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A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants.

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease. Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented. Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined. None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40%. Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus. In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified. This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo. In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy. Possible modifications of the vaccine formulations to increase protective activity are discussed.

Amino Acid Sequence↗

Intranasal immunization of guinea pigs with an immunodominant foot-and-mouth disease virus peptide conjugate induces mucosal and humoral antibodies and protection against challenge.

Guinea pigs immunized intranasally with a keyhole limpet hemocyanin-linked peptide, corresponding to the prominent G-H loop of the VP1 protein of foot-and-mouth disease virus, raised substantial levels of antipeptide and virus-neutralizing antibodies in sera and of peptide-specific secretory immunoglobulin A in nasal secretions. In groups of animals immunized intranasally without adjuvant, 86 percent were fully protected upon challenge with homotypic virus. Surprisingly, animals given the peptide conjugates plus the mucosal adjuvant cholera toxin were afforded only partial protection in that primary lesions were observed in most animals, although spread to other feet was prevented. These results indicate that intranasal inoculation with the peptide offers a potential route of vaccination against foot-and-mouth disease and may be useful for eliciting protection in the upper respiratory tracts of susceptible animals.

Administration, Intranasal↗

Novel viral disease control strategy: adenovirus expressing alpha interferon rapidly protects swine from foot-and-mouth disease.

We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN-alpha/beta). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN-alpha or IFN-beta (Ad5-pIFNalpha or Ad5-pIFNbeta). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 10(9) PFU of a control Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed typical signs of foot-and-mouth disease (FMD), including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 10(9) PFU of Ad5-pIFNalpha were completely protected when challenged 24 h later with FMDV. These animals showed no clinical signs of FMD and no viremia and did not develop antibodies against viral nonstructural proteins, suggesting that complete protection from infection was achieved.

Adenoviridae↗

Candida in mouth or on dummy?

Mouth and dummy swabs for Candida spp. were obtained from 100 children under 18 months old admitted with acute medical conditions. Forty four per cent of dummies were colonised by Candida spp. Children who sucked dummies had clinical thrush and positive mouth swabs for candida more frequently than those who did not.

Candida↗

Psychosocial effects of the 2001 UK foot and mouth disease epidemic in a rural population: qualitative diary based study.

OBJECTIVES: To understand the health and social consequences of the 2001 foot and mouth disease epidemic for a rural population. DESIGN: Longitudinal qualitative analysis. SETTING: North Cumbria, the worst affected area in Britain. SAMPLE: Purposive sample of 54 respondents divided in six demographically balanced rural occupational and population groups. MAIN OUTCOME MEASURES: 3071 weekly diaries contributed over 18 months; 72 semistructured interviews (with the 54 diarists and 18 others); 12 group discussions with diarists RESULTS: The disease epidemic was a human tragedy, not just an animal one. Respondents' reports showed that life after the foot and mouth disease epidemic was accompanied by distress, feelings of bereavement, fear of a new disaster, loss of trust in authority and systems of control, and the undermining of the value of local knowledge. Distress was experienced across diverse groups well beyond the farming community. Many of these effects continued to feature in the diaries throughout the 18 month period. CONCLUSIONS: The use of a rural citizens' panel allowed data capture from a wide spectrum of the rural population and showed that a greater number of workers and residents had traumatic experiences than has previously been reported. Recommendations for future disaster management include joint service reviews of what counts as a disaster, regular NHS and voluntary sector sharing of intelligence, debriefing and peer support for front line workers, increased community involvement in disposal site or disaster management, and wider, more flexible access to regeneration funding and rural health outreach work.

Agricultural Workers' Diseases↗

Assessment of the reproducibility of the lactulose H2 breath test as a measure of mouth to caecum transit time.

The lactulose H2 breath test is in use as a simple non-invasive measurement of mouth to caecum transit time, but its reproducibility has never been assessed. We have examined the reproducibility of mouth to caecum transit time in 21 normal subjects using lactulose 10, 15, and 20 g; seven subjects being studied with 10 g and 12 each with 15 and 20 g doses. Transit time decreased with increasing doses of lactulose although the differences were not significant between or within (n = 5) individuals. Variation in transit times between individuals was considerable with all doses of lactulose (mean coefficient of variation of 18.5, 29.7 and 28.3% with 10, 15, and 20 g respectively). The addition of lactulose to a liquid meal containing carbohydrate, fat, and protein decreased the coefficient of variation to less than 10% in four subjects studied. The lactulose H2 breath test could be made more reproducible by including a liquid meal.

Adult↗

Candidal infections and populations of Candida albicans in mouths of diabetics.

The prevalence of oral candidosis and the frequency of isolation of Candida albicans and its density and distribution have been determined in the mouths of 50 patients with diabetes mellitus and 50 healthy volunteers matched for age, sex, dental status and smoking habits. Three of the diabetic patients were found to have a chronic oral candidosis. According to an imprint culture technique, the oral carrier rate and density of C albicans were both higher in the diabetic group as a whole than in the control subjects. Smoking was associated with an increased prevalence of the yeast in diabetes mellitus. Diabetics wearing dentures had higher candidal density than those without a prosthesis. No differences in candidal status could be detected according to the degree of control of diabetes, mode of treatment, duration of diabetes or the patient's age. Local factors such as smoking and the presence of dentures, particularly when worn continuously, interact with diabetes mellitus in promoting candidal colonisation of the mouth. Attention to these predisposing factors could reduce the incidence of thrush in diabetics.

Adolescent↗

Identification of Helicobacter pylori DNA in the mouths and stomachs of patients with gastritis using PCR.

AIMS: To determine the prevalence of Helicobacter pylori colonisation in the mouths of patients with H pylori gastritis. METHODS: A nested polymerase chain reaction test for the 16S ribosomal RNA gene of H pylori was used on saliva, dental plaque, gastric juice and gastric biopsy specimens from patients attending a dyspepsia clinic. RESULTS: Thirteen patients had histologically confirmed Helicobacter associated gastritis. Twelve of these had positive gastric aspirates by PCR. Five had at least one positive oral specimen. Eight patients with normal gastric biopsy specimens had no PCR positive oral specimens or gastric aspirates. All, however, had PCR positive gastric biopsy specimens. In an attempt to determine the origin of these positive results in normal patients, it was shown that biopsy forceps could contaminate specimens with DNA from previous patients. CONCLUSION: The demonstration of the organism in the mouths of a substantial proportion of dyspeptic patients has major implications for the spread of H pylori and identifies a potential source for reinfection following eradication of the organism from the stomach.

Base Sequence↗

Measurement of sniff nasal and diaphragm twitch mouth pressure in patients.

BACKGROUND: Inspiratory muscle weakness is a recognised cause of unexplained dyspnoea. It may be suggested by the finding of a low static inspiratory mouth pressure (MIP), but MIP is a difficult test to perform, with a wide normal range; a low MIP may also occur if the patient has not properly performed the manoeuvre. Further investigation conventionally requires balloon catheters to obtain oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic nerve stimulation. Two non-invasive tests of inspiratory muscle strength have recently been described--nasal pressure during a maximal sniff (Sn Pnas) and mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The use of these two tests in combination might identify patients without inspiratory muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding the need for investigation with balloon catheters. METHODS: Thirty consecutive patients with clinically suspected inspiratory muscle weakness and a low MIP underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or = 80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20. RESULTS: Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of these would have been identified using Sn Pnas and Tw Pmo, with better results when the two tests were combined. The cut off values selected for Sn Pnas and Tw Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding failure to detect mild degrees of weakness. No patient with global weakness was considered normal by Sn Pnas or Tw Pmo. CONCLUSIONS: In most patients with normal inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can reliably exclude global inspiratory muscle weakness, reducing the number of patients who need testing with balloon catheters.

Adult↗

Experimental foot-and-mouth disease in fattening pigs, sows and piglets in relation to outbreaks in the field.

The progression of foot-and-mouth disease in sows and their litters of piglets following exposure to O1 Lausanne virus has been investigated. The majority of piglets died with acute myocarditis but without developing vesicles. Deaths occurred before and also when sows began showing early evidence of vesicle formation. This clinical picture parallels that seen at the beginning of both the Normandy 1979 and Britanny 1981 epidemics in France and points to the necessity of including foot-and-mouth disease in the differential diagnosis of acute death among cloven-hoofed livestock and furthermore the importance of extending clinical inspections to adult animals on premises when such events take place. In investigations in which the susceptibility of fattening pigs to infection with O1 Lausanne virus given by the intramuscular route was examined it was found that the 50 per cent infective dose was log (10)4.8 TCID50. This finding suggests that large amounts of virus are required for successful initiation of disease. This is more likely to come from animals already infected than by inoculation with contaminated material.

Acute Disease↗

Experimental transmission of foot-and-mouth disease virus from carrier African buffalo (Syncerus caffer) to cattle in Zimbabwe.

Four female cattle and three male African buffalo (Syncerus caffer) which were free of foot-and-mouth disease (FMD) virus were held together on an island in Lake Kariba, Zimbabwe. The buffalo were experimentally infected with FMD virus type SAT2, developed generalised disease and became virus carriers. While the buffalo were in the acute phase of the disease the susceptible contact cattle did not show lesions, no virus was recovered from them and they did not develop serum antibodies. However, five months later the cattle developed severe foot-and-mouth disease. Direct nucleotide sequencing of the virus used to infect the buffalo and of the virus from the in-contact cattle showed that the two isolates were almost identical. The results suggest that in nature it is possible for the virus to be transmitted from buffalo to cattle under the influence of factors not yet defined, and that there was very little change in the nucleotide sequence of the virus during the carrier period of five months.

Amino Acid Sequence↗

Infectivity assays of foot-and-mouth disease virus: contact transmission between cattle and buffalo (Bubalus bubalis) in the early stages of infection.

No differences were observed between cattle and Indian buffalo (Bubalus bubalis) in terms of temperature, viraemia or virus replication in the pharyngeal area, during the acute phase of foot-and-mouth disease. Like cattle, the Indian buffalo became infected and excreted virus before any clinical signs of foot-and-mouth disease developed. The disease was transmitted from cattle to buffalo and vice versa, during the acute stage of infection, as if the animals had been of the same species, presumably because of their close phylogenetic relationship. There were more tongue lesions in the cattle than in the buffalo. Foot lesions in the buffalo at first had a scaley appearance, but later became vesicular. Anti-virus infection associated antigen and neutralising antibodies were synthesised at the same time in both species and reached similar titres in the same period. Persistent infection in the buffalo during the first 35 days after infection was similar to that in the cattle.

Animals↗

Defining the normal temporomandibular joint: closed-, partially open-, and open-mouth MR imaging of asymptomatic subjects.

Fifty temporomandibular joints (TMJs) in 30 asymptomatic volunteers were imaged with a 1.5-T magnetic resonance (MR) imaging system to determine (a) the normal range of meniscus position, (b) the best definition of a normal TMJ and criteria to distinguish it from a TMJ with significant internal derangements, (c) the significance of certain findings such as joint effusion and disk distortion, and (d) the optimum mouth position(s) to be used for imaging. A method was devised to quantify meniscus displacement in terms of the number of degrees from a 12 o'clock or vertical position (relative to the condyle). The distribution of meniscus positions defined two groups in this asymptomatic study group. A strong correlation between abnormal joints and a history of orthodontics led to the exclusion of subjects with a history of orthodontics, and those with mouth trauma were also excluded, leaving a better "normal control" group. The junction of the posterior band of the meniscus and the bilaminar zone should fall within 10 degrees of vertical to be within the 95th percentile of normal.

Cartilage, Articular↗

Respiratory transfer impedances with pressure input at the mouth and chest.

Two methods of measuring respiratory transfer impedance (Ztr) were compared in 14 normal subjects, from 4 to 30 Hz, 1) studying the relationship between transrespiratory pressure (Prs) and flow at the chest when varying pressure at the mouth (Ztrm) and 2) studying the relationship between Prs and flow at the mouth when varying pressure around the chest wall (Ztrw). The similarity of the two relationships was expected on the basis of a T-network model. Almost identical phase responses were obtained from the two methods. Pressure-flow ratios were slightly larger for Ztrw than for Ztrm, but differences did not exceed 2% on average in 11 of 14 subjects. When the data were analyzed with the six-coefficient model proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), similar values were found for tissue compliance and tissue inertance but slightly different values for gaseous inertance in the airways (1.97 +/- 0.35 X 10(-2) cmH2O X l-1 X s2 for Ztrw vs. 1.73 +/- 0.26 for Ztrm; P less than 0.01). Similar results were also found for total respiratory resistance but with a slightly larger contribution of airway resistance for Ztrw (64 +/- 14 vs. 57 +/- 10%; P less than 0.05). As a practical conclusion it is recommended to measure Ztrw, which is technically much easier.

Adult↗

Transmission to the chest of sound introduced at the mouth.

We examined the transmission to the chest wall of white noise and 25-Hz square-wave-generated noise introduced at the mouth of five healthy subjects. The output audio signals were recorded over the left and right upper and lower lung zones, posteriorly. Sound measurements were made during apnea at functional residual capacity, total lung capacity, and residual volume both after breathing air and an 80% He-20% O2 (heliox) gas mixture. We calculated the peak-to-peak amplitude, the peak frequency, and the midpower frequency of the output sound. We found no consistent variations in the values of these indexes due to lung volume or resident gas density. In all cases, the transmitted sound was most intense at the right upper zone. This could not be explained on the basis of technical factors but was probably the result of normal asymmetry of the mediastinal anatomy. These data suggest that sound introduced through the mouth of healthy individuals excites intrathoracic structures but is transmitted through the parenchyma in such a manner that it is not markedly affected by familiar physiological variables. This must be taken into account if objective acoustical tests of lung physiology are to be developed.

Adult↗

Effect of a logopedic instruction program after adenoidectomy on open mouth posture: a single-blind study.

The effect of adenoidectomy (controls) on habitual open mouth posture was compared with adenoidectomy in combination with a logopedic instruction program (cases). One hundred and fifty-nine children were included (aged 2-10 years, mean age 4.6 years). The instruction program consisted of three individual logopedic sessions at 1 week, 2 weeks and 4 weeks postoperatively. One week preoperatively, 2 months and 1 year postoperatively an estimation of open mouth posture was carried out. Two months postoperatively there was a significant difference between the two groups (p = 0.001), but 1 year postoperatively this difference had disappeared (p = 0.526). The logopedic instruction program was not effective for the youngest age-group (<3.6 years).

Adenoidectomy↗

Hand, mouth and eye preferences in the common marmoset (Callithrix jacchus).

Motor and sensory preferences were measured for 8 common marmosets (Callithrix jacchus). Three types of motor function were examined: spontaneous feeding, mouth use when chewing and visuospatial reaching. Eye preference was used as an index of sensory lateralization. The marmosets displayed individual preferences for the performance of the motor tasks, but no group biases were revealed. Correlations between preferences displayed on the motor tests suggest that one hemisphere may control spontaneous feeding and lateralized mouth use while the other controls visuospatial reaching, but no consistent preference was present. In an eye preference test, 7 subjects displayed right-eye preferences, suggesting hemispheric specialisation for this function.

Animals↗