The forgotten tale of Brazilian phage therapy

Abstract

The use of bacteriophages to treat bacterial infections (phage therapy) is considered a possible solution to the antimicrobial resistance crisis. However, phage therapy is not a new concept. The discovery of phages in the early twentieth century was closely tied to clinical practice, and phage therapy quickly spread around the world.The use of phage therapy in twentieth century South America is still shrouded in mystery and has been mentioned only briefly in recent scientific literature. Research on Brazilian reference collections of medical texts revealed that Brazil was an important, but so far little-known, player of phage therapy, uncovers interesting priority claims and missing pieces of phage therapy history. Of note, there is the widespread use of phages against bacillary dysentery and staphylococcal infections, with Dr José da Costa Cruz from the Institute Oswaldo Cruz as Brazil's leading expert and pioneer. This review about historical phage use in a South American country fills gaps in our knowledge about the "golden years" of phage therapy, providing information about successful experiences that can be useful against dangerous pathogens in our time. Key points• Brazil had an important role in the golden years of phage therapy, which lasted until the mid-twentieth century.• Dr José da Costa Cruz from the Institute Oswaldo Cruz in Rio de Janeiro was the leading expert.• The first phage therapy cases in Brazil took place in 1921 during an outbreak of dysentery in Barbacena.• The mass testing of the Institute Oswaldo Cruz phage product during the Paulista revolution of 1924 preceded Dr d'Herelle's tests in India and the Soviet Union's tests on military troops.• Successful phage use in Brazil was against bacillary dysentery and staphylococcal infections.• The available information about phage therapy clinical cases and phage products was retrieved from the literature investigated and presented in this publication. Research in contextEvidence before this study Reports summarising the use of phage therapy in Brazil were scarce before this review. Only three recent publications mentions, briefly and without details, that Brazilian doctors were involved with phage therapy in the 1920s. Sixteen sources of Brazilian medical publications were checked for phage-related information, looking at the period from 1915 (when Dr Frederik Twort published his phage discovery) to 1952. Any phage or phage therapy related words in titles and abstracts were used as inclusion criteria. The risk of bias associated with data inclusion is minimal, because the objective was to have all published material concerning phages.However, since routine phage therapy cases were not always published, the data presented here are probably only a fraction of the actual phage use at the time.

Strategies for Surface Immobilization of Whole Bacteriophages: A Review

“…Bacteriophages were independently discovered by microbiologists Frederick Twort in London in 1915 and by Felix d'Herelle in Paris in 1917 6 .It should be noted that extensive research on phage phenomena was also carried out in Poland during the interwar period 7 , as well as in Brazil. Indeed, the oft-cited pioneering 1919 work by d'Hérelle in the use of phage to treat dysentary in French soldiers was followed relatively soon afterwards by similar trials in 1923 in both Poland 7 and Brazil 8 . Such research eventually led to the widespread use of phages in the Soviet Union for the treatment of routine bacterial infections, with phage therapy being extensively mobilized to meet the needs of the Soviet military beginning in 1939 with the Winter War with Finland, and later in World War II 9 .…”

The Safety and Efficacy of Phage Therapy for Bone and Joint Infections: A Systematic Review

“…Bacteriophages (phages) are viruses of bacteria whose discovery in 1915 and 1917 predates that of antibiotics [2]. The potential use of phages for the treatment of bacterial infections was quickly realised and throughout the early part of the 20th century phage therapy was 'en vogue' across Europe, the Americas and Russia [3][4][5]. However, the discovery of antibiotics catalysed the decline of phage therapy in the geopolitical West, where injudicious use, uncertainty about the nature of phages and manufacturing challenges conspired to dispel enthusiasm in phage therapy [6].…”

Tackling Multidrug Resistance in Streptococci – From Novel Biotherapeutic Strategies to Nanomedicines

“…Since their discovery in 1915 by Frederick William Twort, the phages were recognized as potential antibacterial, and due to the facility of administration and absence of side effects, phages were used immediately for antibacterial therapy (oral and topical preparations) ( Maciejewska et al, 2018 ). The discovery and introduction of penicillin in the 1940s led to the practically total abandonment of antibacterial therapy with phage in the western countries ( de Almeida and Sundberg, 2020 ). However, the benefits of antibiotics were lost considerably with the emergence and dissemination of bacterial resistance.…”

“…Since the 1980s, the phage therapy revival in western countries has been considered a possible option for combat antimicrobial resistance ( de Almeida and Sundberg, 2020 ). Many research groups have concentrated on this theme of increasing importance, with Belgium pioneering in studies for the clinical use of phages ( Pirnay et al, 2018 ; Jault et al, 2019 ).…”