Yellow Fever Lecture Notes Harvard, 1963 Evolution of Public Health Administration Methods for Prevention of Yellow Fever See what is Yellow Fever? Before 1900 - (1) Quarantine (2) Firing Cennon (3) Flight (4) Vaccine Sanarelli (1897) Bacillus Icteroides (Wasdin and Gettings PHS confirmed 1899) (4) Anti Amaryl Serum (Monte. 1900) (6) Havane - 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 is Yellow Fever? causation vector animal host clinical pathology immunology epidemiology wave-like phenomenon like measles i? But some endemic areas some enzootic areas vy ~ distribution Havana 1901 double victory Yellow fever and malaria (firsts) it Gorgas 1902!I look foreward in the future to a time when yellow fever will J have disappeared entirely as a disease of mankindw Panama - repeated fumigation (s) All houses Panama failed, Gorgas concentrated on anti-larval work Aedescaegypti for yellow fever - Separated yellow fever from malaria Anophelines natural foci Aedes segypti - artificial foci ~ artefacts never on ground - never in forests in Americas - Attack on Aedes aegypti 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 Aedes segypti in large endemic centers led to (4) 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 Aedes aegypti as only vector, man as only victim (b) Endemic centers were few and could be known by rapid surveys and consul- tation with local physicians 1909 Gorgas reiterated belief in eradicability of yellow fever Definition of eradication 1913-14 Rose to Asia Mey 1915 yellow fever commission, W C Gorges. Committed to eradication of Y.F, 1916 survey Eduador Peru Colombis Venezuela and coast of Brazil - Only endemic center was Guayaquil Nogu hi introduced vaccine Program - Ecuador Peru Guatemala (Brazil) Honduras, ElSalvador Nicaragua and Mexico - 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 Com. F. A. 1919-1922 1925 victory in sight - African - Study begune 15926 Revolution 1924 Virus to monkeys 199 N28 Victory in sight Lengthened cycle and attempt at Aedes gegypti eradication Rio outbreak 1928 Widespread dessemination 3 years 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 (flit rather then (s)) 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 dedes gegypti egression curve flattened (lengthened cycle gave yellow fever in Recife 0.8 actually 262) Obvious that yellow fever regression to zero was only apparent. FLS Learn to think like Mata mosquito Decided to make Aedes sgegyptj reports, the end product of yellow fever ex- penditures as certifiable as the bank account. New low level approach Aedes segypti house capture yellow fever vieerotomy Sedes aegypti 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 Waves Vaccine 17 D 1936 Fch vaccine - Basis of choice Mass vaccination Small Pox Eradication of Aedes aegypti - Spread of USA, etc. Introduction of DDT local Resistance DDT Anopheles. gambise Yaws Small Pox Malaria Yellow Fever Lecture Notes - Harvard 1962 Yellow Fever and Eradication concept Big news in Yellow Fever U.S. joins up in war against Aedes segypti 3 qnestions What is Aedes Aegypti? Eradication? Yellow Fever? 1. Wheat is Aedes aegypti? 3 slides - urban vector cf yellow fever end dher viruses 2. What is eradication? Eradication is the most important justification of International Health - Evolution from notification and quarantine to Eradication snd seeking out seedbeds of infection. Yellow fever aided in discrediting Eradication; contributed greatly to Rehabilitation. What is Eradication? Definition Ex radix Eradication an ebsolute Does not recur in absence of preventive messures unless reintroduced: Iocal state national regional global Eradicate Error Eradicate Hunger Congenital syphilis What is 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 veath - 4 to 7 days (Range 3 to 10) Mortality 50 to 60% of classical cases - Real mortality based on infection 5 to lo @ - mild cases Picture of Severe infection followed by severe intoxication Symptoms per se not diagnostic Course and timing impertant. Death or complete recovery ~ 2 slides pathology 2 Permanent immunity - no second attack Epidemiological Deta: Short incubation period Short period infectivity no carrier state Nc chronic cases Vector Aedes segypti - 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 andmarsurials) caused by bite of previously infected mosquito vector. First arbovirus -\more intensive study than any other virus Monkeys Marsupials\ best prototype Chick Embr'yos - Very young chicks Mouse brain - tissue culture Viscerotropic ) Viscera - Neurotropic )C.N. - Yellow fever encephalitis may be fatal. Different incubation periods Virus variable in culturee 17 D vaccine mutant (Non-reproducible) All strains homologous! Neutralization Test - in practice very reliable in spite of B. virus group overlap. Distribution of endemic yellow fever Before 1906 American 1900 to 1931 Slide America Africa 1900 to 1931 Slide Africa Yellow fever as a Zoonosis Jungle Yellow Fever Primary in primates of forest - Marsupials - Man accidental infection - no different from Aedes segypti yellow fever Hosts All primates apparently hosts When infected Susceptibility varies but susceptibility not correlated with enzootic efficiency - Americas - cetus ~ spider Some susceptible howler - marmosets Africa - Bush babies monkeys None susceptible Asia - Rhesus and Cynomologus 411 susceptible Vectors (HEaemogogus spegazzini 3 slides 3 equinus Americas ( mesodentutus ( Aedes aucocelenus ( Sabethes chloropterus Africa Aedes africanus Aedes simpson} Asta Aedes albopictus Enzootic and } Same factors of relationship virus vector non-immune host Epizooatic ) es govern endemic and epidemic Sedes aegypti human yellow fever, Yellow fever distribution after 1932 Americas slide Africa slide Yellow fever end eradicaticn 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 - Aedes aegypti Reduction in large cities only Gorgas 1909 Rockefeller Foundation chartered 1913 Threat of Panama Canal Reckefeller Foundation Yellow Fever Eradication 1915 - 1925 success 1925 ATrican Adventure 1928 Pub - Virus to Asian Monkeys Transmission Non-Aedes aegupti But 1926 - militery epidemic - surprise - led to attempt to eradication e Parahyba 1928 - Rio de Janeiro 1929 - Secorro and Guasapati Yellow Fever 1928 - 1931 Slide Recife 1929 - Not able to withstand Bombardment with virus Situation Brazil end of 1929 Yellow fever program had failed! Eradication concept discredited Anopheles gambise - 1930 missed Why cause (1) Inadequate attack on Aedes segypti? (2) Unknown mechanism of survival? Both Aedes aegypti and yellow fever virus survived below threshold of visibility! 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 Aedes aegypti Results showed (a) Inadequate attack on Aedes segypti; but because of limited area of attack on Aedes segypti, not in Key Centers With lowered thresholds Visibility (a) 1931 - Endemic silent yellow fever NE BR. Key center method not epplicable (bo) 1932 = yellow fever without Aedes aegypti - Key Center method not applicable 1933 Jungle yellow fever Brazil, Bol., Colombia, Venezuela (c}) 1933 - Aedes segypti disappears port cities Importance over shadowed by jungle yellow fever, etc. Rockefeller Foundation Yellow Fever eradication then had failed because of 2 unknown mechanisms of survivail Silent endemic yellow fever eliminated by village and rurel anti-Aedes aecvpti Measures - the end of Aejes aegypti yellow fever August 1934 but not aradicated. Roots of yellow fever infection in forests - 1933 How important is jungle yellow fever? What measures shoulc be taken? In spite of previous non-recognition jungle yellow fever important in its own right - young mans jisease the engaged young mans disease 1932 - Sta Cruz de la Sierra - Aedes aegypti (Attecks both sexes and all ages among Indians in forest House and Work / Forest. Attacks mostly adult men - lumber and chiclsros and materos 1934 - 1940 Cel. Ponce 7 slides 1935 - Teofile Otoni 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 infected forest and starve. - Estimated 15000 cases Brazil 1938! Measures taken (a) Aedes aegypti eradication for cities 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 later animal tests serum virus 1931 modified viruses tissue culture and serum - Heterologous Sera Feh neurotropic - Sy@rification - Failed in Brazil 17-D 1936 - 1937 5 slides Use in field 1937 - 1942 Reduced antigenicity Serum Hepatitis Postvae Encephalitis Post-Vac Encephalitis with Feh Neurotropic vaccine Costa Rica 1951 Nigeria 1952 Choice of vaccines Vaccination Americas - Rural areas - Travelers Africa - Urban and rural Aedes gegypti Eradication Second E adication not planned Slide Careful administration Complete coverage Oiling of foci Adult captures for missed mother foci Eradication discredited 1929" recommendation te decentralize to local health units, 1934 proposal to eradicate in Brazil hedes asepypti, not yellow fever, focus of attack. Cities held 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, including Sao Paulo, where yellow fever never occurred. Paraguay Bolivia, Peru, Colombia, Venezuela, Cuba USA 1939 + Six states and Rio de Janeiro 1941 - Brazilian objective eradication! PAHO 1942 - Bolivian resolution 1946 ~ Reinfestation Brazil PAHO 1947 - PAHO resolution Brazil First 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 ~ Distribution 1946 - 1953 1 slide (2) Panama Mexico 1948-58 2 slide 1951 (b) Sto Domingo de los Colorado 3 slides (c) Trinidad Caracas 1954 - 3 slides Trinidad and Caracas first reports Since 1914 Long apparent absence no index of safety (3) 5 to 8 countries each yr. 4 slides (e) Since eradication 1947 resolution all countries on the mainland exceot Canada, USA, £1 Salvador, Chile Uruguay DDT eases loadjresistance of Aedes aegypti - Scper's law - Against USA 1954 - even though not of primary concern - Slide 1956 Aedes aegypti situation. 1958 — Brazil 1942 1959-19650 - Mexico 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 Aedes aegypti to be protected against reinfestation from our cities and ports. New principle in international Health practice+US joined in 5 year vote in 1962 against 2 laggard American nations in Sma41 Pox eradication. By-products of Aedes aegypti eradication Anopheles gambiaweazil 1939/40 - missed in 1930-31 Et ia 3 Rehabilitation of eradication concept 1947 US National Malaria E,adication Program 1950 PAHO Malaria, Yews, Small Pox later WHO Malaria, Yaws Small Pox 1955 APHA endorsed eradication concept USA - Poliomyelitis, Lightheria, Tetanus, Whooping Cough (As Public Health problems! But experie:ce will teach.) Tuberculosis Syphilis We learned from Aedes aegypti 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 st coordinating preventive programs in all the countries of a region. Just as part of a country cannot enjoy the benefits of eradication apart from other units, so no single country may safely relax to enjoy its own eradication efforts, so lung as eradication has not been axtended to those countries from which reinfection or reintestation may come. Yellow fever in Africa vs Yellow Fever in Americe 5 cycle slides Kedes aegypti in Americas domestic Africa domestic and forest - Prospect for eradication of Aedes aegypti in Africa? Aedes (Stegomyia) sinpsoni, , Human to Humen Vector invvtllages close to forest Africa no Medes eegypti outbreaks in central and Eastern Africa: no virus to Agia. FLS visit to Sudan 1936 } large outbreak in Sudan Slide. Africa endemic. 1940- Ethiopie - 1959-60-61 62 - Simpsoni? Still unknowns in yellow fever Threat to Asia - greatly reduced in absence of Aedes segypti in proximity to infected forests. (No urban yellow fever in centrel and Festern Africa) Monkeys succeptible - vectors available Eradication of Aedes aegypti in Asia - herrorriagitdisease jn en: la and Bangkok. - Final slide.