnostics:

Summary

● 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?

time of year

location

disaster response

situation before event

Outbreak

Thank you for you attention

Questions?

Zika, Dengue, Chikungunya...Zika, Dengue, Chikungunya after Irma, Maria and Harvey Pascal Bittel...

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