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Secondary bacterial infection, especially with Streptococcus pneumoniae (Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naïve recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one.SignificanceAirborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection with Streptococcus pneumoniae reduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.

An earlier report on the effects of the sulfonamide drugs in tissues was published in collaboration with C. V. Weller in I942.' At that time few reports of this character had been released, but subsequently there has been an increasing number in the literature. As each new sulfonamide derivative was introduced, the hope that it would prove to be less toxic than preceding ones was revived; however, after it had been used for a time, investigation proved that comparable tissue changes took place in one or several organs of the body.The material utilized in this report includes 76 fatal cases investigated at the Army Institute of Pathology from I 93 7, when neoprontosil was first used therapeutically in Army hospitals, until I943, when a variety of sulfonamides were being employed.Skin taken for biopsy from 2 other cases was included in the material, making a total of 78 cases. This series is approximately onesixth of more than 500 cases in which one or another type of lesion had resulted from the administration of sulfonamides, but complicating disease factors caused the other cases to be eliminated. All cases were excluded in which sulfonamide drugs had been given in the treatment of any of the following conditions: septicemia, confirmed by blood culture; rheumatic fever; cardiovascular disease, including coronary thrombosis; poliomyelitis; scrub typhus or other proved viral or rickettsial infection; trichinosis; diphtheria; scarlet fever; typhoid fever; or miliary tuberculosis. However, in the presence of many of these complicating diseases, cellular infiltrates were observed which were identical with those regarded as the characteristic sulfonamide effect.The sulfonamide drugs which had been administered to the patients in this series included neoprontosil, sulfanilamide, sulfathiazole, sulfapyridine, sulfaguanidine, sulfadiazine, and the sodium salts of sulfathiazole, sulfapyridine, and sulfadiazine. Various combinations of these drugs were given to 24 patients. In four instances "sulfonamide therapy" was reported without reference to the specific drug employed (Table I).The total dosage of sulfonamide drugs received by the patients during the terminal illness varied from 8 to 340 gm., over periods ranging