Reviews of infectious diseases最新文献

Coexistence of vertebral osteomyelitis and lesions of the aorta is rare but may be lethal if not diagnosed promptly and treated effectively. We describe a patient who was treated at the Cleveland Clinic Hospital, and we review 69 additional cases reported in the literature. The native aorta was involved in 66 cases; four patients developed infection of prosthetic aortic grafts. The most common aortic lesions associated with vertebral osteomyelitis were mycotic aneurysms, infected aneurysms, and pseudoaneurysms. The wide variety of pathogens involved included salmonellae and other gram-negative bacilli, mycobacteria, gram-positive cocci, and fungi. In some cases infection was polymicrobial. The condition was associated with protean clinical manifestations. Diagnosis was frequently delayed, and mortality was 71%. In some instances surgical procedures at sites of unsuspected aneurysms precipitated life-threatening hemorrhage. Therapy with antimicrobial drugs alone was insufficient. The best results were achieved when specific drug therapy was combined with resection of the infected aorta or aortic graft, thorough debridement, and extraanatomic bypass grafting.

Because of excellent and readily available animal models of infection with Strongyloides species, much of the basic biology of the parasite was understood by the early 1930s. Only selected issues of major physiologic importance were left to be addressed by intentional human infections. Concern about the strongyloides hyperinfection syndrome and the parasite's characteristic refractoriness to drug therapy led investigators of experimental human infections to act as subjects. This article reviews studies that describe experimental human infection with Strongyloides stercoralis and Strongyloides fülleborni as well as other Strongyloides species. These studies address two main issues: the clinical manifestations associated with the prepatent and early patent phases of infection, and the development of immunity to reinfection in individuals previously infected. The possible conclusions from these studies are discussed in the context of the current understanding of natural human and experimental animal infections.

This report describes the glycoproteins of varicella-zoster virus (VZV) and their role as immunogens and discusses the relevance of studies of VZV to the selection of a glycoprotein subunit herpes simplex virus (HSV) vaccine. HSV types 1 and 2 and VZV are alpha-herpesviruses, which are characterized by common biologic features such as a relatively short replication cycle and a latent state, often in neurologic tissues. The three viruses also conserve several glycoprotein genes, including gB, gC, gE, gH, and gI. The known properties of the VZV glycoproteins closely resemble those of their homologous HSV counterparts and may provide further insight into biologic functions of the immunogens. In particular, VZV glycoproteins gpII and gpIII closely resemble their HSV homologs gB and gH in that all four harbor complement-independent neutralization epitopes.

A herpes simplex virus subunit vaccine has been tested for immunogenicity and protective efficacy in animal models. The vaccine is a mixture of the viral glycoproteins gB and gD expressed in mammalian cells as secreted carboxyl terminal truncated derivatives. The antigens have been combined with several adjuvants, including a lipophilic derivative of a muramyl tripeptide, MTP-PE, and administered in a stable, low-oil emulsion. Titers of antibody that are threefold to 15-fold greater than those obtained with alum and within twofold of those generated with complete Freund's adjuvant are elicited in animals, including primates. Prophylactic immunization of guinea pigs provides nearly complete protection against intravaginal challenge with herpes simplex virus type 2. Treatment of previously infected guinea pigs reduces the frequency and severity of recurrent disease, although variations in efficacy dependent on the antigen, adjuvant, and dosing regimen employed are observed. The immunogenicity of this vaccine in animals provides the rationale for further testing in human clinical trials.

Current seroepidemiologic studies performed with assays that measure type-specific antibodies to herpes simplex virus (HSV) type 2 have demonstrated that infection due to the virus is common among women of child-bearing age. With regard to perinatal transmission of HSV, the virus infects nearly 50% of infants whose mothers have primary genital herpes, whereas less than 5% of infants exposed to recurrent maternal infection at the time of delivery become infected. Maternal immunity may also influence the clinical manifestations of neonatal herpes, with primary maternal infection more likely to be associated with disseminated disease in the infant. An effective HSV vaccine could alter the prevalence of neonatal herpes by (1) reducing women's risk of acquiring primary genital herpes during pregnancy and (2) boosting immunity in mothers for whom serologic evidence of previous infection due to HSV type 2 has been noted, which will enhance the transplacental transfer of virus-specific antibodies.

Experiences with the use of the live attenuated varicella vaccine for the immunization of varicella-susceptible adults and healthy and leukemic children are described. Healthy children, for whom a greater than 90% rate of seroconversion and protective efficacy was noted, showed the best response. Leukemic children experienced a 40%-50% rate of vaccine-associated rash; protective efficacy approached 90%. For adults, a 10% rate of vaccine-associated rash and a protective efficacy of 70% were noted. Breakthrough cases of vaccine were mild, indicating modification of the course of the illness by the vaccine.

Much of the evidence that implicates cytotoxic T lymphocytes (CTLs) in the control of infections due to herpes simplex virus (HSV) is circumstantial. However, the ease of induction of HSV-specific CTLs in vitro, the evidence from clinical observations in humans, and the protection afforded by adoptively transferred CTLs all tend to support an important role for CTLs in the resolution of HSV disease. One salient feature of the response of human CTLs to HSV that has emerged quite clearly is the presence of CD4+ T cells as a predominant killer cell phenotype. Given the importance of CD4+ T cells in mediating delayed type hypersensitivity responses and in clearing local infections on adoptive transfer, this T cell subset probably plays a critical role in the resolution of HSV recrudescent disease. Moreover, it is tempting to speculate that viral agents that impair the function of CD4+ T cells, such as human immunodeficiency virus type 1, may predispose patients to severe local infections.