CDC Entomology Activities: Malaria & Zika

8 September 2016

Bob Wirtz, PhD

Retired CDC Entomology Branch Chief &

Emergency Operations Center Zika Virus Vector Team Lead

The views expressed are my own and do not

represent the CDC or the US Government

Department of Health and Human Services (HHS)

US Public Health Service (USPHS)

Centers for Disease Control and Prevention (CDC)

~9,400 FTEs + ~5,000 contractors

~6,500 FTEs in Atlanta at 4 campuses

National Center for Emerging & Zoonotic Infectious Diseases

Division of Vector-Bone Diseases (Ft. Collins)

Arboviral Diseases, Bacterial Diseases,

Rickettsial Zoonoses and Dengue Branches

Center for Global Health

Division of Parasitic Diseases and Malaria (Atlanta)

Malaria, Parasitic Diseases & Entomology Branches

CDC Entomology Activities

World’s Most Dangerous Animals

Human Malaria

Plasmodium protozoa infection

transmitted by Anopheles

mosquitoes

P. falciparum

P. vivax

P. malariae

P. ovale

P. knowlesi

Eliminated in US by 1951

Collection and Identification of Malaria Vectors

• ~30 of ~430 Anopheles species

are major vectors of human

malarias

• Collection, identification and

incrimination are challenges

• Changes with ecology and

climate, and in response to

interventions

Human landing collections

President’s Malaria Initiative (PMI)

• 30 June 2005 start of a 5-year, $1.2 billion initiative to rapidly scale

up malaria control interventions in 15 high burden countries in

Africa

• Goal: Reduce malaria-related mortality by 50% in selected

countries in sub-Sarah Africa

• Increase funding from other international donors

PMI Interventions

• Insecticide-treated bed nets

(ITNs)

• Indoor residual spraying (IRS)

• Artemisinin-based combination

therapy

• Intermittent preventive

treatment in pregnancy

CDC/KEMRI Field Station Bed Net Study

Asembo

Gem

Provincial

Hospital

Kisumu

Lake Victoria

CDC/KEMRI

laboratory

at Kisian Equator

KENYA

Bed Net Distribution

ITNs

Mosquitoes

Healthier

pregnancies

Healthier

children

Improved infant and

child survival

95% Fewer An. gambiae

90% Reduction in transmission

38% Parasitemia

47% Severe anemia

35% Placental malaria

28% Low birth weight

74% Malaria attack rate

60% Incidence of severe anemia

27% Sick child visits to the clinic 26% Infant mortality

14% Child (1-4yr) mortality

Kisumu ITN Summary: ~120,000 people

ITN Summary • ITNs as cost-effective as childhood vaccines

• Distribution integrated with immunization, Vitamin A, de-worming,

HIV/TB, & nutrition campaigns

• Subsequent development of long-lasting ITNs (LLINs)

• Now over one billion LLINs distributed

Highly effective & entire household protected

No change in human behavior required

• Lasts 4-10 months

• Only method for managing insecticide resistance

• Cost & sustainability

• 2015 PMI Results: – 13 countries

– 4.3M houses sprayed

– 16.7M people protected

– 37,000 people trained Photo courtesy

of Dr Mark Benedict

Indoor Residual Spraying

Malaria Deaths in Children Aged <5 years by WHO Region, 2015

PMI 2005–2015: A Decade of USG Commitment

2016

$870M

Malaria 2015: Worldwide

>200 million new infections annually; >500,000/day

>300,000 deaths/yr; a child dies about every 2 minutes

~3.2B at risk (~50% population)

Endemic in 95 countries

Primarily a disease of the poor

~10,000 travelers from Europe and ~1,500 each in

Japan and North America contract malaria each year

Malaria Control Challenges

No highly effective vaccine

Bed net physical durability

Political instability

Insecticide resistance

Changes in vector behavior

Drugs:

• Resistance

• Expensive/counterfeited

Insufficient funding

Successful IR Management

Bayoh (2010) Malaria Journal 2010, 9:62

Change Vector Populations & Behaviour with LLIN/IRS

An. arabiensis (bottom, green bars)

An. gambiae s.s. (top, black bars)

Source: WHO, 2016

Anti-malaria Drugs

• Artemisinin Resistance in Mekong

Sub-region (Feb 2016)

• Tier 1: reported resistance

• Tier 2: suspected resistance

• Tier 3: no known resistance

• Drug quality:

• Substandard and counterfeits • >50% OTC tablets SE counterfeit

Global Investment for Malaria Control, 2005–2014

In 2014, global financing 2.5 billion USD – only half of projected needs

Zika Arbovirus

• One of ~500 viruses suspected of

being transmitted by arthropods

• ssRNA member Flaviviridae family

• Spread by Aedes species

mosquitoes

• Related to the dengue, yellow fever,

Japanese encephalitis & West Nile

• ~80% Zika infections with no or

mild symptoms

1948: Uganda-Isolation from Ae. africanus

1969-2001: Ae. aegypti & other Aedes implicated

Zika Virus Transmission

• World-wide: 65 countries, 48

of them for the first time

• Primarily by mosquitoes, also

sexual & blood transfusion

• Virus detected in blood, urine,

semen, breast milk & saliva

• Range expanding with new

susceptible populations

• The Americas:

• Dec 2015: 10 countries

• Apr 2016: 28 countries

• July 2016: 40 countries/

territories reporting

locally acquired cases

Dengue, chikungunya and Zika virus cases in the Americas

2013-2016*

*Data as of EW 23, 2016

Source: Surveillance reports to PAHO/WHO from countries/territories in the Americas

Zika Causes Microcephaly and Other Birth Defects

First mosquito-borne cause of birth defects

Microcephaly and range of devastating congenital brain and limb damage

Microcephaly infants will have life-long, severe disability: cost/child est. >$10M

Unknown: Range of Congenital Zika Syndrome and other effects in infants with normal head size

Unknown: Impact on children and adults, e.g., Guillain–Barré syndrome in 7 Latin American countries with >1,500 cases total

World-wide: ~1.6 million new infections & ~5,235 Zika-related microcephaly cases

Martines, R.B., et al. The Lancet. S0140-6736(16)30883-2. 2016. Rasmussen, S.A. et al. New England Journal of Medicine. 374(20):1981-7. 2016.

Zika Prevention and Control

Vaccine: none, 1-2 years until available

Preventative or therapeutic drugs: None

Personal protection: Repellents, Prevention Kits for pregnant women

Ae. aegypti control through Integrated Vector Management (IVM)

– Comprehensive, sustainable and environmentally responsible

– Structural barriers, such as screens and air conditioning, if possible

– Reducing standing water and eliminating larval habitat

– Killing adult and larval mosquitoes

– Active disease and mosquito surveillance for targeting interventions

Dengue, chikungunya and Zika virus cases in the Americas 2013-2016*

*Data as of EW 23, 2016

Source: Surveillance reports to PAHO/WHO from countries/territories in the Americas

Can IVM Interrupt Arbovirus Transmission?

Cuban Yellow Fever Commission 1902:

• Transmission by Ae. Aegypti

• Demonstrated Control:

– Isolating patients

– Controlling Ae. Aegypti

– 1,400 > 37 > 0 cases

Panama Canal Commission 1904-14:

• Military style approach

• Fumigators visited ever home repeatedly

• Screened hospitals & homes

• Drained/oiled standing water

• Patients isolated & tracked

• Priority for requisitions & resources

• Largely eliminated yellow fever

• Significantly reduced malaria

Puerto Rico 2016: ZIKA the Silent Epidemic

Dengue, chikungunya & Zika

spread by same mosquitos

Dengue has infected 80-90% of

people in Puerto Rico

Chikungunya infected 1 of every

4 people in less than a year

Zika: Silent epidemic – no/minor

symptoms in 80% those infected

Zika, dengue and chikungunya cases reported

Puerto Rico - 2015 to 2016

Source: Dirlikov E, Ryff KR, Torres-Aponte J, et al. Update: Ongoing Zika Virus Transmission — Puerto Rico, November 1, 2015–April 14,

2016. MMWR Morb Mortal Wkly Rep 2016;65:451–455. DOI: http://dx.doi.org/10.15585/mmwr.mm6517e2

Stopping Zika Transmission

Experience with dengue

suggest >80% reduction

in Ae. aegypti mosquito

population likely needed

to reduce spread of virus

Only aerial applications of

Naled can potentially kill

80%+ of mosquitoes –

and can do so in weeks

-100%

-80%

-60%

-40%

-20%

0%

Reducing standingwater

Community-basedlarviciding

Aerial applicationof Bti larvicide

Aerial application ofproducts that killadult mosquitoes

Per

cen

t d

eclin

e in

mo

squ

ito

es

Minimum level to reduce disease spread

Effective within weeks

Takes months to be effective

Aerial Ultra-low Volume Spraying with Naled (1 ounce/acre)

Florida – reduced mosquito populations by 99.2%

Louisiana – reduced mosquito populations 79.2 - 99.7%

CDC Recommends Aerial Application of Naled for Ae. aegypti

Early July 2016: Zika is spreading quickly;

Estimated >1,500 pregnant women

infected, with up to 50 more every day

Ae. aegypti resistant to pyrethroids

ULV Naled is routinely used in the US –

average of ~16M acres/year in >12 States

No other method works nearly as quickly

Pre-aerial ULV program plan implemented

with spraying scheduled for July 22

Puerto Rico Zika Situation

July 21: PR Governor failed to approval aerial spraying with Naled due to

widespread public disapproval, and all program planning halted

Currently:

– >8,700 confirmed Zika cases

– ~1% of blood donations Zika positive

– No effective mosquito control agency

– Limited funding for mosquito control

– Lawsuit filed to stop use of Naled

– Exploring use of screening and new traps

– Awaiting births from Zika-infected mothers In2Care Trap

Emergency Operations Center Activated Jan 22

Elevated Level 1 – Feb 8

• Over 2,686 confirmed travel-related

cases (23 sexual & 7 GBS)

• KS has 13 cases reported

• Tracking ~624 pregnant women with

confirmed infection

• Tracking 16 infants with birth defects

• 5 pregnancy losses with birth defects

• FDA: All blood donations to be screened

• Developing and/or evaluating new:

• Prevention modalities & diagnostics

• Strengthening State IVM capacity

• Drug and vaccine development

• Progress dependent on increased

Congressional funding

US Zika Situation – 31 Aug 2016

• July 28: Blood donations in Miami &

• Broward halted and IVM implemented

• July 29: Local transmission announced

• Aug 1: CDC travel warning

• Aug 4: Aerial spraying of Naled

• Sep 1: Infected Ae. Aegypti pools

• Sep 1: Hurricane hits northern FL

• Sep 7: 56 local transmission cases

596 travel related cases

80 in pregnant women

• Increased surveillance & IVM state-wide

Florida Zika Summary (FL Department of Health Report of 7 Sep 2016)

Wynwood & Miami Beach, FL

Wolbachia

• Naturally occurring bacteria

• Lives inside insect cells

• Transmitted from parent to

offspring through the eggs

• Not be transmitted to warm-

blooded animals

• Safe for humans, other animals

and the environment

• Dramatically reduces arbovirus

transmission by mosquitoes

INSECT SPECIES

HAVE WOLBACHIA

Aedes aegypti

Dengue: before & after Wolbachia release

Pre-release (Jan 1995 – Dec 2012) 34% (647)

Post-release (May 2013 – Dec 2015) 4% (74)

Confirmed and probable dengue cases identified through Queensland’s Notifiable Disease Surveillance System; p<0.0001

Release area

Applications of Spectroscopy to Medical Entomology

• Species identification

• Sexing tsetse pupae

• Age grading

• Drug analysis/counterfeit ID

• Insecticide levels on LLINs

• Wolbachia-infected mosquitoes

NIRS Configuration for Species Identification

And Age determination of Mosquitoes

The Mosquito Net – by John Singer Sargent