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PubMed1996

Detection and preliminary characterization of a new rabbit calicivirus related to rabbit hemorrhagic disease virus but nonpathogenic.

A new rabbit calicivirus related to the rabbit hemorrhagic disease virus (RHDV) was identified. The new virus contains significant differences from the previously characterized RHDV isolates in terms of pathogenicity, viral titer, tropism, and primary sequence of the structural protein. Cross-protection experiments, antigenic data, and sequence comparisons demonstrate that the new virus is more closely related to RHDV than to the European brown hare syndrome virus, another member of the caliciviruses of the lagomorph group. The existence of a nonpathogenic calicivirus, which we propose to name rabbit calicivirus (RCV), provides an explanation for the early discrepancies found in the course of serological surveys of the rabbit population in European countries.

Amino Acid Sequence↗

PubMed2000

Sequences of Citrus tristeza virus separated in time and space are essentially identical.

The first Citrus tristeza virus (CTV) genomes completely sequenced (19.3-kb positive-sense RNA), from four biologically distinct isolates, are unexpectedly divergent in nucleotide sequence (up to 60% divergence). Understanding of whether these large sequence differences resulted from recent evolution is important for the design of disease management strategies, particularly the use of genetically engineered mild (essentially symptomless)-strain cross protection and RNA-mediated transgenic resistance. The complete sequence of a mild isolate (T30) which has been endemic in Florida for about a century was found to be nearly identical to the genomic sequence of a mild isolate (T385) from Spain. Moreover, samples of sequences of other isolates from distinct geographic locations, maintained in different citrus hosts and also separated in time (B252 from Taiwan, B272 from Colombia, and B354 from California), were nearly identical to the T30 sequence. The sequence differences between these isolates were within or near the range of variability of the T30 population. A possible explanation for these results is that the parents of isolates T30, T385, B252, B272, and B354 have a common origin, probably Asia, and have changed little since they were dispersed throughout the world by the movement of citrus. Considering that the nucleotide divergence among the other known CTV genomes is much greater than those expected for strains of the same virus, the remarkable similarity of these five isolates indicates a high degree of evolutionary stasis in some CTV populations.

Base Sequence↗

PubMed1999

Equine influenza in the United Kingdom in 1998.

In 1998, equine influenza was diagnosed by serology and nucleoprotein enzyme-linked immunosorbent assay as the cause of acute respiratory disease in vaccinated and unvaccinated horses in the UK. The signs were generally milder in vaccinated horses and completely susceptible animals showed the most severe signs, including pyrexia, inappetence, coughing, mucopurulent nasal discharge and secondary bacterial pneumonia. In a detailed investigation of an outbreak among 52 vaccinated thoroughbreds in a flat racing yard, more than 60 per cent of the horses seroconverted on the evidence of paired serum samples tested by single radial haemolysis (SRH). Preliminary sequencing and characterisation of an isolate from this outbreak indicated that it was an 'American-like' strain. In addition, in this outbreak there was a larger proportion of horses with preinfection SRH titres greater than 140 mm2 that subsequently seroconverted than in other recent outbreaks from which 'European-like' strains have been isolated. This result suggested that the cross-protectivity between circulating 'American-like' strains and the 'European-like' strains of A/equine-2 viruses present in current vaccines may be decreasing.

Animals↗

PubMed1995

How Salmonella survive against the odds.

The enteric pathogen Salmonella typhimurium faces daunting odds during its voyages in the natural environment and through an infected host. It must manage stresses ranging from feast to famine, acid to base, and high to low osmolarity, among others, as well as counter various types of oxidative stress and a variety of antimicrobial peptides. The defenses used to survive these encounters can be specific or can provide cross protection to a variety of hostile conditions. Once inside a host, Salmonella spp. escape the extracellular environment and thus humoral immunity by invading professional and nonprofessional phagocytes in which a new set of challenges await. Some of these stresses are similar to those encountered in the natural environment (e.g. acid, starvation) but the bacterial response is complicated by the simultaneous occurrence of multiple stresses. S. typhimurium appears to sense various in vivo cues and responds by seducing the host signal-transduction pathways that are required to phagocytize the bacterial cell. The pathogen then calls upon components of its stress-response arsenal to survive the intracellular environment. These survival strategies enable the organism to persist in nature, where conditions are usually suboptimal, and equip the bacterium with pathogenic properties that, if successful, will provide it with a very rich and stress-free growth environment, a dead host.

Adaptation, Physiological↗

PubMed1998

Control of papaya ringspot virus in papaya: a case study.

The papaya crop is severely affected by papaya ringspot virus (PSRV) worldwide. This review focuses on efforts to control the destructiveness of the disease caused by PSRV in Hawaii, starting from the use of cross protection to parasite-derived resistance with transgenic papaya expressing the PSRV coat protein gene. A chronology of the research effort is given and related to the development of technologies and the pressing need to control PSRV in Hawaii. The development of commercial virus-resistant transgenic papaya provides a tangible approach to control PSRV in Hawaii. Moreover, the development of transgenic papaya by other laboratories and employment of a mechanism of effective technology transfer to different countries hold promise for control of PSRV worldwide.

Journal Article↗

PubMed2002

Tobacco mosaic virus assembly and disassembly: determinants in pathogenicity and resistance.

The structural proteins of plant viruses have evolved to self-associate into complex macromolecules that are centrally involved in virus biology. In this review, the structural and biophysical properties of the Tobacco mosaic virus (TMV) coat protein (CP) are addressed in relation to its role in host resistance and disease development. TMV CP affects the display of several specific virus and host responses, including cross-protection, systemic virus movement, hypersensitive disease resistance, and symptom development. Studies indicate that the three-dimensional structure of CP is critical to the control of these responses, either directly through specific structural motifs or indirectly via alterations in CP assembly. Thus, both the structure and assembly of the TMV CP function as determinants in the induction of disease and resistance responses.

Biological Transport↗

PubMed1994

Superresistance against hypoxia after preliminary adaptation to repeated stress.

The study investigated the influence of adaptation to stress on resistance to hypoxia. After rats were adaptated to moderate restraint stress, they were anesthetized and exposed to 6% O2. Adaptation increased tidal volume by 2.6-fold, lung and alveolar ventilation by 1.6- and 1.8-fold, respectively, and O2 consumption by 1.6-fold; limited lactate accumulation in the liver by 2-fold, in the heart by 34%, in the lung by 36%, and in the blood by 36%; and elevated pH. At the same time, preliminary adaptation to stress inhibited the hypoxic activation of lipolysis and peroxidation in all tissues. The concentration of lipid peroxides decreased after adaptation by 1.3- to 1.5-fold in different organs, whereas the content of free fatty acids diminished by 1.7- to 2.3-fold. Finally, after adaptation, mortality decreased under severe hypoxia by 6.5-fold. Thus, the data suggest that the cross-protective effect of adaptation was achieved by the economization of respiration and circulation, by marked augmentation in the ability of tissue to utilize blood O2, and by the limitation of processes that are able to damage tissue membranes, namely, acidosis, lipolysis, and lipid peroxidation.

Acid-Base Equilibrium↗

PubMed1999

Hepatitis E virus. Advances in HEV biology and HEV vaccine approaches.

Hepatitis E, previously known as enterically transmitted, enteric, or epidemic hepatitis, is a worldwide public health problem. The causative agent, the hepatitis E virus, is involved in epidemic, sporadic, and fulminant hepatitis cases worldwide. This review describes the advances in the biology of the hepatitis E virus and the progress made to develop simple and robust serologic assays for the diagnosis of HEV infection. Genomic sequence comparisons with a recently identified US isolate now suggests three genetic groups of HEV viruses. A highly conserved animal isolate found in pigs suggest the coexistence of animal and human isolates of HEV. The use of recombinant technology to develop an effective subunit vaccine capable of providing cross-protection for the most divergent HEV strains has been established and is reviewed.

Animals↗

PubMed1991

Taxonomy of potyviruses: current problems and some solutions.

There are two major requirements for potyvirus taxonomy; group-specific criteria and criteria which discriminate between distinct viruses and strains. This review discusses the relative merits in potyvirus taxonomy of molecular parameters, such as gene sequence data, nucleic acid hybridization, coat protein sequence data, or high-performance liquid chromatography peptide profiles, and phenotypic characteristics, such as particle morphology, host range, symptomatology, cross-protection, cytoplasmic inclusion morphology, and serology. Coat protein and gene sequence data are the most useful criteria, as they can be used to distinguish viruses from strains and to establish evolutionary relationships between groups of distinct potyviruses. This has led to the revised classification of some viruses and strains and to the clarification of previously conflicting and inconsistent biological properties. It has also provided a sound basis for subgrouping potyviruses. An analysis of the data supports the view that the potyvirus group, including the non-aphid-transmitted viruses, should be elevated to family status, that the vector transmission mode, which correlates with major sequence diversity, should define the four genera, and that distinct potyviruses correspond to species and their variants to strains.

Amino Acid Sequence↗

PubMed1985

Effects of pneumococcal vaccination on tonsillo-pharyngitis and upper respiratory tract flora.

The effect of a 14-valent pneumococcal vaccine on upper respiratory tract infections and carriage of beta-haemolytic streptococci was studied in a double-blind prospective study of 405 children 0.5-5 years of age. In the children under 2 years of age at vaccination, the cases of acute tonsillitis were more frequent among the vaccinees than among the controls (p less than 0.01). In contrast, among the children over 2 years of age at vaccination, fewer episodes of acute tonsillitis were reported among the vaccinees than among the controls (p less than 0.01). In the older age group, the total rate of upper respiratory tract infections was also significantly reduced. Similarly, an increase in asymptomatic carriage of group A streptococci was registered in children vaccinated at 2-5 years of age (p less than 0.01). Inversely, the carriership of group C streptococci diminished among the vaccinated children (p less than 0.05). Some possible mechanisms underlying these unexpected findings, including non-specific mitogenic features and cross-protection due to antigenic similarities, were explored.

Age Factors↗

PubMed2006

Strategies to enhance price and quality competition in health care: lessons learned from tracking local markets.

Drawing on observations from tracking changes in local health care markets over the past ten years, this article critiques two Federal Trade Commission and Department of Justice recommendations to enhance price and quality competition. First, we take issue with the notion that consumers, acting independently, will drive greater competition in health care markets. Rather we suggest an important role remains for trusted agents who can analyze inherently complex price and quality information and negotiate on consumers' behalf. With aggregated information identifying providers who deliver cost-effective care, consumers would be better positioned to respond to financial incentives about where to seek care and thereby drive more meaningful competition among providers to reduce costs and improve quality. Second, we take issue with the FTC/DOJ recommendation to provide more direct subsidies to prevent distortions in competition. In the current political environment, it is not practical to provide direct subsidies for all of the unfunded care that exists in health care markets today; instead, some interference with competition may be necessary to protect cross subsidies. Barriers can be reduced, though, by revising pricing policies that have resulted in marked disparities in the relative profitability of different services.

Catchment Area, Health↗

PubMed2006

A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology.

BACKGROUND: The burden of shigellosis is greatest in resource-poor countries. Although this diarrheal disease has been thought to cause considerable morbidity and mortality in excess of 1,000,000 deaths globally per year, little recent data are available to guide intervention strategies in Asia. We conducted a prospective, population-based study in six Asian countries to gain a better understanding of the current disease burden, clinical manifestations, and microbiology of shigellosis in Asia. METHODS AND FINDINGS: Over 600,000 persons of all ages residing in Bangladesh, China, Pakistan, Indonesia, Vietnam, and Thailand were included in the surveillance. Shigella was isolated from 2,927 (5%) of 56,958 diarrhoea episodes detected between 2000 and 2004. The overall incidence of treated shigellosis was 2.1 episodes per 1,000 residents per year in all ages and 13.2/1,000/y in children under 60 months old. Shigellosis incidence increased after age 40 years. S. flexneri was the most frequently isolated Shigella species (1,976/2,927 [68%]) in all sites except in Thailand, where S. sonnei was most frequently detected (124/146 [85%]). S. flexneri serotypes were highly heterogeneous in their distribution from site to site, and even from year to year. PCR detected ipaH, the gene encoding invasion plasmid antigen H in 33% of a sample of culture-negative stool specimens. The majority of S. flexneri isolates in each site were resistant to amoxicillin and cotrimoxazole. Ciprofloxacin-resistant S. flexneri isolates were identified in China (18/305 [6%]), Pakistan (8/242 [3%]), and Vietnam (5/282 [2%]). CONCLUSIONS: Shigella appears to be more ubiquitous in Asian impoverished populations than previously thought, and antibiotic-resistant strains of different species and serotypes have emerged. Focusing on prevention of shigellosis could exert an immediate benefit first by substantially reducing the overall diarrhoea burden in the region and second by preventing the spread of panresistant Shigella strains. The heterogeneous distribution of Shigella species and serotypes suggest that multivalent or cross-protective Shigella vaccines will be needed to prevent shigellosis in Asia.

Adolescent↗

PubMed2001

Vaccines against meningococcal disease: current and future technologies.

Development of the meningococcal serogroup C conjugate vaccine and its national implementation in the UK has been a major breakthrough in the prevention of meningococcal disease. New technologies are increasing the likelihood that research towards a vaccine against group B meningococcus will be successful. This review covers the recent development of vaccines against meningococcal disease and examines future vaccine candidates. The development of meningococcal polysaccharide vaccines was based on the virulence of the bacterial capsule components. The immunogenicity of these vaccines has been improved by covalent linkage to proteins in the new meningococcal C conjugate vaccines. However, the most promising developments for serogroup B disease have stemmed from other virulence determinants such as outer membrane proteins (OMPs) and lipopolysaccharides (LPS). New genome sequencing technology promises a way forward to developing a broadly cross-protective vaccine for this important pathogen.

Adolescent↗

PubMed2005

Emerging human papillomavirus vaccines.

Human papillomavirus (HPV) infections are a leading cause of virus-associated cancers of the anogenital, oropharyneal and cutaneous epithelium. The most prevalent of these is cervical cancer, which is responsible for approximately 500,000 deaths annually worldwide. A group of about 15 serologically unrelated 'high-risk' HPV types are responsible for almost all HPV-associated cancers. Prevention of papillomavirus infection can be achieved by induction of capsid-specific neutralising antibodies in preclinical animal papillomavirus models and in recent human clinical trials. High titres of conformationally-dependent, type-specific HPV-neutralising antibodies are triggered by HPV virus-like particle (VLP) vaccines. Overcoming the problems of type-specificity of the responses to these VLP vaccines is a potentially important area of current HPV vaccine research, with an emphasis on induction of more broadly cross-protective neutralising responses. Viral oncogenes E6 and E7 are continuously present in HPV-associated cancers and are prime targets for HPV therapeutic vaccines. A variety of approaches are being tested in therapeutic vaccine clinical trials and in various preclinical animal papillomavirus models for efficacy. Approaches include genetic vaccines, recombinant virus vaccines, dendritic cell-based strategies, immunomodulatory strategies and various combination strategies to maximise cell-mediated immunity to papillomavirus proteins present in HPV infections and cancers. The success of preventive HPV VLP vaccines in clinical trials is clear. However, current therapeutic vaccine trials are less effective with respect to disease clearance. Nevertheless, a series of combination approaches have shown significant therapeutic enhancement in preclinical papillomavirus models and await testing in patient populations to determine the most effective strategy. There is much encouragement that HPV vaccines will be the most effective approach to prevention and cure of infections caused by this group of viruses, which re-present a significant human pathogen.

Clinical Trials as Topic↗

PubMed2001

Serotype prevalence of occult pneumococcal bacteremia.

OBJECTIVE: The licensure and use of a pneumococcal conjugate vaccine that is immunogenic in children who are younger than 2 years may affect the epidemiology of occult bacteremia. This study was conducted to determine the serotype prevalence of Streptococcus pneumoniae isolates from children with occult bacteremia and to document the proportion that would be covered by the recently licensed heptavalent pneumococcal conjugate vaccine. METHODS: A cohort of 5901 children who were 2 to 24 months of age and had a temperature of >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department was studied to determine the prevalence of S pneumoniae serotypes. Patients were excluded if their immune system was suppressed, they had a diagnosis of a focal infection, they were evaluated by lumbar puncture, they were admitted to the hospital, or they died during initial evaluation. Blood cultures were inoculated into pediatric blood culture bottles and processed using an automated carbon dioxide monitoring system. All pneumococcal isolates were serotyped on the basis of capsular swelling with type-specific antisera (Quellung reaction). RESULTS: The study population consisted of 5901 patients. The overall rate of occult bacteremia was 1.9% (95% confidence interval [CI]: 1.5-2.3). S pneumoniae accounted for 92 of 111 isolates (82.9%; 95% CI: 74.6-89.4) in children with occult bacteremia. Eight pneumococcal serotypes were represented: 6A (2%), 9V (6%), 19F (6%), 18C (8%), 4 (9%), 6B (13%), 23F (15%), and 14 (42%). Serotypes 14, 6B, and 23F accounted for 69.3% (95% CI: 58.6-78.7) of typed isolates. In the cohort, 97.7% (95% CI: 92-99.7) of isolated serotypes are represented in the newly licensed heptavalent pneumococcal conjugate vaccine. The single isolated serotype that would not have been covered by the currently licensed heptavalent pneumococcal conjugate vaccine was 6A. CONCLUSIONS: S pneumoniae accounts for the vast majority of bacterial pathogens in children with occult bacteremia. As indicated by the results of this study, the heptavalent pneumococcal conjugate vaccine may prevent the majority of occult pneumococcal bacteremia episodes. The 2 cases of bacteremia with a serotype that would not have been included in the vaccine both were due to serotype 6A. It has been noted that there is potential nonvaccine serotype and subgroup cross-protection (6A from 6B) afforded to children who are immunized with the heptavalent vaccine. The high potential efficacy of the heptavalent pneumococcal conjugate vaccine for strains that cause occult bacteremia in our population may have a profound effect on the treatment of children with fever without a source. There has been an alarming and rapid emergence of antibiotic-resistant pneumococcal strains. Less pressure to use broad-spectrum antibiotics, which in turn causes further antibiotic resistance, should result. Laboratory testing and hospitalization also should be reduced. The prevalence rates determined by this study may be used as baseline data for comparison of serotype rates of occult pneumococcal bacteremia after widespread use of the heptavalent vaccine.

Bacteremia↗

PubMed2002

Vaccines against hantaviruses.

Rodent-borne hantaviruses are etiologic agents for hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome in the Old World and New World, respectively. These often severe diseases are relatively uncommon in most parts of the world and are sufficiently genetically variable that widely cross-protective vaccines will probably need to be polyvalent. The current status of hantavirus vaccines shall be reviewed and both conventional and speculative new vaccine technologies that may evolve within the field shall be considered.

Animals↗

PubMed2003

Conjugate vaccines.

Conjugate vaccines in which the capsular polysaccharide of Haemophilus influenzae type b, common serotypes of Streptococcus pneumoniae and group C Neisseria meningitidis are covalently bound to a protein antigen to convert a T-cell-independent immune response into a T-cell-dependent response have proved highly effective in the prevention of invasive disease in infants and young children. This review looks at what has been learnt from developing these vaccines that could be useful for the clinical development of future conjugate vaccines, in such areas as combination vaccines, dose-ranging, cross-protection of closely related antigens, prevention of noninvasive disease, correlates of protection and use in older age groups. In addition, a wide range of other organisms may be susceptible to conjugate vaccines and new indications and approaches are considered. This will be a highly active area for many years to come.

Child↗

PubMedDate not supplied

Trypanosoma rangeli (Tejera, 1920) isolated from a sylvatic rodent (Echimys dasythrix) in Santa Catarina Island, Santa Catarina State: first report of this trypanosome in southern Brazil.

A trypanosome strain isolated from a sylvatic rodent (Echimys dasythrix) from Santa Catarina Island (Santa Catarina State, Brazil) was characterized by the following methods: experimental transmission and development in invertebrate and vertebrate hosts, morphometry, cross protection, complement sensitivity, lectin agglutination and isoenzyme profiles. Comparisons were made with standard Trypanosoma cruzi and T. rangeli strains. All methods except isoenzyme analysis led to the identification of the isolate as T. rangeli. The isoenzyme differences found could be explained on the basis of polymorphism. Therefore this is the first report of T. rangeli in southern Brazil, increasing the geographical distribution of this parasite.

Animals↗