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Detection and response to a meningococcal disease outbreak following a youth football tournament with teams from four European countries.

An outbreak of meningococcal disease, caused by Neisseria meningitidis, occurred following an international youth football tournament in the summer of 1997, affecting individuals from four European countries. This paper describes the outbreak, focusing on international co-operation in detection, investigation, control and follow-up, identifying weaknesses and exploring opportunities for improved co-operation. Data came from interviews, reports and related documents. The detection and management of the outbreak in each country is analysed. Eleven cases were linked to this outbreak and serotyped as C:2a:P1.5. Control measures varied in each country, reflecting different national guidelines. The outbreak illustrated deficiencies in management of international outbreaks but also demonstrated benefits of international co-operation.

Adolescent↗

Triacylglycerol metabolism is a novel target to combat West Nile virus infection.

West Nile virus (WNV) is a zoonotic Orthoflavivirus transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.

West Nile virus; lipid↗

Elimination of indigenous measles from the United States.

In October 1978, a nationwide initiative to eliminate indigenous measles from the United States by October 1, 1982, was announced. The measles elimination program has three major elements: attaining and maintaining high immunization levels, aggressive and effective surveillance, and vigorous response to cases. In 1980, immunization levels in children entering school for the first time were 96%, indicating that the necessary levels have been attained in the age group. Mechanisms are in place to assure maintenance of these levels; these rely heavily on the use of immunization requirements for school attendance in each state. Aggressive surveillance systems have been developed for each state to detect suspected measles cases as soon as possible after they occur and to investigate them within 24 hr of notification. The clinical definition of measles used is fever of greater than or equal to 101 F (38.3 C); rash of three or more days duration; and cough, coryza, or conjunctivitis. The response to outbreaks involves identifying persons in the area who are at risk of contracting measles, determining those who are possibly susceptible, and ensuring that these persons are vaccinated. In school outbreaks, susceptible students are vaccinated or excluded from school until the outbreak is over. During 1981, measles morbidity reached a record low level of only 3,032 reported cases (provisional total). Epidemic measles occurred in only a few outbreaks of limited size and duration, and endemic cases were restricted to a small number. Imported cases averaged slightly more than two per week, occasionally producing limited outbreaks, but more often resulting in no secondary spread. Transmission of measles has been interrupted in most of the United States. With continued vigorous implementation of the current strategy and with additional measures to lessen the risk of importations, it appears likely that the goal to eliminate indigenous measles transmission will be attained by October 1982.

Adolescent↗

Analysis of increasing antibiotic resistance of Klebsiella pneumoniae relative to changes in chemotherapy.

Three antibiotic-resistant strains of Klebsiella pneumoniae responsible for outbreaks of systemic infection in a hospital nursery were analyzed. Each organism emerged after prolonged use of a drug to which it was resistant. The first strain (RO16) produced neomycin phosphotransferase and contained three plasmids with molecular weights of 24, 25, and 30 X 10(6) daltons, respectively. Resistance to ampicillin, carbenicillin, neomycin, and kanamycin was transferred by conjugation at a frequency of 10(-6). The second strain of K. pneumoniae (RO106) produced gentamicin adenyltransferase and maintained aminoglycoside resistance only when propagated in antibiotic-containing medium. DNA analyses revealed eight species of plasmid DNA: one species with a molecular weight of 70 X 10(6) daltons apparently accounted for conjugal transfer of resistance to ampicillin, carbenicillin, chloramphenicol, and streptomycin. The third strain (RO180) was resistant primarily to colistin and lacked plasmids. Control of the outbreak due to this strain was achieved by aminoglycoside therapy.

Aminoglycosides↗

Non-O group 1 Vibrio cholerae: a look at the epidemiology of an occasional pathogen.

Non-O1 V. cholerae is a ubiquitous environmental isolate. It is a common contaminant of shellfish, and in the developing world, it is frequently isolated from food and water. Asymptomatic carriage rates approaching 4 percent have been described among persons involved in high-risk activities, such as eating oysters in New Orleans or going on pilgrimage to Mecca. The actual occurrence of disease appears to be much less common. This is an "occupational" pathogen which may be responsible for outbreaks or a high frequency of isolation in certain areas at specific times but which generally ranks as a minor cause of diarrheal disease. While host susceptibility and infectious dose may help explain the relatively infrequent occurrence of non-O1 V. cholerae-associated disease, it also appears likely that only a small minority of strains carry the necessary virulence factors to cause gastroenteritis. Unfortunately, there does not appear to be a single mechanism by which these organisms cause diarrhea; it is likely that we will find a heterogeneous pattern of virulence mechanisms, similar to the heterogeneity seen among diarrheagenic E. coli. As our understanding of these pathogenic mechanisms improves, there should be a corresponding refinement in our understanding of the epidemiology of these widely distributed organisms.

Adult↗

Microbe Profile: Salmonella Typhimurium: the master of the art of adaptation.

Salmonella Typhimurium is a major Salmonella serovar that is found globally. It is responsible for outbreaks of self-limiting gastroenteritis that are broadly linked to the industrialization of food production. S. Typhimurium is a pathogen with a broad host range and remarkable metabolic versatility. The ∼5 Mb genome includes the pSLT virulence plasmid and has a characteristic prophage repertoire. The major virulence determinants are encoded by a variety of pathogenicity islands. Emerging multidrug-resistant lineages of epidemics of S. Typhimurium are currently causing bloodstream infections in sub-Saharan Africa. The versatility and adaptability of S. Typhimurium pose an important public health challenge.

Salmonella typhimurium↗

Differential plating medium for quantitative detection of histamine-producing bacteria.

A histidine-containing agar medium has been devised for quantitative detection of histamine-producing bacteria that are alleged to be associated with scombroid fish poisoning outbreaks. The responsible bacteria produce a marked pH change in the agar, with attendant color change of pH indicator adjacent to the colonies, thus facilitating their recognition. Proteus morganii and Klebsiella pneumoniae were the two most common histidine-decarboxylating species isolated from scombroid fish and mahi mahi.

Animals↗

Comparison of Vibrio cholerae O139 with V. cholerae O1 classical and El Tor biotypes.

Vibrio cholerae O139 is a recently identified non-O1 V. cholerae strain responsible for outbreaks of epidemic cholera in India, Bangladesh, and Thailand in the past 2 years. Other workers have demonstrated the presence of the cholera toxin genetic element in V. cholerae O139, unlike the situation for other non-O1 V. cholerae strains. We sought to compare further this strain with strains of V. cholerae O1, classical and El Tor biotypes, by classic microbiologic methods, Southern blot analysis for restriction fragment length polymorphisms with probes for iron-regulated genes of V. cholerae O1, and comparisons of outer membrane protein profiles. Our results were similar for V. cholerae O139 and the El Tor biotype of V. cholerae O1, with the exception of the constitutive expression in V. cholerae O139 of OmpS, an outer membrane protein that was maltose inducible in comparison strains of V. cholerae O1.

Bacterial Outer Membrane Proteins↗

Interaction of recombinant norwalk virus particles with the 105-kilodalton cellular binding protein, a candidate receptor molecule for virus attachment.

Norwalk virus (NV), responsible for outbreaks of acute gastroenteritis, comprises the species of the genus Norwalk-like viruses in the family Caliciviridae. Although the study of the molecular biology of NV has been hampered by a lack of culture systems or small experimental animal models, virus-like particles (VLPs) generated with recombinant baculoviruses harboring the capsid protein gene of NV provide a useful tool for investigating NV-cell interactions. In this study, the attachment of the recombinant VLPs derived from the Ueno virus (UEV), a strain belonging to the genogroup II NVs, to mammalian and insect cells was examined. Kinetic analyses of the binding of the recombinant VLPs of the UEV (rUEVs) to Caco-2 cells demonstrated that the binding was specific and occurred in a dose-dependent manner. Approximately 7.5% of the prebound rUEVs were internalized into the Caco-2 cells. Enzymatic and chemical modification of Caco-2 cell surface molecules suggested that the binding was directly mediated by a protein-protein interaction. A virus overlay protein-binding assay (VOPBA) indicated that rUEVs appeared to bind to a 105-kDa molecule, designated as the NV attachment (NORVA) protein. Furthermore, the assay indicated that its native conformational structure was indispensable for the binding activity. In Caco-2 cells, the NORVA protein was detected when VOPBA was carried out with the VLPs from Seto and Funabashi viruses, which are serologically different NVs from UEV, used as probes. The binding of rUEVs to NORVA protein was also observed in six mammalian cell lines other than Caco-2. These data suggest that the attachment of NV to mammalian cells is mediated by NORVA protein, which is ubiquitously expressed in the mammalian cells. The present study is the first report on the role of the cellular molecule in the binding of recombinant VLPs of NV.

Amino Acid Sequence↗

Equine infectious respiratory disease.

During the past 20 years the equine population of Great Britain and Ireland has increased with the result that the practising veterinary surgeon is more frequently called upon to advise on equine problems. A significant portion of this advice is concerned with the examination of horses showing signs of this advice is concerned with the examination of horses showing signs of respiratory disease. Numerous pathogens, which include viruses, bacteria, parasites and moulds invade the respiratory tract causing similar signs of illness. It is therefore difficult to provide an aetiological diagnosis based on a clinical examination. Field studies supported by laboratory investigations have established that influenza and herpes viruses are frequently responsible for outbreaks of disease. Epidemiological studies suggest that other factors including the immune state of the equine population influence the distribution and severity of respiratory disease. The aetiology, diagnosis, treatment and control of equine infectious respiratory disease are discussed below.

Abortion, Veterinary↗

Development of an astrovirus RT-PCR detection assay for use with conventional, real-time, and integrated cell culture/RT-PCR.

Astrovirus is a common cause of gastroenteritis in humans that has been determined to be responsible for outbreaks of illness in several countries. Since astrovirus can be waterborne, it is important to be able to identify this virus in environmental water. We have developed and optimized a reverse transcription - polymerase chain reaction (RT-PCR) method that was able to amplify all eight astrovirus serotypes in a single reaction. In addition, a positive control construct was designed so that any inhibitors of this astrovirus assay could be detected. The assay was adapted for use in a real-time PCR assay and the sensitivity of these two methods was compared. The real-time assay was then combined with CaCo2 cell culture to produce an integrated cell culture/RT-PCR (ICC/RT-PCR) assay that was able to detect low levels of astrovirus after an incubation of 7 days or less. Also, the sensitivity of the ICC/RT-PCR assay was compared with RT-PCR alone. The methods were used to detect astrovirus in acute phase illness stool samples as well as in a water sample spiked with astrovirus.

Caco-2 Cells↗

Neutralizing antibodies to enterovirus 71 in Belém, Brazil.

Non-polio enteroviruses (Coxsackievirus A, Coxsackievirus B, Echovirus and EV 68-72) which belong to the enterovirus (EV) genus, Picornaviridae family, may be responsible for acute flaccid paralysis, aseptic meningitis, myocarditis, hepatitis, pleurodinia, neonatal sepsis, hand, foot and mouth disease (HFMD) even though 50-80% of infections are asymptomatic. EV 71 has been responsible for outbreaks and epidemics of HFMD and acute neurologic disease justifying its study in our country. The aim of this study was to detect neutralizing antibodies (NtAb) to EV 71 in individuals up to 15 years of age living in Belém, State of Pará, northern Brazil. Serum samples from 238 patients attending the Virology Sector of Evandro Chagas Institute in Belém, Brazil, were analyzed using microneutralization tests that included RD cells and BrCr strain. Overall 40.8% (97/238) of tested samples had NtAb to EV 71. Regarding the distribution per age group, 85.2% (92/108) of patients aged 0-3 years had no NtAb to this virus and 69.2% of those 12 to 15 years of age were seropositive. These results confirm that EV 71 infection occurs in the city of Belém; and that a high rate of individuals in this study were infected aged 3 years and over and, when aged 15 years nearly 70% had EV 71 NtAb.

Adolescent↗

The development and validation of a geographic information system database for the poultry industry on the Delmarva Peninsula.

A geographic information system (GIS) database of the poultry industry on the Delmarva Peninsula was developed through a cooperative agreement between the Delmarva Poultry Industry, Inc., and the Virginia-Maryland Regional College of Veterinary Medicine. The purpose of this database was to facilitate disease surveillance and assist in managing the response to outbreaks and other emergencies. Two methods of data collection were employed and are described in this paper. The first method was to visit each poultry farm and collect the latitude and longitude coordinates with a handheld global positioning system unit. The second method used property ownership information, aerial photographs, and a GIS to determine the latitude and longitude of each poultry farm. There was no significant difference between the two methods in the accuracy of the results, but there was a large difference in the amount of time and money necessary to obtain the data. These findings indicate that whereas there are many ways to obtain accurate data for a GIS database, other factors may influence which method is chosen. A subset of farms contained within the database was visited to assess the accuracy of the locations contained within the database. Of the 240 farms visited for validation, 212 showed evidence of a functioning or previously functioning poultry operation. The corresponding error rate was 11%. This demonstrates the need to assure that the database is kept up to date to ensure that attrition among poultry growers is recorded. Several potential factors that might contribute to sources of error are discussed.

Agriculture↗

Cryptosporidium parvum: treatment effects and the rate of decline in oocyst infectivity.

Cryptosporidium parvum has become the focus of numerous studies on waterborne disease and transmission in response to outbreaks endangering populations worldwide. The Foci Detection Method-Most Probable Number Assay (FDM-MPN) is an in vitro cell culture method that has been developed and used to determine the quantity of infectious C. parvum oocysts. This research evaluated 2 vendor's producing oocysts, Sterling Parasitology Laboratory (SPL) and Pleasant Hill Farms (PHF) (now known as Bunch Grass Farms as of 12/03), classified as young (<30 days) and aged (>165 days), for comparison of treatments (bleach, antibiotic, no treatment) before cell culture, as well as an age study, to determine any lot-to-lot differences and vendor differences regarding the rate of decline in infectivity. Bleach treatment (0.525%) appeared to be the optimum method for the FDM-MPN with regards to maximum infectivity, efficient disinfection, with no visible antagonistic affects on the C. parvum oocysts. The age study revealed that lot-to-lot variability within each vendor stayed within 1 log10 difference, while the rates of decline in infectivity measured until 107 and 120 days of age when stored at 4 C for SPL and PHF were -0.016 and -0.014 log10 infectious oocysts/day, respectively. These results provide insight regarding C. parvum oocyst viability in a fecal population, as well as useful knowledge for further methods development.

Amphotericin B↗

Macrophage recruitment and activation: a model for comparing resistance to Salmonella enteritidis in different broiler breeds.

A model for comparing resistance to Salmonella Enteritidis was evaluated in different broiler breeds. The recruitment and phagocytic activity of peritoneal macrophages were assessed in three different broiler breeds (A, B and C) which are farmed world-wide. Assessment was performed after three days of intraperitoneal (i.p.) administration of 3% Sephadex G-200 (10 ml), initiated at twenty-one days of age, followed by contact with i.p. live S. Enteritidis (10 ml, 1.2 x 10(8) colony forming units/ml) for 45 min. Assessment included determination of the number of i.p. macrophages recruited, the number of i.p. phagocytized S. Enteritidis cells per macrophage, the levels of degranulated i.p. beta-glucuronidase and beta-galactosidase, and the count of surviving S. Enteritidis cells. Confirmation of the significance of the model was obtained by comparing resistance to field infection by S. Enteritidis in the three broiler breeds. The recruitment of i.p. macrophages in response to challenge with Sephadex and S. Enteritidis was significantly higher (P < 0.05) in birds of breed A (mean cumulative i.p. macrophage count, in 10 fields of microscopic slide smear magnified at x1,000, was equal to 81.7), compared to recruitment in birds of breed B (33.3) or breed C (41.2). The mean number of phagocytized S. Enteritidis cells per i.p. macrophage in birds of breed A (2.68) was significantly higher (P < 0.05) than in breed B (0.83) and insignificantly higher (P > 0.05) than in breed C (2.35). In addition, the highest level of recruitment and phagocytic activity of macrophages, in birds of breed A, was associated with a higher significant mean i.p. beta-glucuronidase activity (10,425.5 units/ml) than in breed B (3,438.2 units/ml) or breed C (3,356.94 units/ml) (P < 0.05). Moreover, birds of breed A demonstrated a higher mean i.p. beta-galactosidase activity (2.225 units/ml) than birds of breed B (0.852 units/ml) or breed C (1.852 units/ml) (P > 0.05). The higher level of recruitment and activity of i.p. macrophages and the higher rate of degranulation of i.p. enzymes in breed A were associated with a greater number of surviving i.p. S. Enteritidis cells. In response to outbreaks of S. Enteritidis in the field, the average mortality was significantly higher in flocks of breed A (3.2%) than in flocks of breed B (1.2%) or breed C (0.96%) (P < 0.05). These data provide an indication of the significance of the model in reflecting the differences in resistance of S. Enteritidis of broiler breeds reared in a farm environment.

Animals↗

Recovery of hepatitis A virus from a water supply responsible for a common source outbreak of hepatitis A.

An outbreak of hepatitis A occurred in a north Georgia trailer park served by a private well. Of 18 residents who were serosusceptible to hepatitis A virus (HAV), 16 (89%) developed hepatitis A. Well water samples were collected 3 months after illness onset in the index case and 28 days after illness onset in the last trailer park resident. Hepatitis A virus antigen (HAVAg) was detected in the samples by enzyme immunoassay from three of the five cell lines following two 30-day passages and from a fourth cell line following a third passage of 21 days.

Adult↗

Human West Nile virus lineage 2 neuroinvasive infection as a cause of fatal Guillain-Barr&#xe9; syndrome.

BACKGROUND: West Nile virus (WNV) is now endemic in Europe and continues to spread to several countries, with strains 1 and 2 primarily responsible for outbreaks. According to the European Centre for Disease Prevention and Control (ECDC), Italy accounts for the majority of locally acquired cases and West Nile neuroinvasive disease (WNND). CASE REPORT: We present the first case described in Italy and Europe of WNND-related Guillain-Barr&#xe9; syndrome (GBS). Phylogenetic analysis showed that the genome belonged to the WNV-2, sublineage 2a, clustering within sequences from genomes originating mainly from Hungarian 578/10 strain, a particularly virulent strain. CONCLUSION: The first case of GBS as a presentation of WNND in a European patient is reported, along with a review of all previously published cases of GBS related to WNND. The United States Centers for Diseases Control and Prevention (CDC) documented 13% of WNV infections manifest as GBS, with a gradual and slow improvement, often with residual neurologic deficits of varying severity. Physicians should be aware that the presentation of a patient to an emergency department with GBS, during a certain epidemiological period of the year, should raise the clinical suspicion that the GBS may be related to a WNND.

Humans↗