Modern management of cutaneous bacterial infections.
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Skin infection occurs in any age-group, sex, and race but is particularly common in children. It is usually minor, but may indicate underlying systemic disease or may lead to systemic infection. Streptococci and staphylococci are common causes. Group A beta-hemolytic streptococci account for the majority of streptococcal infections in man. Infection most often involves the lower extremities and produces spreading erythema and necrosis but little purulence. Staphylococcal infections most commonly involve the face, the hair follicles and eccrine sweat ducts being the initial sites. Lesions appear as bullae and pustules with a narrow rim of erythema. Intense cellulitis surrounding the lesions usually points to a virulent, penicillin-resistant strain of Staphylococcus. Treatment of both types of infection consists of cleansing with antibacterial agents, removal of crusts, application of warm compresses, and use of topical or systemic antibiotics, depending on the severity of the infection and the type of pyoderma involved.
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We report two cases of orf, a common viral disease of sheep, which occurred in residents of Missouri. A survey taken among sheep raisers in Missouri revealed that many were unaware of this as a potential human disease. It is important for physicians to be able to recognize this lesion so that radical methods of therapy are not employed. The lesion heals without scarring and without specific therapy. Complications are rare.
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PURPOSE OF REVIEW: A summary of recent advances in our knowledge of the biology of orf virus is presented to illustrate the interaction of a zoonotic pathogen with host skin. This is providing novel and interesting data on the viral mechanism of skin infection and the host response. RECENT FINDINGS: The full genome sequences of two parapoxviruses (orf virus and bovine papular stomatitis virus) have recently been published, defining the parapoxvirus genus at the molecular genetic level. This, along with more detailed characterization of viral immuno-modulatory proteins, is providing an insight into the acquisition of host genes and the mechanism of pathogenesis. A new chemokine-binding protein has been discovered with unique features. Structure-function analysis of the viral granulocyte/macrophage colony-stimulating factor inhibitory factor has revealed a similarity to type 1 cytokine receptors. The viral vascular endothelial growth factor-E stimulates angiogenesis in the skin without the side effects seen with cellular vascular endothelial growth factor-A, and may have therapeutic potential. Finally, orf virus is proving useful both as an immuno-modulator and as a vector for the expression of foreign antigens in non-permissive species. SUMMARY: Orf virus infection provokes a vigorous skin immune response. However, the virus has acquired a range of immuno-modulatory/pathogenesis-related genes that function to limit (at least transiently) the effectiveness of host immunity. With the advent of the orf virus genome sequence, the study of this dynamic process will provide important insights into virus pathogenesis and the host skin immune response to infection.
During ultrahistological investigations of naturally occurring cases of stomatitis papulosa in cattle and Orf in sheep, nuclear changes consisting of aggregations of double membrane-containing tubular structures (outer diam. 100 to 130 nm, inner diam. 50 to 65 nm) and filamentous material were observed. These changes could be reproduced in vitro after infection of bovine (BEL) and ovine (OEL) embryonic lung cell cultures with stomatitis papulosa virus and Orf virus isolates. Nuclear tubules were mostly associated with stomatitis papulosa, whereas filaments were regularly detected in Orf virus infections in vivo. Stomatitis papulosa virus also induced nuclear tubules in vitro in the two cell culture types employed, whereas tubular structures after Orf virus infection only developed in ovine embryonic lung cell cultures in addition to filamentous structures. Orf virus infection of BEL cell cultures induced the formation of filaments. Fluorescent antibody staining revealed parapoxvirus-specific antigens only in the cytoplasm of infected cells.
Restriction endonuclease analysis of the DNA extracted orf virus strain NZ2, which had been serially passaged in primary bovine testis cells, revealed a population of variants that had over-grown the wild-type virus. At least three distinct mutant forms were identified in which the right end of the genome had been duplicated and translocated to the left end, accompanied by deletions of sequences at the left end. Sequencing of a single variant isolated from the heterogeneous population revealed that recombination had occurred between non-homologous sequences. In this case, 6.6 kb of DNA at the left end of the genome had been replaced by 19.3 kb from the right end. The transposition resulted in the deletion at the left end of 3.3 kb of DNA encoding three genes and the terminal sequences of a fourth gene. The three genes completely deleted were a homologue of dUTPase, a gene that encodes a protein containing ankyrin-like repeats and a homologue of the 5K gene of the vaccinia virus WR strain. Experimental inoculation of sheep showed that the genes are also non-essential in vivo, but that the size of the lesion was reduced, compared with that induced by the wild-type, and resolved more rapidly.
Following orf virus reinfection in sheep, CD8+ T cells were recruited to the lesion site in the skin during the period of viral replication and appeared in increased numbers in afferent lymph draining the infection site. A proportion of the CD8+ T cells were activated, particularly in the skin, as determined by their expression of the cytolytic cell-associated serine protease, BLT-esterase. This was a useful marker for activated cytolytic cells as there was a good correlation between afferent lymph CD8+ T cell-mediated lysis of autologous orf virus-infected skin cells and their expression of BLT-esterase in vitro. The majority of the cells that expressed BLT-esterase in the skin and lymph were CD8+ T cells and cytolysis in vitro was predominately by the MHC class I antigen presentation pathway. The conclusion is that orf virus reinfection is characterized by limited viral replication and stimulation of an activated CTL response in the skin.
Vibrio cholerae is the aetiological agent of the deadly diarrhoeal disease cholera. In this study the 7.5 kb Vibrio seventh pandemic island-II (VSP-II) that is unique to V. cholerae El Tor and O139 serogroups was analysed and it was found to be part of a novel 26.9 kb genomic island (GEI) encompassing VC0490-VC0516. The low-GC-content VSP-II encompassed 24 predicted ORFs, including DNA repair and methyl-accepting chemotaxis proteins, a group of hypothetical proteins and a bacteriophage-like integrase adjacent to a tRNA gene. Interestingly, V. cholerae ORFs VC0493-VC0498, VC0504-VC0510 and VC0516, which encodes an integrase, were homologous to Vibrio vulnificus strain YJ016 ORFs VV0510-VV0516, VV0518-VV0525 and VV0560, which also encodes an integrase, respectively. Some ORFs showed amino acid identities greater than 90 % between the two species in these regions. In V. vulnificus strain YJ016, a 43.4 kb low-GC-content (43 %) GEI encompassing ORFs VV0509-VV0560 was identified and named V. vulnificus island-I (VVI-I). The 52 ORFs of VVI-I included a phosphotransferase system gene cluster, genes required for sugar metabolism and transposase genes. There was synteny and homology between the 5' region of V. cholerae VSP-II and the 5' region of V. vulnificus VVI-I; however, VVI-I contained an additional 31.5 kb of DNA between VV0526 and VV0560 in strain YJ016. A second V. vulnificus strain, CMCP6, did not contain the 43.4 kb VVI-I; in this strain two ORFs were found between the 5' and 3' flanking genes VV10636 and VV10632, showing 100 % identity to VV0508 and VV0561, respectively, which flank VVI-I.
Most of the major advances in modern virology during the past 25 years have been due principally to the development of refined laboratory techniques and tools and have provided a fund of new knowledge and information about the nature of viral infection and pathogenesis. One group of viruses of interest to dermatologists, the herpesviruses, is undergoing intensive biochemical investigation to determine whether it is carcinogenic. As a result of the success of the World Health Organization's campaign to eradicate smallpox, it is predicted that by the end of 1976, smallpox will have been eradicated. Other viruses of dermatologic interest which are now being studied include the agents of warts, molluscum contagiosum, cat-scratch disease, and enteroviruses. Current research in the field of viral chemotherapy may provide the basis for successfully treating these diseases in the future.