The Pathogenesis of Bacterial Infections in Infants and Children: The Role of Viruses

THE PATHOGENESIS OF BACTERIAL INFECTIONS IN INFANTS AND CHILDREN: THE ROLE OF VIRUSES JON S. ABRAMSON* The majority of infants and children with bacterial infection do not have a known predisposing factor (e.g., trauma, immunodeficiency) leading to their illness. A recent international symposium, held at the University of Heidelberg, entitled "Perspectives on Bacterial Pathogenesis and Host Defenses" [1] explored possible mechanisms by which bacteria invade the host and overcome immune surveillance. The role that bacterial products (e.g., endotoxin, cytolysins) and host proteins (e.g., interleukins, tumor necrosis factor) play in the pathogenesis of bacterial disease was highlighted at this conference; however, the potential role of viruses in the pathogenesis of bacterial disease was not brought out. Considerable epidemiologic and experimental evidence exists that suggests that primary viral infections are a major predisposing event for both local and systemic bacterial infections. There is now compelling evidence that influenza virus, cytomegalovirus (CMV) and human immunodeficiency virus (HIV-I) lead to secondary bacterial infections in humans. There are also data, albeit less than for the above-mentioned viruses, that suggests that adenovirus, enterovirus, parainfluenza, respiratory syncytial virus (RSV), and rubeola virus are important in the pathogenesis of bacterial disease. Two related hypotheses will be discussed in this paper. The first is that viral infections are a major predisposing factor for bacterial infections in infants and children. The second hypothesis is that viruses predispose to bacterial infections through (1) a direct effect on mucosal tissues and (2) inhibition of various cells involved in local and systemic immune surveillance. Work supported in part by grant number AI-20506 from the National Institute of Allergy and Infectious Disease. Dr. Abramson is the recipient of a Research Career Development Award (AI-00670) from the National Institute of Allergy and Infectious Disease. The author thanks Drs. Larry Givner, Gary Wheeler, and Charles McCaIl for advice and criticism of the manuscript and Sandy Alexander for secretarial assistance. * Department of Pediatrics, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem, North Carolina 27103.© 1988 by The University of Chicago. All rights reserved. 003 1-5982/89/320 1-0603$0 1 .00 Perspectives in Biology and Mediane, 32, 1 · Autumn 1988 | 63 Evidence That Viral Infections Predispose the Host to Bacterial Disease Until recently, the best evidence that viral infections increase the risk of the host to secondary bacterial infections involved studies with influenza virus. Studies in animal models show that influenza virus can increase the incidence of secondary local and systemic diseases due to a variety of bacteria, which are common pathogens in children, including Streptococcus pneumoniae [2—5], Staphylococcus aureus [6, 7] and Haemophilus influenzae [8, 9].1 When influenza virus is inoculated into animals prior to or concomitant with these bacteria there is an increased incidence of bacterial pneumonia [2], otitis media [4, 5], sepsis, and meningitis [3, 4, 9] compared to in animals exposed to bacteria alone. Epidemiological studies done in humans with influenza virus infection indicate that the risk of otitis media, pneumonia, sepsis, and meningitis resulting from these same bacteria is increased [10-13]. More recently, studies involving other viruses have also supported the idea that viruses increase the susceptibility ofthe host to secondary infections . The CMV has been shown to increase the risk of superinfections in animals challenged with bacteria or fungi soon after their primary CMV infection [14, 15]. Human infants with CMV infection may also be at increased risk for secondary infections. Four immunocompetent infants with dual infections involving CMV and Pneumocystis carinii pneumonia , H. influenzae meningitis, and Escherichia coli meningitis have been reported [16]. Concomitant pulmonary infection with CMV and Chlamydia trachomatis, in infants, has also been documented [17]. Humans with HIV-I infection are at increased risk for bacterial pneumonia , gastroenteritis, urinary tract infections, deep and soft tissue abscesses and sepsis due mainly to S. pneumoniae, H. influenzae, S. aureus, and Salmonetta species [18, 19]. Secondary fungal and parasitic infections also play a major role in the morbidity and mortality associated with HIV-I infection. There is some evidence that other viruses can predispose the host to secondary infections with bacteria that are common pathogens in children . Adenovirus, parainfluenza virus, RSV, and rubeola virus have...