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In October 1899, Prof. Eduardo Chapot-Prévost suggested to the minister of Justice and Internal Affairs, Epitácio Pessoa, that Oswaldo Cruz be included on the medical commission set to travel to the port of Santos, on the São Paulo coast, to ascertain whether the deaths of massive numbers of rats in that region had anything to do with the bubonic plague. The epidemic had been diagnosed by Vital Brazil and Adolfo Lutz, assistant physician and director of the Bacteriological Institute of São Paulo, respectively. Their diagnosis had been questioned by part of the press and local merchants and was also stirring controversy among the city’s doctors.

Cruz arrived in Santos on October 22, 1899. After five days of nonstop work, he confirmed the epidemic. He accidentally contaminated himself with the plague while there, but thanks to serum did not develop the disease. Vital Brazil, however, was not as lucky; his friend Cruz cared for him when he fell ill.

At that time, the only treatment available for the plague was serum therapy, and the Pasteur Institute in Paris was the only place that produced serum and vaccine for the disease. In light of this, the sanitary authorities in São Paulo and the Federal District decided to set up their own serum therapy institutes. A laboratory attached to the Bacteriological Institute was established in the capital of São Paulo, later transformed into the Butantan Institute. The Federal Serum Therapy Institute—often referred to as Manguinhos Institute—was founded in the Brazilian capital. The government appointed the Baron of Pedro Afonso, owner of the Municipal Vaccine Institute, to head the institute in Rio.

With the Baron in charge, and staffed by a group comprising Cruz, physician Henrique Figueiredo de Vasconcelos, and the students Antônio Cardoso Fontes and Ezequiel Dias, the Federal Serum Therapy Institute began operations on May 25, 1900. Five months later, the government received the first hundred vials of plague vaccine and sera made by the institute.

A municipal vaccination post for the plague was inaugurated at the Botafogo Polyclinic the following year. This institution would leave an imprint on Cruz’s life for another reason as well: it was there that the sanitarian did his first research on yellow fever.