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"In the interest of humanity and the cause of science": the yellow fever volunteers.

The scientific discoveries of the U.S. Army Yellow Fever Board of 1900 are well known as are the Army physicians who led the board. Walter Reed, of course, is the best known, but James Carroll, Aristides Agramonte, and Jesse Lazear are also known, if not nationally, to their local communities. This article deals not with the known but with the unknown, meaning the volunteers who subjected themselves to the ravages of yellow fever and the real possibility of death. The year 1900 was known as a "yellow fever year" among the locals in Cuba because in the preceding year the epidemics had been relatively mild. Beginning its work in June 1900 in the midst of a deadly epidemic, the board conducted a truly remarkable set of experiments that set a benchmark for controlled clinical trials and informed consent. Because no animal model was known to be susceptible to yellow fever, they used human volunteers for their experiments. These volunteers were recruited from among Spanish immigrants and were accepted from soldiers and two civilians who volunteered. Over 30 men participated in the experiments, and 22 developed yellow fever. With expected death rates of 20% to 40%, it is incredible that none of these volunteers died. In 1929, the U.S. government honored the Americans who volunteered by placing their names on a Roll of Honor published annually in the Army Register. The successes of the 1900 U.S. Army Yellow Fever Board were truly remarkable, and many of the successes were made possible by the men who volunteered, some repeatedly, to risk their lives "in the interest of humanity and the cause of science."

Awards and Prizes↗

Carlos Finlay and yellow fever: triumph over adversity.

The eradication of yellow fever in Havana, Cuba, was achieved by a fruitful collaboration between American and Cuban physicians. Carlos Finlay, a Cuban physician who proposed the mosquito-vector theory in 1881, shared his ideas, his publications, and a sample of mosquito eggs with the U.S. Army Yellow Fever Commission. The commission, headed by MAJ Walter Reed, used human volunteers to confirm Finlay's theory. MAJ William Gorgas adopted mosquito-control measures in his sanitation program and, within 6 months, yellow fever was controlled in Havana for the first time. Finlay held fast to his ideas despite incredulity and ridicule. His tenacity and scientific honesty vindicated his ideas about yellow fever.

Animals↗

[Yellow fever in Venezuela].

In Venezuela the yellow fever has been presented in three wild focuses: San Camilo in the Tachira State, South of the Lake in the Zulia and Guayana. The last human case registered of urban yellow fever happened in 1918 in the city of Coro, Falcon State. Nevertheless, according to the epidemic registration of the Ministry of Health and Social Development corresponding to the epidemiological week no. 38 of the year 2003, 318 cases of wild yellow fever had been investigated (173 of the Zulia and 145 of Tachira), of which were confirmed 31, with a mortality of 58.0%. Previous to the appearance of this outbreak, it was notified an epizooty in monkeys with high mortality in November of 2002 in the Jesus Maria Semprum municipality of the Zulia State, persisting until September of 2003, extended to the Tachira State. Possible reasons of the reemergency of this illness are analyzed based on the high mobilization of displaced population, remote areas and of difficult access, high concentration of indigenous population (Bari, Yuepa, Wayúu) and border conflict.

Humans↗

Heparan sulfate-mediated binding of infectious dengue virus type 2 and yellow fever virus.

Dengue virus type 2 and Yellow fever virus are arthropod-borne flaviviruses causing hemorrhagic fever in humans. Identification of virus receptors is important in understanding flavivirus pathogenesis. The aim of this work was to study the role of cellular heparan sulfate in the adsorption of infectious Yellow fever and Dengue type 2 viruses. Virus attachment was assessed by adsorbing virus to cells, washing unbound virus away, releasing cell-bound virus by freezing/thawing, and then titrating the released infectious virus. Treatment of cells by heparin-lyase, desulfation of cellular heparan sulfate, or treatment of the virus with heparin inhibited cell binding of both viruses. Heparin also inhibited Yellow fever virus infection by 97%. Using infectious virus, the present work shows the importance of heparan sulfate in binding and infection of these two flaviviruses.

Adsorption↗

South Carolina's last yellow fever epidemic: Manning Simons at Port Royal, 1877.

Throughout the 19th century, yellow fever was the scourge of southern coastal cities. Because of primitive diagnostic tools, differential diagnosis during epidemics was often difficult. Many patients were diagnosed with "malarial fever," breakbone fever, "the prevailing fever," and "mild yellow fever," to name a few. Dr. Manning Simon's opportunity to study an almost "pure" epidemic of yellow fever among an "unacclimated" population was a breakthrough in diagnostic medicine. Fortunately, his findings were not to be needed again in South Carolina, since this was the last outbreak of yellow fever in the state.

Disease Outbreaks↗

Yellow Fever Immunizations: Indications and Risks.

The yellow fever vaccine plays an essential role in protecting humans from yellow fever, and millions of doses are administered each year. The attenuated live-virus vaccine has long been considered to be among the safest and most effective vaccines. Newly recognized rare, but sometimes fatal, adverse events associated with the vaccine have prompted scrutiny of the traditional recommendations for use of the vaccine and have raised questions about their pathogenesis. This paper describes the adverse events associated with the vaccine, reviews postulated reasons for the recent recognition of these events, discusses key research questions that need to be addressed in trying to understand their origin and risk factors, and reviews current indications for the use of the vaccine. Knowledge of the epidemiology of yellow fever is necessary to make informed recommendations. Current surveillance is inadequate to provide a precise exposure risk for most travelers.

Journal Article↗

Antibody response to 17D yellow fever vaccine in Ghanaian infants.

OBJECTIVES: To assess the seroresponses to yellow fever vaccination at 6 and 9 months of age; assess any possible adverse effects of immunization with the 17D yellow fever vaccine in infants, particularly at 6 months of age. METHODS: Four hundred and twenty infants who had completed BCG, OPV and DPT immunizations were randomized to receive yellow fever immunization at either 6 or 9 months. A single dose of 0.5 ml of the reconstituted vaccine was administered to each infant by subcutaneous injection. To determine the yellow fever antibody levels of the infants, each donated 1 ml whole blood prior to immunization and 3 months post-immunization. Each serum sample was titred on Vero cells against the vaccine virus. FINDINGS: The most common adverse reactions reported were fever, cough, diarrhoea and mild reactions at the inoculation site. The incidences of adverse reactions were not statistically different in both groups. None of the pre-immunization sera in both age groups had detectable yellow fever antibodies. Infants immunized at 6 months recorded seroconversion of 98.6% and those immunized at 9 months recorded 98% seroconversion. The GMT of their antibodies were 158.5 and 129.8, respectively. CONCLUSIONS: The results indicate that seroresponses to yellow fever immunization at 6 and 9 months as determined by seroconversion and GMTs of antibodies are similar. The findings of good seroresponses at 6 months without significant adverse effects would suggest that the 17D yellow fever vaccine could be recommended for use in children at 6 months in outbreak situations or in high risk endemic areas.

Antibodies, Viral↗

Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002.

This report updates CDC's recommendations for using yellow fever vaccine (CDC. Yellow Fever Vaccine: Recommendations of the Advisory Committee on Immunizations Practices: MMWR 1990;39[No. RR-6]1-6). The 2002 recommendations include new or updated information regarding 1) reports of yellow fever vaccine-associated viscerotropic disease (previously reported as febrile multiple organ system failure); 2) use ofyellow fever vaccine for pregnant women and persons infected with human immunodeficiency virus (HIV); and 3) concurrent use of yellow fever vaccine with other vaccines. A link to this report and other information related to yellow fever can be accessed at the website for Travelers' Health, Division of Global Migration and Quarantine, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/travel/index.htm, and through the website for the Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/ncidod/ dvbid/yellowfever/index.htm.

Adolescent↗

Imported yellow fever in a United States citizen.

The last imported case of yellow fever seen in this country was in 1924. We report a case of yellow fever acquired by an American tourist who visited the jungles of Brazil along the Rio Negro and Amazon Rivers. The patient died 6 days after hospital admission and 10 days after his first symptoms appeared. Yellow fever virus was recovered from clinical specimens, and the isolate was genetically similar to the E genotype IIB of South American yellow fever viruses. This patient's illness represents a case of vaccine-preventable death since he failed to be immunized with a recommended preexposure yellow fever vaccine.

Animals↗

Urbanisation of yellow fever in Santa Cruz, Bolivia.

BACKGROUND: Reinvasion by Aedes aegypti of cities in the Americas poses a threat of urbanisation of yellow fever. After detection of yellow-fever infection in a resident of the city of Santa Cruz, Bolivia, in December, 1997, we investigated all subsequent suspected cases. METHODS: We introduced active surveillance of yellow fever in the Santa Cruz area. Hospitals and selected urban and rural health centres reported all suspected cases. Patients were serologically screened for yellow fever, dengue, hepatitis A and B, and leptospirosis. We collected clinical and epidemiological information from patients' records and through interviews. We also carried out a population-based serosurvey in the neighbourhood of one case. FINDINGS: Between December, 1997, and June, 1998, symptomatic yellow-fever infection was confirmed in six residents of Santa Cruz, five of whom died. Five lived in the southern sector of the city. Two had not left the city during the incubation period, and one had visited only an area in which sylvatic transmission was deemed impossible. Of the 281 people covered in the serosurvey 16 (6%) were positive for IgM antibody to yellow fever. Among five people for whom this result could not be explained by recent vaccination, there were two pairs of neighbours. INTERPRETATION: Urban transmission of yellow fever in Santa Cruz was limited in space and time. Low yellow-fever immunisation coverage and high infestation with A. aegypti in the city, and the existence of endemic areas in the region present a risk for future urban outbreaks. We recommend immediate large-scale immunisation of the urban population, as well as tightened surveillance and appropriate vector control.

Adult↗

Epidemic yellow fever in eastern Nigeria, 1986.

An epidemic of yellow fever occurred in the eastern part of Nigeria during the second half of 1986. Oju, in Benue State, was the most heavily affected region, but yellow fever also occurred in surrounding areas, particularly Ogoja, in Cross River State. In Oju, the mean attack and mortality rates were 4.9% and 2.8%, respectively. Sex and age specific rates were highest in males and in the 20-29 yr age group. The overall case fatality rate was approximately 50%. Diagnosis was confirmed by IgM capture enzyme-linked immunosorbent assay (ELISA) and complement fixation (CF) tests. Entomological investigations implicated Aedes africanus as the epidemic vector. Oju alone probably had about 9800 cases of yellow fever with jaundice, and some 5600 deaths. Outbreaks of this nature could be prevented by inclusion of yellow fever in the Expanded Programme on Immunisation, in areas subject to recurrent epidemics.

Adolescent↗

Yellow fever vaccine-associated viscerotropic disease and death in Spain.

Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a recently described severe adverse event after yellow fever vaccination, and some cases have been reported in different countries [Anonymous. Effects of yellow fever and vaccination. Lancet 2001;358(9296):1907-9]. Herein we describe a YEL-AVD case in a young woman, who died after vaccination with 17D-204 strain. Clinical, serological and immunochemical analysis as well as virus detection, quantification, sequence analysis and cytokine release, were performed. Further investigations on yellow fever vaccine adverse events, and carefully analysis of the immune response elicited are important tasks for the future.

Adult↗

[Yellow fever].

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Biometry↗

Yellow fever haemagglutination-inhibiting, neutralising and IgM antibodies in vaccinated and unvaccinated residents of Ibadan, Nigeria.

A survey for yellow fever virus haemagglutination inhibiting (HI) and neutralising (N) and IgM antibodies was carried out in unvaccinated people in Ibadan and in those immunised with the yellow fever 17-D vaccine. A total of 207 people were tested for HI antibody to yellow fever and two other flaviviruses namely: Wesselsbron and Uganda S. viruses. Prevalence of HI antibody to each flavivirus antigen was as follows: Yellow fever 26%, Wesselsbron 18% and Uganda S 33%. Of the 207 people, 37 (18%) had yellow fever N antibody. There was a higher prevalence of N antibody to yellow fever virus in adults than children. Twenty-one people vaccinated with 17-D yellow fever vaccine donated post-vaccination sera; 10 (48%) had no prevaccination HI antibody, 7 (33%) had HI antibody to one flavivirus and 4 (19%) to two or more flaviviruses. Ninety percent of seronegative people and all those with prevaccination flavivirus antibodies developed HI or N antibody, following vaccination. A total of 58 unvaccinated people were tested for yellow fever IgM antibody by an enzyme linked immunosorbent assay, 2 (3%) were positive; suggesting that active yellow fever transmission was in progress at the time of survey.

Adolescent↗

[Culicidae insect fauna from rural zone in Amazonas State with incidence of sylvatic yellow fever].

After the occurrence of 14 sylvatic yellow fever cases in 10 cities in the State of Amazonas during 1996, an investigation into the presence of sylvatic yellow fever vectors was carried out. The material of larvae and adult insects was collected around residences and canopy trees within forests, using a light trap (CDC) and human bait. A total of 424 insects was collected. Thirty seven species were identified, some of which were sylvatic yellow fever vectors: Haemagogus janthinomys, Ha. leucocelaenus, Aedes fulvus.

Animals↗

Skin reaction to yellow fever vaccine after immunization with rabies vaccine of chick embryo cell culture origin.

Skin reaction to yellow fever vaccine was examined after immunization with rabies vaccine. The two vaccines contained substrates from chick embryo cells (rabies vaccine) and chick whole embryo (yellow fever attenuated vaccine), as well as gelatin. A prick test with gelatin showed negative results in all vaccinees examined. An intradermal skin test revealed that the yellow fever vaccine had reacted with an anti-egg protein antibody-like substance in a case with a history of egg allergy before rabies vaccination. A case inoculated two times with the rabies vaccine revealed a positive reaction to egg-white protein as well as the yellow fever vaccine. This case had no anamnesis of egg allergy. Thus, an antibody reactive to the egg-white protein and/or the yellow fever vaccine was inducible by the rabies vaccine. The reaction of this antibody was not systemic but local at the skin test by the yellow fever vaccine. The period of the rabies vaccine sensitization reactive to the yellow fever vaccine could be estimated as longer than 14.3 +/- 9.6 days (mean +/- SD), based on a follow-up examination of the positive skin reaction in 41 of 84 cases examined. We therefore conclude that the yellow fever vaccine can be safely administered at an interval of at least four weeks after a second rabies vaccination.

Adult↗

Neutralizing and haemagglutination-inhibiting antibodies to yellow fever 17 years after vaccination with 17D vaccine.

The duration of immunity conferred by yellow fever vaccine is as yet undetermined. In this study the neutralizing and haemagglutination-inhibiting antibodies to yellow fever were investigated in 108 persons living in Pouso Alegre, Brazil, where yellow fever has never been reported. These persons had been vaccinated with 17D yellow fever vaccine between 27 December 1940 and 5 February 1941, but not again; and their antibody pattern was compared with that of 78 controls who had never been vaccinated. In the vaccinated group the majority had neutralizing and haemagglutination-inhibiting antibodies present in the serum, whereas in the unvaccinated group antibodies were all but completely absent. Heterologous antibodies to other viruses of Casal's Group B were also found, and the significance of this finding is discussed.

Antibodies↗

[Poison and the mosquito: epistemological aspects of the etiology and prophylactics of yellow fever].

The strategies against yellow fever developed by Argentina and Brazil were discussed at the Second Medical Congress of Latin America which was held in Buenos Aires in 1904. The study of the controversy between physicians from Argentina and Brazil around the existing explanatory models of this illness and the international prophylactic strategies in use at the time enables an epistemological understanding of the breakthrough brought about by the emergence of medicine of vectors. This chapter of Latin American medicine history constitutes a unique opportunity to analyze that reorganization of knowledge, which permitted the inclusion of intermediary living beings into the medical and epidemiological discourse.

Animals↗