Rapidly Fatal Hemorrhagic Pneumonia and Group AStreptococcus Serotype M1

Maria Santagati1, Teresa Spanu1, Marina Scillato, Rosaria Santangelo, Fabio Cavallaro, Vincenzo Arena, Giacomo Castiglione, Marco Falcone, Mario Venditti, and Stefania Stefani

Author affiliations: University of Catania, Catania, Italy (M. Santagati, M. Scillato, S. Stefani); Catholic University of the Sacred Heart, Rome, Italy (T. Spanu, R. Santangelo, F. Cavallaro, V. Arena); Vittorio Emanuele Hospital, Catania (G. Castiglione);University of Rome La Sapienza, Rome (M. Falcone, M. Venditti)

Abstract

We report 3 cases of fulminant hemorrhagic pneumonia in previously health patients. Sudden-onset hemoptysis and dyspnea developed; all 3 patients and died < 12 h later of massive pulmonary bleeding, despite aggressive supportive care. Postmortem analysis showed that the illnesses were caused by group A Streptococcus emm1/sequence type 28 strains.

Streptococcus pyogenes or group A Streptococcus (GAS) is a versatile pathogen that can cause serious diseases, including bacteremia, cellulitis, puerperal sepsis, meningitis, pneumonia, and necrotizing fasciitis (1,2). This pathogen also causes streptococcal toxic shock syndrome, a severe response to streptococcal pyrogenic exotoxins (Spe proteins), which trigger overproduction of inflammatory cytokines, leading to tissue damage, organ failure, and shock (3,4). Despite improved awareness and treatment, GAS infections remain among the top 10 infectious causes of fatal disease in humans (1).

Periodic resurgences of invasive GAS infections in industrialized countries have been linked to emergence of dominant GAS clones resulting from horizontal gene transfer (5–8). The ability of these clones to cause life-threatening disease in healthy persons probably depends on expression of virulence factors that facilitate penetration of host cell barriers and evasion of immune defenses (3,4,8).

More than 250 GAS types have been identified in sequencing studies of the hypervariable region of the emm gene, which encodes the M surface protein (1,2). The emm types seem to correlate with tissue tropism of the organism, and M protein augments GAS virulence by interfering with antibody and complement deposition, facilitating formation of microcolonies and neutralizing antimicrobial peptides, and stimulating proinflammatory and procoagulatory activities (3,4). M1 protein and M1 fragments released by neutrophil proteases can also provoke pulmonary hemorrhage, inflammation, and tissue destruction by their interaction with fibrinogen, which causes neutrophils to release heparin-binding protein, a mediator of vascular leakage (9). The hypervirulent emm1 GAS clone also harbors prophages encoding SpeA proteins and extracellular streptodornase D (Sda1), which can also enhance virulence and dissemination (8,10). We report 3 cases of rapidly fatal, hemorrhagic pneumonia in previously healthy patients that were determined to be caused by infection with hypervirulent GAS.