Yellow Fever Lecture Ktes Harvard, 1963
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Evolution of public Health Administration v&&hods for Braventlon of Yellow Fever

See what is Yellow Fever?

Before 1900 -

(1) Quarantine

(2) Firing Cannon
(3) Flight

(4) Vaccine

Sanarelli (1897) Bacillus Icteroides (Wasdin and Gettings BBS confirmed 1839)
(4) Anti Amargl Serum (Monte. 1900)

(6) Havana - 1900 - Thorough cleaning of city - Havana - 1901
  (a) Attack on breeding places of all mosquitoes attack on infected adults.
  (b) Fumigation (s) of infected houses and
(c) isolation and screening of cases.

Gorgas surprised at success-credited victory to fumigation

Evolution of Public Health Methods in Prevention of Yellow Fever

(1) What 3s Yellow Fever?

   causation

   vector

   animal host

   clinicel

  pathology

  immunology

  epidemiology

  wave-like phenomenon

   like measles

But some endemic areas some enzootjc areas


distrSb&ion

Havana 1901 double victory Yellow fever and malaria (firsts)
Gorgas 1902:'; look foreward in the future to a time when yellow fever will
have disappeared entirely as a disease of mankindL"

Panama - repeated !Fumigation
(8) All houses Panama failed,Gorgas concentrated on anti-larval work

for yellow fever L

Separated yellow fever from malaria

Anophelines natural foci

v - artificial foci - artefacts never on ground - never in forests

in Americas -

Attack on u
             0s a WV  ' breeding very expensive - weekly inspection of every

building, house, yard, compound, and boat

Panama success; 0. Cruz - Rio de Janeiro

Liceaga Joe White

Overall Observation

(a) Reduction (not eradication) of v in large endemic centers
led to (i) Disappearance of yellow fever from endemic centers - rapid. (Ii)

disappearance of yellow fever from all of tributary areas - more slowly -
(x) epidemiology of control confirmed &-ies aegygf;b as only vector, man es

only victim
(b) Endemic centers were few and could be known by rapid surveys and consul-

tation with local physicians

1999 Gorgas reiterated belief in eradicability of yellow fever

Definition of eradfcation

1913-I4 Rose to Asia

Iby loI5 yellow p .evor commlrss$onIW C GorgEsJComitted to eradication of Y.F.


1916 swvoy Eduador Peru Colombis Venezuela and coast of Brazil -

Only endemic center was Guayaqull

Nogn 'ii introdirced vaccine

Program - Ecuador Peru Guatemala (Brazil) Honduras, ElSalvador Nicaragua and

iflexico - Bacaramanga Colombia - 8 countries succeeded - Brazil

Brazil - 1923

Endemic centers - capital cities North Brazil - Weekly visits each house

Pouring out water, removing trash, destroying containers, puncturing roof

gutters, fishing water jars and cisterns.

Rockefeller Foundation repeated experience of Corn. F. A. 1919-1922

1925 victory in sight - African -.S$udy beauno

1426 Revolution

1924 Virus to monkeys
19yf?28 Victory in sight
Lengthened cycle and attempt at v eradication

Rjo outbreak 1928

Widespread dessem:nation

3 gears to dominate

As we look back - first decade of Rockefeller Foundation work, including

Noguchi's results were a failure -

1928-29 Public Health Administration in Rio turned the page back to 1901 -
put faith in fumigation (flJt rather than (a)) Lost, almost a year -

Hindle and Aragao Vaccine 1930 - Rockefeller Foundation accepted yellow fever

as major commitment in Brazil - FLS in direct charge

Obvious that m EgressZon curve flattened (lengthened cycle gave

yellow fever in Recife 0.8 actually 26$)


Obvious that yellow fever regression to zero was only apparent.

FLS

Learn to think liite Mata mosquito

DecS.ded to make v, reports, the end product of yellow fever ex-

penditures as certifiable as the bank account.

New low level approach ties aggy&j. house capture yellow fever viserotomy

Aadesaeesnti eradication 1933 but viscerotomy already 1931 - endemic yellow

fever and jungle yellow fever

Endemic yellow fever liquidated 1934

Jungle yellow fever 1932 - 1933
Then 1934 to 1940 Wave;'r/accine 17 D 1936

Fch vaccine - Besis of choice

Mass vaccination     Small Pox

Eradication of &des aem - Spread of USA, etc.

Introduction of DDT

Local Resistance DDT

-2

Yaws

Small Pox

Malaria


Yellow Fever Lecture Notes - Harvard 2962
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Yellow Fever and Eradication concept
Bfg news in Yellow Fever

D.S. joins up in war against          3 questtons  !&at is Aedem?
F+adicstion?  Ye1 low Fever?
1.  what is S?
   3 slides - urban vector of yellow fever and ather vi.ruses

2.  Vhat is eradication?
Eradication is the most important justification of International health -

Evolution from notification and quarantine to

Eradication and ssaking out se&beds of Infection,

Yellow fever aided in discrediting Eradication; contributed greatly to
Rehabilitation.

What is FXadication?
Definition Ex radix
Eradication an absolute
Does not recur in absence of preventive measures unless reintroduced:
Local state national regional global

Eradicate Error
Eradicate hunger
Congenital syphj.lis

What fs Yellow Fever?
Yellow Fever - as human disease
Onset - fever headache
body pains - active congestion
nausea - anxiety
Fever and pulse disproportional

24 hour lull after 48 to 72 hours
fever, albuminuria -

passive congestion, hemorrhage
icterus, anuria
death - 4 to 7 days (Range 3 to 10)
Mortality 50 to 60% of clsssical cases
5 to lo % - mild cases          - Real mortality based on infection

Picture of Severe infection
followed by severe intoxication
Symptoms per se not diagnostic
Course and timing important.

Death or complete recovery - 2 slides pathology 2
Permanent immunity - no second attack

Epidemiological Dpta:
Short incubation period
Short period infectivity
no carrier state
No chronic cases


Vector wi - external incubation 9 to 12 days (Davis 4 days)
Infected for life - no transovarian infection -
Effective infection 6 weeks

Etiology
Small virus - not known to exist in nature except in unbroken chain of acute
vertebrate infections (Primates andmersurials) caused by bite of previously
infected mosquito vector.

First aebovirua - more intensive study than any other virus
     \
Monkeys Marsupials best prototype
Chick Embryos - Very young chicks
Mouse brain - tissue culture
Viscerotropic > Viscera -
Neurotropic  > C.N.  '- Yellow fever encephalitis may be fatal.
Different incubation periods

Virua variable in cultures
17 D vaccine mutant
(Non-reproducible)

All strains homologous1
Neutralization Test - in practice very reliable in spite of B. virus group overlap.

Distribution of endemic yellow fever
Before 1900
American 1900 to 1931   Slide America
Africa 1900 to 1931     Slide ACrica

Yellow fever as a Zoonosis Jungle Yellow Fever
Primary in primates of forest - Marsupials -
Man accidental infection - no different from &des m yellow fever

Hosts
All primates apparently hosts
When infected
Susceptibility series but susceptibility not correlated with enzootic efficiency -
Americas - cePus - spider  Some susceptible
howler - rzarmosets
Africa - Bush babies monkeys   Hone susceptible
Asia - Rhesus and Cynomologus  All SUsceptible

Vectors  (Eaemogogus spegaazini     3 slides 3
     (
Americas (       equinus
               mesodentutus
    ( Aedes welen=
    ( Sabethes chloropterus

Africa mfricu
    kdes s-

As?a Aedes albopictus

Enzoot,d_c and )  Same factors of relationship virus vector non-imnune host
Epir0o#tic   1  es govern endemic and epidemic mes aem human yellow fever,


Yellow fever distribution after 1932
   Americas     slide
   Africa      slide

Yellow fever and eradication
  Eradication concept after Pasteur
  Yellow Fever before 1900 - no cure, no prevention, safety in flight
  Mississippi Valley 1878
   US Yellow Fever Commission 1879
   Carlos Finlay    1881
   Reed et al      1900
  Gorgas Havana    1901
  US Army Commission
Key Center Eradication - s Reduction in large cities only
  Gorga s 1909
   Rockefeller Foundation chartered 1913
   Threat of Panama Canal

Rcckefeller Foundation Yellow Fever Eradication
   1915 - l925 success
  1925 Alrican Adventure
   1928 Pub - Virus to Asian Monkeys
         Transmission Non-s

But 1926 - military epidemic - surprise - led to attempt to eradication
      v Parahyba
  1928 - Rio de Janeiro
  1929 - Socorro and Guasapati
Yellow Fever 1928 - 1931    Slide

Recife 1729 - Not able to withstand Bombardment with virus

Situation Brazil end of 1?29
  Yellow fever program had failed!  Eradication concept discredited
                     w - 1930 missed
Why cause (1) Inadequate attack on ;;edes?
       (2)   Unknown mechanism of survival?

Both v and yellow fever virus survived below threshold of visibilityl

Reorganization:  FLS personally responsible - From the top
   FLS 3 months - maps, itinerary, routine oiling foci.
Learn to think like inspector SFA 52 - Explosion in Nichteroy
Search for low level incidence - lowering thresholds of visibility -
  (a) Viscerotomy for yellow fever
  (b) Adult captures for v

Results showed (a) Inadequate attack on m sea; but because of limited
  area of attack on v* not in Key Centers

With lowered thresholds Visibility
  (a>  1731 - Endemic silent yellow fever NE BR.
Key center method not applicable
  (b) 1932 - yell ow fever without Aedes aepva - Key

Center method not applicable
  1933 Jungle yellow fever Brazil, Bol., Colombia, Venezuela


  (c) 1933 - as sea disappears port cJtl:.es
Importance over shadowed by jungle yellow fever, etc.
Rockefeller Foundation Yellow Fever eradication then had failed because of
2 unkrmwn mechanisms of surv i.vail

Silent endemic yellow fever e" Laminated by village and rural snti-Aedss am
mea a'd.rea - the end of Awm yell.ow fever August 1934 b*ut not wadfated.

Roots of yellow fever infection in forests - 1.933
  How important is jungle yellow fever?
   What measures should be taken?

In spite of previous non-recognition
jungle yellow fever important in its own right - young mans 3?sease
the engaged young matis disease 1932 - Sta Crua de la Sierra - v
(Attacks both sexes and all ages among Indians $n forest
House and Work / Forest.
Attacks mostly adult men - lumber and chic&ros and materos
1934 - 1940 Cel. Ponce    7 slides
1935 - Teofile Qtoni
1936 - Figueira - Cambara
1938 - Infectious cases Rio
Retrospective - Rio 1928 - Socorro, Guasapati 1929.  Slide endemic area and towns

Not only was jungle yellow fever a threat to cities and towns but was important
for rural populations - no cure, no prevention - stay out of 3nfected forest
and starve. - Esti.mated 15000 cases Brazil 19381

Measures taken

(a) v eradication for ci.ties as permanent protection of entire
  urban populations

(b) Vaccination for individual protection - Rural populations

Vaccination First
  Finlay believed he was giving mild infections ! (Protected'did not protect;
                     ' infected)'
   Killed virus vaccine Rio - 1929
   Iater animal tests
   serum virus 1931
   modjfied viruses

tissue culture and serum - Heterologous Sera
Fch neurotropic - Svarification - Failed in Brazil
17-B 1936 - 1937 '5 slides
Use in field 1937 - 1942
Reduced antigenicity
Serum Hepatitis
Postvac Encephalitis

Post-Vat Encephalitis w-lth Fch Neurotropic vaccine Costa Rica 1951 Nigeria 1952

Choice of vaccines
Vaccination
   Americas - Rural areas - Travelers
   Africa - Urban and rural


s Eradication Second
   E adication not planned    Slide
   Careful administration
   Complete coverage
  Oiling of focf.
   Adult captures for missed mother foci

Eradication discredited 1929;recommendation to decentralize ,to local health units.

1934 proposal to eradicate   in Brazil

aaePv&J not yellow fever, focus of attack.
Cities h&d on monthly cycle - 3/4 men for suburbs.
  Peripheral expansion from each eradicated center (Soper's Law)
   Interior towns, villages, rural areas -
  Cities of South Brazil, f_ncluding Sao Paula, where yellowfever never occurred.
  Paraguay Bolivia, Peru, Colombia, Venezuela, Cuba USA

   1939 - Sfx states and Rio de Janeiro
   1941 - Brazilian objective eradication!
PABO 1942 - Bolivian resolution
   1946 - Reinfestation Brazil
PAHC 1947 - PAHO resolution Braejl
  Fjrst official international eradication program
  Brazil carried early load
Soper's Law of Peripheral Expansion of eradication effective internationally
as well as internally.

Yellow Fever Helps -

   Cistribution 1946 - 1953 1 slide
  k?J Panama  Gxico 1948-58 2 slide
I(751 (15) St.0 Domingo de lo8 Colorado 5 s1.1de.s
  dc> Trinidarl Caracas 1.954 -  3 slides Trinidad an3 Caracas first reports
     since 1911;  Long apparent absence t1o index of safety
Id{ j to 8 countries each yr.   4 slides

      e  Since eradicatfon 1947 resolution all countries on the mafnland except
     Canada, USA, El Salvador, Chile Uruguay

DDT eases loedjresistancs of qLedes em

Scper's Law - Against USA 1954 - even though not of primary concern - Slide
19% Aedes situation.
   1958 -'Brazil 1942
   1959-1950 - &xico

Mexico 1961 five year limit

1962 US joins up.

US decision - not based on increased threat Yellow Fever, Dengue, encephalitis
and other viruses; but based on recognition of right of other nations which
have eradicated u to be protected against reinfestatfon from our
cities and ports.

New principle in International Health practicebUS joined in 5 year vote in
1962 against 2 laggard American nations in Sma 1 1 Pox eradication.

By-products of m eradication
An+&e$e~&~i.,$kasil 1939140 - missed in 1930-31


Rehabilitation of eradicotfon concept
  1947 US National Malaria Eradication Program
  1950 PAHO Kalaria, Yews, Small. Pox

hter `WHO Malaria, Yars Small Pox

1955 APHA endorsed eradication concept

USA - Poliomyelitis, Liohtheria, Tetanus, Whooping Cough (As Public Health
problems! But experic:.;ce will teach.)
Tuberculosis Syphilis

We learned from v and yellow fever
  (a) To lower threshold of visibility
  (b) to refine methods as zero is approached
  (c) the need for careful administration, meticulous checking, based on
    detailed records and complete coverage
  (d) the growth power of eradication through peripheral expansion.

Eradication is an increasingly useful concept as world shrinks and as Pan Am
and World Health Organizations become more adept at coordinating preventive
programs in all the countries of a region.

Just as part of a coluntry cannot enjoy t'ne benefits of oradfcatioc apart
from other units, so no $2ogle country may safely relax to enjoy its own
eradication efforts, so lung as eradication has not betin -extended to those
countries from which reinfection or reinfestatjon may come.

Yellow Fever in Africa vs Yellow Fever in AmerJ.cs   5 cycle sl4.des

Aedes in Americas domestlc
   Africa domestic and forest -
  Prospect for eradicationof
  m (Stegomyia) WzQ
  Human to Human Vector in;trtllages close to forest

Africa no m outbreaks in seutra1 and Eastern Africajno virus to Azfa.
FLY visit to S&an 1936
  Large outbreak in Sudan  Slide,  Afr",ca er,dcmlc
   194C-
   Ethiopia - 1959-60-61 62 - Slmpsoni.?

Still unknowns inyellow fever

Threat to Asia - greatly reduced in absence cf v in proxim-lty
to Infected forests.  (No urban yellow fever in central and Eastern Africa)

Monkeys succeptible - vectors available

Eradication of Aedes m Jn Asia
Final slide.            - he-rro~r-l;sdjc;isease jr. 1&>?1 la and Bangkok. -