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FOUNDATION
Emerging and
Re-Emerging Infectious
Diseases:
From AIDS to Zika
Anthony S. Fauci, M.D.
Director
National Institute of Allergy and
Infectious Diseases
National Institutes of Health pr
July 18, 2017 NIH) aro Dscases ‘White House Holds
Disaster-Response
| Exercise with
Trump Officials TheNlHRecord
U.S. Department
of Heath 084)
Human Services
November 20 National
Inatiutes
Vol. xvi ot
Dr. Anthony Fauci, Expert on
No. 24 Heath
Immunity and AIDS, Named
Director of Nat'l. Institute of Allergy and Infectious Diseases
Dr. Anthony 8. Fauci has been named Di
rector of the National institute of Allergy and
Infectious Diseases, effective Nov. 2.
INIAID conducts and supports research to
better understand the causes of allergic,
immunologe and Infectious diseases, and to
develop better means of preventing. diag
fosing and treating such ilnesses,
‘Dr Favel, 43, an internationally renowned
‘expert on the immune system, has been chief
OI NIAID's Laboratory of immunoregulation|
Since 1980 and deputy clinical director ofthe
Institute since 1977,
T/am extremely pleased that Dr. Fauci will
take over the leadership ofthis important in
siilue,” HHS Secretary Margaret M. Heckler
faid i announeing the appointment. "His
tique background, particulary inthe fields
‘of immunology and infectious diseases, wil
be of key importance in maintaining and
accelerating our momentum in these crucial
r. Faucl I internationally renowned fr his
expertise on the immune system.
a Five Administrations and Emerging
Infectious Diseases
Ronald W. Reagan 1981 - 1989 George H.W. Bush 1989 - 1993
a
7 ia
William J. Clinton 1993 - 2001 George W. Bush 2001 - 2009
i
Barack H. Obama 2009 - 2017 Testimony before
the House
Appropriations
Subcommittee
for NIH - 1980s Global Examples of Emerging and
Re-Emerging Infectious Diseases
© Newly emerging
© Re-emerging/resurging @ “Deliberately emerging” Global Examples of Emerging and
Re-Emerging Infectious Diseases
© Newly emerging
© Re-emerging/resurging @ “Deliberately emerging” Global Examples of Emerging and
Re-Emerging Infectious Diseases
Antimicrobial West Nile virus Cryptosporidiosis Ebola virus disease Diphtheria
resistant threats. coli i 7
“CRI Drug-resistant malaria
= MRSA
=. difficile
= N. gonorrhoeae
Rift Valley fever
‘Typhoid fever
HaN2Vinfuonza, Stnyavius
Cyetoeporiass, col
E coV O1S7-H7 oiSrkr
Human
monkeypox
Titertsie dC" se
Bourbon Pp 2 io influenza
virus ER : Het
Ss influenza
2009 HiNt 3 SS
influenza by g \ SS SARS
Adenovirus 14 ai Nipah
fare L wea
bioterrorism: i Hendra
virus
Hantavirus’
pulmonary Dengue Ls Human monkeypox
Byndrome —Zika virus = << Ebola virus disease
encw level 1 Marburg MDR/XDR tuberculosis Zika virus
Human African trypanosomiasis Choiera hemorrhagic fever peo
© Newly emerging © Re-emerging/resurging @“Deliberately emerging” | _,,...., HIV/AIDS
Ronald W. Reagan
1981 — 1989 CENTERS FOR DISEASE CONTROL
MNWR
MORBIDITY AND MORTALITY WEEKLY REPORT
June 5, 1981
Pneumocystis Pneumonia -
Los Angeles
July 3, 1981
Kaposi’s Sarcoma and
Pneumocystis Pneumonia
Among Homosexual Men —
New York City and California 1 dune 1982 Volume 96 Number 6
Annals of Internal Medicine
Published Twice Monthly by the American College of Physicians.
The Syndrome of Kaposi’s
Sarcoma and
Opportunistic Infections:
An Epidemiologically
Restricted Disorder of
Immunoregulation
Anthony S. Fauci, M.D.
"because we do not
know the cause of this
syndrome, any
assumption that the
syndrome will remain
restricted to a particular
segment of our society
is truly an assumption
without scientific
basis." The Global HIV/AIDS Pandemic:
Current Estimates
= 36.7 million people living with HIV
(end-2015)
= 1.1 million AIDS deaths in 2015
@ 2.1 million new HIV infections in 2015
@) UNAIDS
Source: UNAIDS, 11/2016 HIV/AIDS
George H. W. Bush
1989 — 1993 NIH HIV/AIDS Research Funding,
FY 1982 to FY 1993
1.25
Dollars in
0.25
0
ee ee ee ee ee
Fiscal Year Advances in HIV/AIDS Science,
1981-2017
Epidemiology Natural History
Etiology Virology Diagnosis
Pathogenesis Prevention
Treatment Vaccine Development Advances in HIV/AIDS Science,
1981-2017
Epidemiology | Natural History |
Etiology Virology | Diagnosis |
| Pathogenesis | Prevention
__Treatment | Vaccine Development | Rounds at NIH Clinical Center,
Early 1980s - AIDS Patient
Median survival of AIDS patients: ~8-15 months FDA-Approved Antiretroviral Drugs
NRTI
@5 multi-drug Mi Stavudine
combinations m Tenofovir
@ Abacavir (TDF, TAF)
M Didanosine M® Zidovudine
@ Emtricitabine
Lamivudine
= 2 ~ >»
Pharmacokinetic
NNRTI
MDelavirdine MM Nevirapine
@ Efavirenz @Rilpivirine
@ Etravirine
Integrase Inhibitors
™@ Dolutegravir Mi Raltegravir
@ Elvitegravir
Source: AlDSinto.nih.gov, 1/2017.
aes ™3/Enhancers
Mi Cobicistat
Bi Ritonavir
Pl Multi-Class
M Atazanavir Combinations
@ Darunavir BAtripla
@Fosamprenavir || ™ Complera
@ indinavir a Genveya
Hl Lopinavir/ pee
Ritonavir 7 ee
@ Nelfinavir
@ Ritonavir Fusion Inhibitor
i Saquinavir @Enfuvirtide
i Tipranavir Entry Inhibitor
@ Maraviroc Life Expectancy for 20-Year-Old Newly
Diagnosed with HIV, 1980s and Today
1980s 1-2 years from
(no ART) § AIDS diagnosis
Today ~53
(on ART) years
Source: JL Marcus et al., JAIDS, 2016. Tailored Prevention Using HIV
Prevention Toolkit
Provision of vesting!
Bornan ARVs for PMTCT, : spears as
Services PEP, PrEP revention
Blood Supply Medical Male
Screening Circumcision
=» Condoms
STI Treatment
Education/Behavior Microbicides
Modification
Clean Treatment/Prevention
Syringes —_ of Drug/Alcohol Abuse sly 25,2001
The AIDS Research Model
Implications for Other Infectious
Diseases of Global Health Importance
GK Folkers and AS Fauci William J. Clinton
1993 — 2001
HIV/AIDS
West Nile Virus
H5N1 Influenza
Antimicrobial
Resistance Meeting at the White House to Discuss
AIDS Research, Dec. 3, 1996 Commencement Address by President
Clinton at Morgan State University,
Baltimore, May 18, 1997
"If America commits to __—
find an AIDS vaccine S
and we enlist others in
our cause, we will do
it... VRC Research: From HIV to Zika
@ HIV
@ West Nile virus
@ Chikungunya
@ Ebola/Marburg
@ Influenza
@ Malaria
@ MERS-Cov
@ RSV
@ Tuberculosis
@ Venezuelan, Eastern,
and Western equine
encephalitis viruses
i Zika Global Examples of Emerging and
Re-Emerging Infectious Diseases
is_Ebola virus disease Diphtheri
E.coli Y
Oto4eHa / Drug-resistant malaria /”
_ MERS-CoV
Akhmeta virus
_ Rift Valley fever
Typhoid fever
SFTSv
'N. gonorrhoeae
Cyclospori ~ oe
a sve
monkeypox — influenza
" 1 i
faeces influenza
aa ne
Chikungunye/ y ee
pulmonary Dengue ~L / Human monkeypox
Eyndrome—Zikavirus 74 << epola virus disease
© Newly emerging © Re-emerging/resurging + @ “Deliberately emerging” Global Distribution of West Nile Virus, 1999
> U.S. West Nile Virus Cases,
1999-2016
10,000,
7
9862
264
Cases
Deaths
4269
oy 177 3630
3000 [i "24
2539 119
100
1356
44° 720 ye 712
66 32 43
2469
119 2205 2175 2038,
97 146 94
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016"
Source: CDC
Year
*As of Jan. 17, 2017 A
George W. Bush
2001-2009
HIV/AIDS
Anthrax
H5N1 Influenza
SARS Juxtaposition of Events of September 11,
2001 and the Deliberate Release of Anthrax
30 Rocrtrecien
New tos, NYdoate Bintorroniann A Clear and
Present Danger
HC Lane, J La Montagne and AS Fauci NIAID Strategic Plan for
teu aca
Responding
Through
Research February 5, 2002
President GW Bush: “Tony, what scares you the most among
potential microbial threats that a terrorist might use?”
Fauci: “Mr. President, | worry more about the natural occurrence
of an influenza pandemic and the ongoing plague of HIV than |
do about a bioterror attack.” Newsday
The Worst
Bioterrorist May Be
Nature Itself The
“ay New England
Journal of Medicine
VOLUME 353 SI NUMBER 13
REVIEW ARTICLE
Avian Influenza A (H5N1)
Infection in Humans
The Writing Committee of the World Health Organization
(WHO) Consultation on Human Influenza A/H5 Pandemic Influenza Preparedness
Strategy and Implementation
International Surveillance
Domestic Surveillance
Vaccines
Antivirals
Communications
State and Local
Preparedness Global Examples of Emerging and
Re-Emerging Infectious Diseases
Antimicrobial- West Nile virus ___Cryptosporidiosis Ebola virus disease Diphtheria MERS-Cov
resistant threats \ Powassan—//\ col fo
Enterovirus) Akhmeta virus
CRE N vir Drug-resistant malaria //
aga N88. rus /_\.0104:a / Drug’ eZ Rift Valley fever
“C. difficile
Typhoid fever
'N. gonorrhoeae bi
H3N2V influenza
Cyclosporiasis
coll
E coll OvS7:H7 —Z “cal
sases pie
men influenza
rmonkeyior J Bie
Teteriosis | influenza
Ponce } sn
soni 4 influenza
influenza
‘Adenovirus 14”\ Nipah
Anthrax
bioterrorism ~ Hendra
Chicurguny Enterovirus 71
pulmonary Dengue ~L / < Human monkeypox
Synarome—Zika virus ee “Ebola virus disease
j Nf
Yellowfever /||/Z7 Marburg MDR/XOR tuberculo
\ Zika virus
Human African trypanosomia:
Choiera hemorrhagic fever Plague
© Newly emerging © Re-emerging/resurging _@ “Deliberately emerging” SARS: A New Challenge to Global Health Early Cases of SARS: Guangdong
Province, China
Guangdong
Taiwan
—
e
Foshan
ee Feb 11-12, 2003: China
jong Kong
reports 305 cases of acute
respiratory syndrome in
Guangdong Province
South China Sea 2003 Spread of SARS from Hotel
Metropole in Hong Kong
= 5
Local Hospitals
‘and Community
eS
Nee J y
vu ¢
Sources: MMWR, March 28, 2003; WHO, 2003 Cumulative Reported Cases of SARS
November 1, 2002 to July 31, 2003
ues
rc}
a ey
3(0) S.Korea
251 (43)
346 (37),
‘ Hong Kong
United States 1,755 (299)
27 (0)
[OS> Philippines
+ 48@)
Singspore
238 03)
South Africa Australia
4) 50)
8,096 cases (774 deaths)
Indonesia
2(0)
‘New Zealand
10)
‘Source: WHO @ H1iN1
Pandemic
Influenza
lm MERS
HM Chikungunya
@ Ebola
@ Zika
H Antimicrobial
Resistance
7h
Barack H. Obama
2009-2017 Global Examples of Emerging and
Re-Emerging Infectious Diseases
‘Antimicroblal- West Nile virus __Cryptosporidiosis Ebola virus disease Diphtheria MERS-CoV
resistant threats Ey \ Powassan E. coll 7 Akhmet
CRE \Enterovirus\, Poviits o104H4 / Drug-resistant malaria, meta virus
MRSA \ 068, \ ES Z Rift Valley fever
fst National Institutes of Health
Turning Discovery into Health
™ NiH News Thursday, April 9, 2015
National Institutes of Health
Patient Admitted With
Ebola Virus Disease
Discharged From NIH
Clinical Center Global Examples of Emerging and
Re-Emerging Infectious Diseases
Antimicrobial- West Nile virus ___Cryptosporidiosis Ebola virus disease Diphtheri
resistant threats Powassan \ 4
. /\._€.coli Y
CRE \Enterovirus\, Pevirs \ of08%Ha /Drug-resistant malaria //
MRSA \ “
= ¢. difficile
N. gonorrhoeae
_ MERS-CoV
Akhmeta virus
_ Rift Valley fever
Typhoid fever
HaN2V influena bunyavirus
Cyclosporiasie are
E. coli 0157:H7 —4 = = : — O157:H7
Measles —2—
f10N9
rene einen
7] on
ora VAX tasea X | HSN
2000 HIN Y Neve ~) PNnan
influenza “\ SARS
Adenovirus 18 won
‘anthrax
bioteranicns a
Chikungunya 7
Enterovirus 71
Human monkeypox
af
Hantavirus
pulmonary Dengue
Syndrome
Marburg MDR/XDR tuberculosis Zika virus
Human Altican trypanosomiasie”chovora hemorthagis ever a
© Newly emerging © Re-emerging/resurging _@ “Deliberately emerging” The
New England
Journal of Medicine
Zika Virus in the Americas — Yet
Another Arbovirus Threat
AS Fauci and DM Morens Recently Emerging Human Arboviral
Diseases in the Americas
Dengue 1990s
West Nile 1999
Chikungunya 2013
Zika 2015
Yellow Fever 2016
Others: Bourbon, Cache Valley,
Heartland, Itaqui, Mayaro, Oropouche,
Powassan
Source: PF Vasconcelos & CH Calisher, Vector Borne Zoonotic Dis 16:295, 2016. Zika Virus Spread, 1947-2017
195: ee
First 44.1947:
human ‘Discovered
cases \}~) in’Uganda
described
<— French Polynesia
¢
Source: Lancaster University
+2013: > Brazil
}
¥ Suspected and Confirmed Zika Cases
in the Americas, 2015-2017
40,000
9 "=m Central America
$ 35,000 [== Caribbean
mmm South America
§
12527 2991 999537 90414945.474951 1 3 5 7 9 11191517 1921 282527 2951 3395979941 43454749511 9 5 7 911131517
2015 2016
Epidemiological week
2017
‘Source: PAHO, 5/25/2017. Symptoms of Zika Virus Infection
@ 4in 5 individuals asymptomatic
Incubation Mild symptoms
3-12 days 2-7 days
———Y }
Rash Headache/Malaise
Non-purulent conjunctivitis/
Conjunctival hyperemia
Elevated body temperature
(Above 99°F)
Arthralgia/Myalgia
) Peripheral edema/gastrointestinal
disturbance have also been observed
Source: BMJ.com, 2/2016 Marked Increase in Microcephaly
Cases in Brazil
Microcephaly cases in Brazil 2010-14;
suspected/confirmed cases 2015-2017
Associated Press oy 5,989
November 30, 2015
;
Brazil Links é
Mosquito-Borne B acc
Zika Virus to =
Microcephaly | * 265
Birth Defect contr
o 2010 2011 2012 2013 2014 2015-
17
Reporting year
“docs not include cases investgsted
alates
Source: Brazilian MOH; data as of April 26, 2017 Baby Born With Microcephaly
pe Congenital Zika Syndrome is a Pattern
of Birth Defects in Babies Infected with
Zika During Pregnancy
Damage to the brain
Small head size
(microcephaly)
Problems with vision
and hearing ponte
Problems with feeding
(difficulty swallowing)
Problems moving
limbs and body
Source: CDC Potential for Imported Cases of Zika
in the United States
H ~216 million
Passenger journeys
to U.S. annually
from areas with
local Zika virus
transmission
— 34M by air
- 173 M by land
-9M by sea
Sources: B Nelson et al. PLoS Currents Outbreaks, 6/31/2016; NY Times. Reported Cases of Zika Virus Disease
in the United States, 2015-2017
@ US. States / District of Columbia
- 5,053 travel-associated
- 224 locally acquired mosquito-borne
- 47 sexually transmitted
- 1 laboratory-acquired, 1 unknown
Hf U.S. Territories
- 36,467 locally acquired
- 143 travel-associated
“Excludes congenital cases ‘Source: CDC, data as of July 12, 2017 Reported Zika Cases are Likely a
Small Proportion of Actual Infections
in Puerto Rico
Kanye
cere ne |i ~ 469,321 Zika virus
Research infections
Use of Blood Donor April-August 2016,
Screening Data to 12.9% of population
Estimate Zika Virus
Incidence, Puerto Rico,
April-August 2016
MS Chevalier, MJ Kuehnert et al. Locally Acquired Mosquito-Borne Zika
Infections in Florida and Texas, 2016-2017
Palm Beach
7 County
— Broward
_ County
> Miami-Dade
ean - te
‘Source: CDC, data as of July 12, 2017 Zika-Affected Pregnancies and
Outcomes in the United States,
2015-2017
U.S. States / District of Columbia
- 1,687 completed pregnancies with or without birth defects
- 88 liveborn infants with birth defects
- 8 pregnancy losses with birth defects
Hf U.S. Territories
- 2,830 completed pregnancies with or without birth defects
- 122 liveborn infants with birth defects
- 6 pregnancy losses with birth defects
‘Source: CDC, data as of June 27, 2017 ened
‘isigns’
B In 2016, 10% of pregnant women in the U.S.
with confirmed Zika infection had a fetus or
baby (n=51) with birth defects
lm 15% of women infected in the first trimester
had an affected fetus or baby Therapeutics Novel Vector Control
NIH Zika
Countermeasure
Research and
Pere Cey Tutt §
Basic Research “= 7 ‘.
A .
\
Ss,
SRIVN Genomics fe B Research
Vaccines
Expansion of
Research
Capacity Therapeutics Novel Vector Control
NIH Zika
Countermeasure
Research and
Pere Cey Tutt §
Basic Research Expansion of
A ss Research
: Capacity
\ NWN
Ss,
6, { is y Clinical
'* Genomics NIH Zika Vaccine Candidates
@ DNA vaccine (NIAID VRC)
— Zika purified inactivated vaccine
(WRAIR/NIAID/BARDA and Sanofi Pasteur)
Live-attenuated Zika/dengue chimeric
virus (NIAID intramural/Butantan)
@ mRNA vaccine candidate (NIAID VRC,
GSK)
Vesicular Stomatitis Virus vectored
vaccine (NIAID extramural) NIH Zika Vaccine Candidates
— Zika purified inactivated vaccine
(WRAIR/NIAID/BARDA and Sanofi Pasteur)
Live-attenuated Zika/dengue chimeric
virus (NIAID intramural/Butantan)
@ mRNA vaccine candidate (NIAID VRC,
GSK)
Vesicular Stomatitis Virus vectored
vaccine (NIAID extramural) i) National Institutes of Health FOR IMMEDIATE RELEASE
Phase 2 Zika Vaccine Trial
Begins in U.S. and Central and
South America
Study Will Evaluate NIH’s
Experimental DNA Vaccine
Enrollment target: at least 2,490
individuals in the continental United
States, Puerto Rico, Brazil, Peru,
Costa Rica, Panama and Mexico Five Administrations and Emerging
Infectious Diseases
Ronald W. Reagan 1981 - 1989 George H.W. Bush 1989 - 1993
a
7 ia
William J. Clinton 1993 - 2001 George W. Bush 2001 - 2009
i
Barack H. Obama 2009 - 2017 Six Administrations and Emerging
Infectious Diseases
Ronald W. Reagan 1981 - 1989 George H.W. Bush 1989 - 1993
bo
OH
George W. Bush 2001 - 2009
cA
Barack H. Obama 2009 - 2017 Donald J. Trump 2017 - present What’s Next? Health Officials Brace for Return
| of Zika Global Examples of Emerging and
Re-Emerging Infectious Diseases
Antimicrobial- West Nile virus Cryptosporidiosis Ebola virus disease Dipht
resistant threats \° Powassan E col 7
Enterovirus Drug-resistant malaria //
CRE virus 104: Ha / Drug ay
MRSA \ 68, ‘ ‘ <
2G: diffcile
Ni. gonorrhoeae
HON2V inh
Cyclosporiasis — E. coll
E.coli O187:H7 —Z ovs7:H7
Measles: HiONa
Human — influenza
monkeypox —]
Listeriosis
Bourbon
virus | tence
2009 HIN:
influenza “\/ aa
Adenovirus 14% virus
Anthrax
bioterroniem “7 Henara
Chikungunya 7 Enterovirus 71
Hantavirus J Z juman monkeypox
Hantavirus’ Dengue aan SH Keyp
syndrome Zika virus Mf \ SS Ebola virus disease
Yellow fever /\|/7 Marburg MDR/XDR tuberculosis. Zika virus
Human African trypanosomiasis” Cholera hemorthagic fever Plague
© Newly emerging © Re-emerging/resurging @“Deliberately emerging” |... Five Waves of Human H7N9 Influenza
Infections in China, February 2013-present
140)
ae. __olllinon hy
BGT GOWNIZT 2345678 9IINI21 234567 89121294567 902129456
2013 2014 2015 2016 2017
Source: FAO, 7/1217
Number of humar
eS SSSS8 Global Examples of Emerging and
Re-Emerging Infectious Diseases
Antimicrobial- West Nile virus ___Cryptosporidiosis Ebola virus disease Diphtheria MERS-CoV
resistant threats * powassan E col 47 aehmeta virus
\ Enterovirus) Drug-resistant malaria //
CRE virus 104:H4 a / :
MRSA \_ 068. Z _ Rift Valley fever
“C. difficile Typhoid fever
fi. gonorrhoeae eee
HON2V inh bunyavirus
Cyclospor ss coll
E. coll 0187:H7 —Z — 6187:H7
Measles —-— HIONS
Human influenza
monkeypox —] aa
Listeriosis | influenza
Bourbon +
virus | nituenza
2009 HINt ‘SARS
influenza
Adenovirus 14 Nipan
Anthrax
bioterrorism Henara
Chikungunya, Enterovirus 71
Hantavins Dengue Human monkeypox
Syndrome Zika virus
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