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A 'new' generation of more potent synthetic antirhinovirus compounds: comparison of their MICs and their synergistic interactions.

A 'new' generation of synthetic antirhinovirus compounds has recently become available for in vitro evaluation. Thus a new group of compounds from Janssen was found to be 10-fold more active than enviroxime or 57-fold more active than dichloroflavan (DCF), against human rhinovirus 9 (HRV-9). In addition, they were also some 5- and 10-fold more potent than enviroxime and DCF, respectively, against HRV-2. Similarly, a 'new' series of antirhinovirus compounds from Roche, although as active as enviroxime against HRV-9, were found to be 4-fold more potent than DCF against the same virus. Moreover, they were 45- and 90-fold more active than enviroxime and DCF, respectively, when tested against HRV-2. We found that generally HRV-2 was more sensitive to these new compounds than HRV-9. In this study we also report on the synergistic interaction between these new synthetic substances and also with some of the earlier compounds such as DCF and enviroxime and we discuss the possible implication of this synergistic activity regarding the future prevention and treatment of common colds caused by rhinoviruses.

Antiviral Agents↗

Infectious triggers of pediatric asthma.

Respiratory infections can cause wheezing illnesses in children of all ages and also can influence the causation and disease activity of asthma. For years it has been recognized that respiratory syncytial virus infections often produce the first episode of wheezing in children who go on to develop chronic asthma. More recently, it has been proposed that repeated infections with other common childhood viral pathogens might help the immune system develop in such a way as to prevent the onset of allergic diseases and possibly asthma. In addition to the effects of viral infections, infections with certain intracellular pathogens, such as chlamydia and mycoplasma, may cause acute and chronic wheezing in some individuals, whereas common cold and acute sinus infections can trigger acute symptoms of asthma. In this article, the epidemiologic, mechanistic, and treatment implications of the association between respiratory infections and asthma are discussed.

Asthma↗

Respiratory syncytial virus epidemiology in Turkey.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children worldwide. This study was conducted to determine the prevalence of RSV among high-risk children admitted with respiratory symptoms in a developing country. This is a multicenter study conducted among children less than 24 months of age and admitted to the hospital with respiratory symptoms. The inclusion criteria included: lower respiratory tract symptoms on admission, gestational age less than 35 weeks, and admission age less than six months, or children less than 24 months of age with a diagnosis of bronchopulmonary dysplasia requiring medical treatment or intervention during the last six months or with an uncorrected congenital heart disease (other than patent ductus arteriosus). Nasopharyngeal samples were obtained with one of the three standard methods: nasopharyngeal aspirate, nasopharyngeal wash or nasopharyngeal swab. RSV antigen was determined by enzyme immunoassay using Abbott TESTPACK RSV (No. 8100/2027-16). Statistical analysis was performed using Student's t-test and chi-square test. In this study, 332 children (135 females, 40.7%; 197 males, 59.3%) were included, and the nasopharyngeal specimens of 98 (29.5%) children were determined to be RSV-positive. There were no differences in sex, age of gestation, age of admission, family education, number of siblings and smoking at home for RSV-positive and -negative cases. Furthermore, underlying disease and duration of hospital and intensive care unit stay were similar among groups. Only otitis media was more common among RSV-positive cases. No fatality at hospital was recorded. Frozen samples revealed more negative results. Most cases presented during winter and the number of RSV-positive cases was higher in cold and economically poor areas. Premature children and children with underlying medical condition acquire RSV irrespective of other sociodemographic risk factors, and most of them are hospitalized. Thus, an RSV vaccine seems the most effective mode of protection to decrease morbidity and mortality.

Comorbidity↗

An investigation of the immune response of patients suffering from anorexia nervosa.

Patients suffering from anorexia nervosa rarely appear to develop the common cold or influenza. This study examines the immunological response of fifteen female anorexia nervosa patients of both the vomiting and carbohydrate-abstaining type and compares them with a control population matched for age and occupation. Both anorectics and control populations received the admune influenza vaccine. Initially both groups had similar haemagglutination inhibition titres against the three different viral antigens: A/HK; A/PC; A/Eng. However, the anorectics showed over a 2-month period a higher titre of antibody especially to the Hong Kong virus: this was sigignificant. Cellular immune responses were measured using a tuberculin and a macrophage inhibition test, no significant difference between the two groups was obderved. These results which support the clinical findings are discussed.

Adolescent↗

[HTLV-I seronegative idiopathic progressive spastic paraparesis: clinical and neurophysiological study of the sensory features].

BACKGROUND: HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a defined entity. However, there are many patients not well characterized with a similar clinical picture who are HTLV-I seronegative. OBJECTIVE: Clinical and neurophysiological description of patients with HTLV-I seronegative idiopathic paraparesis. PATIENTS AND METHODS: Seventeen patients (4 women and 13 men aged 24-67 years, average 52.3) were evaluated including clinical assessment, vibratory sensory analysis, quantitative somatosensory thermotest (QST), somatosensory evoked potentials (SSEPs), electromyography (EMG) and motor and sensory nerve conductions. RESULTS: In addition to the spastic paraparesis, 3 (17.6%) patients had pseudobulbar symptoms. Ten (58.8%) patients had a spastic gait but could walk unaided, 6 (35.2%) needed support and 1 patient could not walk. Bladder dysfunction was found in 10 (58.8) patients and sensory symptoms in 7 (41.1%). There was mild distal impairment of vibration and position sense, distal tactile and pinprick hypoesthesia in 4 (23.4%) patients. Tibial SSEPs were abnormal in 11 (64.7%). Nerve conduction studies and EMG were normal. QST showed cold hypoesthesia in 14 (82.4%) patients. Warm sensation and beat pain appeared unimpaired. CONCLUSIONS: All sensory abnormalities found were restricted to sensations carried by myelinated (A beta and A delta) channels. Sensory and motor abnormalities are similar to HAM/TSP patients suggesting a common pathogenesis.

Adult↗

[A steroid-responsive case of severe rhabdomyolysis associated with cytomegalovirus infection].

A 31-year-old man was admitted to our hospital, complaining of muscular weakness and pain in the legs one month after a common cold. On admission, neurological examinations demonstrated moderate weakness in the arms and mild weakness in the legs with decreased or diminished deep tendon reflexes, and mild dysphagia. Weakness was gradually extended to the arm, throat and respiratory muscles, requiring artificial ventilation. Laboratory examinations demonstrated increased levels of CK (upto 24,380 IU/L) and positive anti-cytomegalovirus (CMV) -IgM antibodies in the serum, and myogloburinuria. CMV was not detected in either the blood cells or muscles by PCR. There were no antibodies against viruses including Ebstein-Barr virus and HIV, in the serum. There were no autoantibodies related to collagen diseases in the serum. Systemic PET scan did not show any evidence of malignancy. Bone marrow biopsy did not show any atypical cells. Muscle MRI demonstrated mild atrophy with high intensity signals in part. Muscle biopsy demonstrated scattered necrotic and regenerated muscle fibers without inflammatory cell infiltration. The patient was therefore diagnosed as having rhabdomyolysis associated with CMV infection. After three courses of intravenously administered high dose methylprednislone over three days, muscle weakness improved gradually, and the serum CK level was normalized in two months. The patient recovered and was removed from artificial ventilation three months after the therapy. There were no sign of renal failure. Steroid therapy should be considered for the treatment of rhabdomyolysis or myopathy associated with CMV infection in order to prevent renal failure or fatal progression of the disease.

Adolescent↗

A double-blind, placebo-controlled clinical trial of the effect of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge.

This paper presents the results of a randomized, double-blind, placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus "common cold." Forty healthy, adult, nonatopic subjects were randomly assigned to one of two treatment groups: active drug and placebo. On study Day 0, all subjects were challenged intranasally with rhinovirus type 39 (dose = 100 TCID50). Subjects were cloistered from Day 2 to Day 7, at which time they were treated with either chlorpheniramine or placebo. From 3 days before challenge to study Day 19, subjects had nasal patency assessed by rhinomanometry, eustachian tube function assessed by the 9-step test and sonotubometry, middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique. Symptom diaries were maintained throughout the period of follow-up. During cloister, symptoms also were scored by interview, nasal secretions were quantified and nasal washings were performed for viral culture. Results showed that 19 (95%) subjects in the active-treatment group and 18 (90%) subjects in the placebo-treatment group shed virus. Symptomatic colds were observed in 63% of the active-treated and 83% of the placebo-treated subjects. Symptoms increased on Day 1 and peaked at Days 4 to 5. Detrimental changes in other measured functions consistent with those previously reported were observed. During the period of treatment, significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing. Also, weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group. No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented.

Acoustic Impedance Tests↗

Human CD8+ CTL recognition and in vitro lysis of herpes simplex virus-infected cells by a non-MHC restricted mechanism.

Cytotoxic T lymphocytes (CTL) are important for the recognition and lysis of virally infected cells, but their effectiveness can be limited by viral immune evasion mechanisms. We investigated the immunophenotype and function of human CD8+ T cells raised in response to herpes simplex virus (HSV). The expanded population contained cells of an activated and mature phenotype, as determined by the expressions of CD25, CD45RO, CD57, CD95 and HLA-DR. Cultured cells also expressed CD45RA. These cells lysed autologous and allogeneic HSV-infected lymphoblastoid cell line (LCL) targets via a non-major histocompatibility complex (MHC) restricted recognition pathway. Inhibition assays showed the mechanism of cytotoxicity to be calcium-dependent, granule exocytosis pathway, rather than the internal disintegration pathway. Cold target competition assays indicated that a common CTL population contributed to the recognition of autologous and allogeneic-infected targets. These effectors showed recognition of infected targets which was distinct from that of K562 cells. Non-MHC restricted lysis-associated molecule 2B4 (CD244) was upregulated on culturing and made a significant contribution to lysis of FcgammaR-bearing targets in a redirected killing assay. These findings suggest that CTL can recognize virally infected cells through a combination of non-MHC restricted mechanisms and may result in more efficient lysis than classical CD8+ T cells.

Antigens, CD↗

Oral antibiotic use without consulting a physician: a survey of ED patients.

The purpose of our study was to determine the extent to which patients use antibiotics without consulting a physician and to examine patient characteristics associated with such oral antibiotic misuse. The study design was a prospective survey. The setting was a suburban, community, emergency department (ED). The participants were a convenience sample of oriented, ED patients who were enrolled during an 8-week period. Subjects provided written answers to standardized questions regarding their use of oral antibiotics over the 12 months preceding their ED visit. Categorical and continuous data were analyzed by chi-square and t-tests respectively. All test were 2-tailed with alpha set at 0.05. One thousand three hundred sixty three subjects were enrolled; 80% were White, 54% were female, 58% had attended college, 85% had a private physician, and 88% had health insurance. The mean age was 45 +/- 19 years. 43% of patients had used oral antibiotics within the past year. Twenty-two percent of patients indicated that their physicians routinely prescribed antibiotics for their cold symptoms. Seventeen percent of patients had taken "left-over" antibiotics without consulting their physician, most commonly for a cough (11%) or sore throat (42%), and much less frequently for urinary tract infection symptoms (0.7%). Women (19% versus 15% men; P =.04) and patients who attended college (19% versus 14% no college; P =.01) were more likely to have taken "left-over" antibiotics. A significant percentage of our ED patients had taken oral antibiotics without consulting a physician for symptoms frequently caused by viruses. Further study is warranted to examine whether local patterns of outpatient self-prescribing affect community oral antibiotic resistance.

Administration, Oral↗

T lymphocyte tolerance and early appearance of virus-induced cell surface antigens in Moloney-murine leukemia virus neonatally injected mice.

Regression of Moloney-murine sarcoma virus- (M-MSV) induced sarcomas in normal adult mice is accompanied by generation of virus-specific cytotoxic T lymphocytes (CTL). However, when neonatal mice that were injected with Moloney-murine leukemia virus (M-MuLV carrier) were subsequently challenged as adults with M-MSV, the sarcomas did not regress nor did they generate CTL. This failure to produce CTL cannot be ascribed to nonspecific immunodepressive effects or to suppressor cell generation since M-MuLV carrier mice exhibit normal reactivity after allogeneic cell stimulation. Moreover, addition of M-MuLV-infected cells as the third party to cultures does not reduce activity of CTL from M-MSV immune mice. Since M-MSV and M-MuLV possess common antigens, the observed unresponsiveness was considered in relationship to induction of a T lymphocyte tolerance, which may follow introduction of foreign antigens at an early stage of development. In fact, it was observed that as early as 10 days after injection, thymus, lymph node, and spleen from M-MuLV carrier mice express virus-induced cell-surface antigens that not only are targets for M-MSV-immune CTL, but also induce in vitro a strong specific cytotoxic response. In addition, a cold target inhibition assay disclosed that the same antigens are shared by both M-MuLV infected and leukemia cells, even though they are less expressed on the surface of the former. The finding that the cytotoxicity of alloreactive lymphocytes from M-MuLV carrier mice is reduced after preincubation with M-MSV immune CTL confirms that virus infection does not bring about functional inactivation of lymphocytes. Finally, it was observed that virus antigen presence on lymphocytes from M-MuLV neonatally injected mice is closely related to subsequent leukemia development.

Animals↗

Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.

AIM: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. METHODS: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre. RESULTS: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level. CONCLUSIONS: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further.

Asbestos↗

Capillary electrophoresis of affinity complexes between subviral 80S particles of human rhinovirus and monoclonal antibody 2G2.

Human rhinoviruses (HRVs), the main etiologic agents of the common cold, transform into subviral B- or 80S particles (they sediment at 80S upon sucrose density gradient centrifugation) during infection and, in vitro, upon exposure to a temperature between 50 and 56 degrees C. With respect to the native virion they lack the genomic RNA and the viral capsid protein VP4. 80S particles are unstable and easily disintegrate into their components, VP1, VP2, and VP3 in buffers containing SDS. However, this detergent was found to be a necessary constituent of the BGE for the analysis of these viruses and their complexes with receptors and antibodies by CE. We here demonstrate that dodecylpoly(ethyleneglycol ether) (D-PEG) a nonionic detergent, is suitable for analysis of subviral particles as it preserves their integrity, in contrast to SDS. Electrophoresis of the 80S particles in borate buffer (pH 8.3, 100 mM) containing 10 mM D-PEG resulted in a well-defined electrophoretic peak. The identity of the peak was confirmed, among other means, by complexation with mAb 2G2, which recognizes a structural epitope exclusively present on subviral particles but not on native virus. Upon incubation of the 80S particles with mAb 2G2 the peak disappeared, but a new peak, attributed to the antibody complex emerged. The separation system allowed following the time course of the transformation of intact HRV serotype 2 into 80S particles upon incubation at temperatures between 40 and 65 degrees C. We also demonstrate that subviral particles derived from HRV2 labeled with the fluorescence dyes FITC or Cy3.5 were stable in the separation system containing D-PEG. Dye-modified particles were still recognized by mAb 2G2, suggesting that the exposed lysines that are derivatized by the reagent do not form part of the epitope of the antibody.

Antibodies, Monoclonal↗

Human rhinovirus 3 at 3.0 A resolution.

BACKGROUND: The over 100 serotypes of human rhinoviruses (HRV) are major causative agents of the common cold in humans. These HRVs can be roughly divided into a major and minor group according to their cellular receptors. They can also be divided into two antiviral groups, A and B, based on their sensitivity to different capsid-binding antiviral compounds. The crystal structures of HRV14 and HRV16, major-receptor group rhinoviruses, as well as HRV1A, a minor-receptor group rhinovirus, were determined previously. Sequence comparisons had shown that HRV14 seemed to be an outlier among rhinoviruses. Furthermore, HRV14 was the only virus with no cellular 'pocket factor' in a hydrophobic pocket which is targeted by many capsid-binding antiviral compounds and is thought to regulate viral stability. HRV3, another major-receptor group virus, was chosen for study because it is one of a subset of serotypes that best represents the drug sensitivity of most rhinovirus serotypes. Both HRV3 and HRV14 belong to antiviral group A, while HRV16 and HRV1A belong to antiviral group B. RESULTS: HRV3 was found to be very similar to HRV14 in sequence and structure. Like HRV14, crystallized HRV3 also has no bound pocket factor. The structure of HRV3 complexed with an antiviral compound, WIN56291, was also determined and found to be similar to the same antiviral compound complexed with HRV14. CONCLUSIONS: The amino-acid sequence and structural similarity between HRV3 and HRV14 suggests that rhinoviruses in the same antiviral group have similar amino-acid sequences and structures. The similar amino-acid composition in the pocket region and the viral protein VP1 N termini in all known group B HRV sequences suggests that these viruses may all contain pocket factors and ordered N-terminal amphipathic helices in VP1. Both of these factors contribute to viral stability, which is consistent with the observations that group B rhinoviruses have a higher chance of successful transmission from one host to another and is a possible explanation for the observed higher pathogenicity of these rhinoviruses.

Antigens, Viral↗

DNA probe for the human coronavirus OC43 also detects neonatal calf diarrhea coronavirus (NCDCV).

Human coronaviruses (HCV) OC43 and 229E are the second most frequently isolated agents of common colds, and have also been associated with severe upper respiratory infections in children and with gastroenteritis of unknown etiology, such as infantile necrotizing enterocolitis. While HCV-OC43 and neonatal calf diarrhea coronavirus NCDCV cannot be held responsible for enteric infection in man, serological data suggest the possible existence of a human coronavirus, antigenically related to HCV-OC43 and NCDCV, and responsible for enteric infections. We developed a rapid and sensitive method for the diagnosis of the human respiratory coronavirus infections, and for detecting these viruses in suspect coronavirus infections. This assay entails a reverse transcriptase polymerase chain reaction, followed by Southern blot analysis with a probe specific for the amplification products.

Blotting, Southern↗

[Epidemiology, clinical picture, prevention and treatment of Avian influenza].

Current data concerning epidemiology, clinical picture, pathogenesis, prevention and treatment of Avian influenza H5N1, data of pharmacodynamics and pharmacokinetics of antiviral drugs--neuraminidase inhibitors and M2 channels inhibitors, also the recommendation of WHO for prevention prevalence of infection were discussed in the review. Strategic measures of WHO aims to protect humans from contact with infected poultry, in case of contact, to prevent transmission of this infection from human to human and occurrence of pandemic. Infected birds were the major source of the H5N1 influenza virus among humans in Asia. Mainly humans became infected by eating infected birds, by poor hygiene procedures when cooking infected birds, or by close contact with infected poultry. At present transmission of the H5N1 influenza from human to human by aerosol way hasn't been registered, but ongoing monitoring for identification mutation and adaptation of H5N1 influenza virus to human is needed. Season influenza and avian H5N1 influenza differ by the ways of transmission, clinical picture, severity, pathogenesis, response to treatment. Diagnostic of infection is difficult due to non-specific initial symptoms, in most cases disease begins with disturbance of under respiratory ways and in rare cases--from upper respiratory ways. High viral titre is identified in pharynx but not in nose. Initial symptoms of the H5N1 influenza are: fever greater then 38 degrees Celsius, mild cold, cough and shortness of breath, practically all patient have viral pneumonia, later secondary bacterial infection occurs, mild to severe respiratory distress, diarrhea, vomiting and abdominal pain. Conjunctivitis is rarely diagnosed contrary to season influenza. Sometimes gastrointestinal disorder begins a week early then respiratory symptoms. Complication also includes renal and multi organ failure. The cytokine storm is commonly developed during H5N1 influenza. For treatment and for prevention (under certain conditions) of the H5N1 influenza neuraminidase inhibitors such as oseltamivir (Tamiflu) and zanamivir (Relenza) are recommended. Currently circulatory of the H5N1 strains are fully resistant to an older class of antiviral drugs--the M2 channels inhibitors (amantadine and rimantadine). The knowledge of epidemiology, pathogenesis, clinical picture, treatment of the H5N1 influenza in humans, in spite of progress isn't complete. Future coordination of scientific investigation of the H5N1 influenza in humans should be provided not only in the countries where infection was revealed, but all around the world.

Acetamides↗

Fish rhabdovirus replication in non-piscine cell culture: new system for the study of rhabdovirus-cell interaction in which the virus and cell have different temperature optima.

The replication of three rhabdoviruses associated with diseases of fish has been demonstrated in cells of continuously cultivated non-piscine cell lines. Spring viremia of carp (SVC) virus and the salmonid fish viruses, Egtved and infectious hematopoietic necrosis virus, all replicated in mammalian WI-38 (human diploid cell strain) and BHK/21 cells and in cells of one or more reptilian cell lines at the temperatures commonly used to propagate these viruses in fish cells. The infections were cytopathic: SVC virus plaque assays may be performed in several types of mammalian cell culture. "Autointerference" apparently mediated by abortive "T" particle formation was observed during serial nondiluted passages of SVC virus in BHK/21 and TH1 cells, but not in RTG-2 or WI-38 cells. Optimal temperatures for replication of SVC and Egtved viruses in BHK/21 cells were identical to those determined in poikilothermic vertebrate cell cultures. However, these viruses replicated relatively more efficiently at suboptimal temperatures in "cold-blooded" vertebrate cells than in the hamster cells. Studies of [(3)H]uridine incorporation into uninfected BHK/21 cells incubated at different temperatures revealed that [(3)H]uridine uptake is sharply reduced at temperatures below 24.5 C. Growth curve studies of SVC virus in BHK/21 cells incubated at 23 C revealed that a clear-cut large excess of virus-induced [(3)H]uridine incorporation could be demonstrated in the absence of actinomycin D. Actinomycin D treatment (1 mug/ml) led to efficient inhibition of control cell [(3)H]uridine uptake, but also markedly reduced the total counts per minute of virus-induced [(3)H]uridine uptake, without depressing the yield of released infectious virus. Actinomycin D added to SVC virus-infected BHK/21 cell cultures at concentrations as low as 0.01 mug/ml caused a significant decrease in the level of virus-induced [(3)H]uridine uptake, despite the fact that this concentration is insufficient to efficiently suppress "background" cellular [(3)H]uridine incorporation.

Animals↗

Intranasal lymphoblastoid interferon ("Wellferon") prophylaxis against rhinovirus and influenza virus in volunteers.

Purified lymphoblastoid interferon (HuIFN-alpha) or placebo was self-administered intranasally by volunteers using a spray device three times daily for four and one-third days beginning one day before virus challenge. Each subject received a total dose of 35.1 Mu of interferon (IFN) administered in 13 equal doses of 2.7 Mu. Doses were administered in a volume of 0.2 ml (0.1 ml to each nostril). The first group received human rhinoviruses types 9 and 14. There were no significant colds in 19 volunteers receiving IFN and 7 in 23 volunteers receiving placebo (p less than 0.05). Serological responses and/or recovery of challenge virus were obtained in 14 (74%) recipients of IFN and in all 23 recipients of placebo (p less than 0.05). Mean daily and total clinical scores and mean daily and total nasal secretion weights were significantly greater in those receiving placebo than in those given IFN. The second group received influenza virus A/Eng/40/83. There were 4 significant illnesses in 13 volunteers receiving IFN and 10 in 17 volunteers receiving placebo (p greater than 0.05). Serological responses and/or recovery of challenge virus were obtained in 11 volunteers receiving IFN and 14 volunteers receiving placebo. Mean daily secretion weight and mean clinical scores were lower in those given IFN than in those given placebo - the differences were significant for clinical score on 2 days. The results suggest that IFN prophylaxis was less effective against influenza A than against rhinovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation of cold-recombinant influenza A/Korea (CR-59) virus vaccine in infants.

Twenty-four infants 5 to 13 months of age were intranasally vaccinated with a live cold-recombinant influenza A/Korea (CR-59, H3N2) virus vaccine. Nineteen infants served as controls. The inocula ranged from 10(3.2) to 10(6.2) 50% tissue culture infective doses (TCID50) per infant. Zero of six, one of four, seven of ten, and four of four infants receiving 10(3.2), 10(4.2), 10(5.2), and 10(6.2) TCID50, respectively, were infected by the intranasal vaccine. The amount of virus required to infect 50% of infants was calculated to be 10(4.6) TCID50. The occurrence of fever, respiratory illness, and otitis media was common among both controls and vaccinees in the postinoculation period. Maternal antibody was present in low titers in some infants and did not inhibit replication of the vaccine virus.

Administration, Intranasal↗