Respiratory Tract Mucosa Research Articles

Monkeypox Virus Infections

Monkeypox is an uncommon viral zoonosis caused by the monkeypox virus (MPV), a member of the genus Orthopoxvirus. MPV is a large, complex, double-stranded DNA virus of the chordopoxvirus family. MPV is endemic in central and western Africa and is a classic zoonosis acquired through contact with infected rodents and squirrels. Observational studies of human monkeypox in central and western Africa have revealed that MPV infection has an incubation period of 10-14 days and a period of infectivity during the first week of rash. MPV enters the body through skin abrasions, the upper respiratory tract mucosa, or by ingestion. During primary viremia, the virus migrates to regional lymph nodes and then disseminates throughout the body. Vaccination with vaccinia virus (smallpox vaccine) is highly protective (around 85%) against MPV infection. Post-exposure smallpox vaccination is indicated for persons who are at high risk of MPV infection, including those investigating animal or human monkeypox cases, health care workers caring for infected patients, and laboratory workers who handle specimens that may contain MPV.

Varicella-Zoster Immune Globulin

1. Michelle Hudspeth, MD 1. Johns Hopkins Hospital Baltimore, Md Varicella. American Academy of Pediatrics. In: Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2003:672– 686 Prevention of Varicella. Recommendations of the Advisory Committee on Immunization Practices. Centers for Disease Control and Prevention. Morbid Mortal Wkly Rep MMWR. 1996;45(No. RR-11) :1– 36[OpenUrl][1] Prevention of Varicella. Updated Recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention. Morbid Mortal Wkly Rep MMWR Recomm Rep. 1999;48(RR-6) :1– 5[OpenUrl][2] Varicella-zoster virus (VZV) is a highly contagious member of the herpesvirus family. It is spread when the virus comes into contact with conjunctiva or the mucosa of the upper respiratory tract. Routes of person-to-person transmission include direct contact with infected persons and aerosolized droplets from respiratory tract secretions. In addition, maternal varicella infection can lead to in utero infection through transplacental passage of the virus. The typical incubation period for varicella … [1]: {openurl}?query=rft.jtitle%253DMorbid%2BMortal%2BWkly%2BRep%2BMMWR.%26rft.volume%253D4511%26rft.spage%253D1%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: {openurl}?query=rft.jtitle%253DMorbid%2BMortal%2BWkly%2BRep%2BMMWR%2BRecomm%2BRep%26rft.volume%253D486%26rft.spage%253D1%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx

Diagnosis: Oral leishmaniasis

Diagnosis: Oral leishmaniasis

Deaths from accidental steam inhalation during traditional therapy

Death from accidental steam inhalation is quite a rare occurrence. Two cases of children who died during the inhalation of superheated steam in a closed room are reported. To our knowledge this is the first case report where children died from the injurious effects of steam while inhaling steam. At autopsy, petechial haemorrhages in brain, lungs, heart, and congestion of epiglottis, congestion and oedema of lungs were seen macroscopically. Microscopically, trachea showed swelling and oedema of mucosa and sub mucosa, focal loss of mucosal epithelium and coagulative necrosis with scanty inflammatory reaction, lungs showed congestion, oedema and haemorrhages. It is considered that these findings caused hypoxia and cause of death in these cases was accidental inhalation of superheated steam. It indicates that mucosa of respiratory tract is vulnerable to the effects of vapors of superheated steam. Moreover it would seem that fatal hypoxia occurs within a few minutes from the effects of inhalation of steam in a closed space.

Defense Mechanisms against Influenza Virus Infection in the Respiratory Tract Mucosa

Defense Mechanisms against Influenza Virus Infection in the Respiratory Tract Mucosa

Expansion of CCR5+ CD4+ T-lymphocytes in the course of active pulmonary tuberculosis.

Nonsyncytium inducing, macrophage tropic HIV strains predominate in the course of active tuberculosis (TB). The present study assesses the expression of CCR5 in CD4+ T-lymphocytes from blood and bronchoalveolar lavage (BAL) of TB patients, non-TB lung disease controls and healthy controls. Memory (CD45RO+), recently activated (CD69+), proliferating (Ki67+) CCR5+ or CCR3+ CD4+ T-lymphocytes were determined by multiparametric flow cytometry analysis. Results show that BAL CD4+ T-lymphocytes expressing CCR5 or CCR3 were significantly increased when compared to peripheral blood both in patients and in healthy controls. However, the data show that the proportions of peripheral blood CCR5+ CD4+ and CCR3+ CD4+ T-lymphocytes and BAL CCR5+ CD4+ T-lymphocytes, but not BAL CCR3+ CD4+ T-lymphocytes, were significantly increased in TB patients. Furthermore, the observation that BAL CCR5+ CD4+ T-lymphocytes from TB patients expressed early activation markers, were not proliferating and showed down-regulation of CCR5 expression suggests recruitment and trapping at the site of disease. Altogether, these results suggest that the lower respiratory tract mucosa may provide cellular targets accessible for efficient transmission of macrophage tropic HIV-1 variants and that tuberculosis may enhance this phenomenon.

Immunohistochemical demonstration of carbonic anhydrase isoenzyme VI (CA VI) expression in rat lower airways and lung.

Carbonic anhydrase isoenzyme VI (CA VI), which is transported in high concentrations in saliva and milk into the alimentary tract, is an important element of mucosal protection in the upper alimentary tract. Like alimentary tract mucosa, the respiratory tract mucosa is also exposed to heavy microbial, physical, and chemical stress. The protective and renewal-promoting factors present in the surface mucus of the respiratory tract are mainly produced by the seromucous tracheobronchial glands. Here we studied the secretion of CA VI by these glands in adult and developing rats using immunohistochemical techniques. The serous acinar and duct cells of the tracheobronchial glands stained for CA VI. The presence of the enzyme also in the duct content indicates its active secretion into the surface mucus. CA VI was also visible in the secretory cells and at the base of the ciliated cells of the tracheobronchial surface epithelium. Moreover, the Clara cells of the bronchiolar surface epithelium stained for CA VI. These findings are consistent with the hypothesis that CA VI has a mucosa-protective role not only in the gastrointestinal tract but also in the respiratory tract, where CA VI may act as a pivotal pH neutralizer and growth factor.

Rhinopharyngites de l’enfant

The “common cold” or upper respiratory tract infection (URI) is a moderate inflammation of the upper respiratory tract mucosa extended from the nasal cavity to the larynx. The main symptoms are nasal obstruction, rhinorrhea, pharyngeal pain, sneezing, and coughing. Acute URI is a viral infection. It usually heals without any complication, and does not require any bacteriological samples nor antibiotherapy. First-line treatment consists of analgesic and antipyretic drugs associated with normal or hypertonic saline nasal wash. The most frequent URI complications are infectious diseases, mainly otitis media, sinusitis, and upper airway obstruction. URI recurrences that are often observed after the age of 6 months reflect a physiological process of maturation of the immune system. If the frequency of recurrences becomes overwhelming, some risk factors, such as passive smoking and day care attendance, must be searched for and, if possible, suppressed. Adenoidectomy is not indicated in the absence of complications. Ongoing clinical and experimental researches are carried out in order to develop new antiviral drugs aimed at preventing or healing URI.

Review of Newcastle disease virus with particular references to immunity and vaccination

Newcastle disease (ND) is a highly contagious disease. The present paper deals with classification of ND virus (NDV), clinical signs and pathology, virus strain classification and molecular backgrounds for the pathogenicity. Major emphasis is reviewing immunity and vaccination. Clinical forms of the disease vary depending on many factors, but mainly on the virulence of Newcastle disease virus (NDV) strains. Virulent strains are considered List A pathogens by the ‘Office International des Epizooties' (OIE). The virulence has been traditionally determined using in vivo pathogenicity tests to distinguish between highly, moderately and low virulent isolates. More recently, molecular biological techniques like polymerase chain reaction and sequencing have been described to differentiate virulent from non-virulent strains.The systemic and mucosal immune systems are considered to function more or less independently. Systemic antibodies are essential elements in protection against ND, whereas the local antibodies limit multiplication of NDV at the site of entry. Cytotoxic T lymphocytes specific against NDV have been detected in the spleen of vaccinated birds, however, their contribution to protection remains to be elucidated. An increase of the number of various leukocyte subsets was noticed in the respiratory tract and the Harderian gland (HG), which favours involvement of local cellular immunity in the defence against NDV infection. It is tempting to speculate that the local lymphoid infiltrates are involved in first defence and that cytolytic cells clear virus by directly lysing infected target cells at the site of NDV inoculation. Secondly, various cell types, mainly T-lymphocytes and macrophages, may be equipped to produce a range of cytokines with antiviral activity and cytokines that stimulate B-lymphocytes to proliferate and differentiate into antibody-forming cells responsible for the local antibody production against NDV.Vaccination using inactivated virus induces mainly systemic immunity and usually protects birds from disease caused by virulent NDV strains. Mucosal vaccination would be more attractive, as it induces in addition to systemic immunity a local IgM, IgA, and IgG, response as well as a mucosal cellular immune response. These local responses contribute to protection against NDV infection of the respiratory tract mucosa, which is the first target tissue of infection with this virus.

Antibiotics for persistent nasal discharge (rhinosinusitis) in children.

Nasal discharge (rhinosinusitis) is the result of inflammation of the mucosa of the upper respiratory tract, and is usually due to either infection or allergy. To determine the effectiveness of antibiotics versus placebo or standard therapy in treating children with persistent nasal discharge (>10 days). The Cochrane Controlled Trials Register, MEDLINE, EMBASE, and bibliographies of relevant articles were searched. Authors and pharmaceutical companies were contacted. Date of most recent searches: March 2000. All randomized controlled trials that compared antibiotics versus placebo or standard therapy (decongestants or nasal saline drops). Trials which included the use of other medications were included if all participants were allowed equal access to such medications or if the additional or alternative therapies were regarded as ineffective. Trials that only combined or compared antibiotics with surgery, or sinus puncture and lavage, were not included in the review. Data were extracted by a single reviewer for the following outcomes: clinical failure, failure to improve, clinical improvement, time to resolution, complications, side-effects and bacteriologic failure. For the dichotomous outcome variables of each individual study, proportional and absolute risk reductions were calculated using a modified intention-to-treat analysis. The summary weighted risk ratio and 95% confidence interval (fixed effects model) were calculated using the inverse of the variance of each study result for weighting (Cochrane statistical package, REVMAN version 4.3). A total of five studies involving 401 children compared antibiotics with placebo or standard therapy. Only one of the seven outcomes (clinical failure) was reported in all studies. Around 45% of children did not have a clinical success documented when reviewed 2-6 weeks after randomization. The control event rate varied from to 47-71% (mean 56%). The risk ratio estimated using a fixed effects model was 0.72 (95% CI 0.59, 0.89). The estimated effect size was consistent in four of the five studies. For children with persistent nasal discharge or older children with radiographically confirmed sinusitis, the available evidence suggests that antibiotics given for 10 days will reduce the probability of persistence in the short to medium-term. The benefits appear to be modest and around six children must be treated in order to achieve one additional cure. No long term benefits have been documented. These conclusions are based on a small number of small randomized controlled trials and additional larger well-designed studies are indicated.

The search for a strangles vaccine

The search for a strangles vaccine

The Haemophilus influenzae Hap autotransporter binds to fibronectin, laminin, and collagen IV.

Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the upper respiratory tract mucosa. NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane. In this study, we examined interactions between the H. influenzae Hap adhesin and selected extracellular matrix proteins. Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Hap(s), from the bacterial cell surface. We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Hap(s). Purified Hap(s) binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II. Binding of Hap(s) to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract.

Résistance aux antibiotiques : le modèle bêta-lactamines est-il transposable aux fluoroquinolones ?

The spread and worldwide increasing prevalence of beta-lactam resistance in S. pneumoniae (42 % in France) are related to two specific features of this pathogen, its natural capacity to colonize the upper respiratory tract mucosa and its natural competence for transformation, e.g., by the viridans group streptococci which represent a resistance gene reservoir. The epidemiological evolution of beta-lactam resistance in S. pneumoniae provides a good model from which to extrapolate on the emergence of fluoroquinolone resistance although there are differences in the prevalence of the mechanisms that lead to resistance. Fluoroquinolone resistance (ca. 1 %) is mainly due to either target modifications by point mutations in topoisomerase IV or gyrase, or to increased active efflux. Horizontal gene transfer appears to be less frequently involved in the acquisition of fluoroquinolone resistance than of beta-lactam resistance where it is the main mechanism leading to resistance via the formation of mosaic penicillin binding proteins with reduced affinity for beta-lactam antibiotics. The prevalence of both fluoroquinolone resistance and horizontal gene transfer has been considered to be greater among viridans group streptococci than pneumococci. This could be the consequence of the use of older quinolones with poor activity against pneumococci and streptococci, with a selective pressure exerted mainly against viridans group streptococci since quinolones are quasi-exclusively used in adults. The knowledge of the molecular bases of fluoroquinolone resistance should allow a more rational use of these molecules in order to preserve their efficacy, and an efficient epidemiological surveillance to help predict the evolution of this resistance.

High prevalence of influenza specific antibody secreting cells in nasal mucosa.

Secretory immunoglobulin A (SIgA) provides the first line of defence against pathogens initiating infection via the mucosal route, e.g. the influenza virus. The aim of this study was to examine the basal level of influenza-specific antibody-secreting cell (ASC) in the local mucosa of the upper respiratory tract. Nineteen patients scheduled for tonsillectomy were enrolled for the study, and they had not experienced influenza during the previous year. Tonsils, blood, oral fluid and a nasal biopsy were sampled, and the basal levels of ASC and antibodies (Abs) were determined. We found low numbers of influenza-specific ASC in the blood and tonsils, but there were about 10-100 times higher numbers of specific ASC in the nasal mucosa tissue despite no recent influenza exposure. Thus, the basal level of influenza-specific ASC in the mucosa of the respiratory tract may be important in the protection against influenza infection.

Development of an ex vivo model to study adherence of Mannheimia haemolytica serovar 1 to mucosal tissues of the respiratory tract of cattle.

To develop and validate an ex vivo model for study of adherence of Mannheimia haemolytica (formerly Pasteurella haemolytica) to respiratory tract mucosa of cattle and to use this model to confirm adherence of M haemolytica serovar 1 (Mh1) to several relevant respiratory mucosal surfaces. Excised nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue from the bovine upper respiratory tract. Mh1 was radiolabeled by use of tritiated leucine. Various concentrations of labeled bacteria were incubated with bovine upper respiratory tract tissues for various times. Tissue was washed to remove nonadherent bacteria, and percentage of bacteria adhered (percentage of adherence) was estimated using radioactivity. Using an optimal inoculum concentration and incubation time, percentage of Mh1 adherence was compared on nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue, and adherence to nasopharyngeal tissue was confirmed by scanning and transmission electron microscopy. The optimal Mh1 inoculum concentration was 1 X 10(7) colony forming units/ml and incubation time was 3 hours. Percentage of adherence of Mh1 to nasopharyngeal tissue was greater than adherence to other tissue types. The ex vivo model maintained the functional and structural integrity of bovine upper respiratory tract mucosa, as confirmed by light and electron microscopy. Electron microscopy revealed participation of epithelial cell cilia and surface mucus in adherence of Mh1 to nasopharyngeal tissue. Adherence of Mh1 was confirmed in repeated assays, indicating that this organism adheres to upper respiratory tract mucosa of cattle.

2. Mucosal leishmaniasis

Sudanese mucosal leishmaniasis is a chronic infection of the upper respiratory tract and/or oral mucosa caused mainly by Leishmania donovani. The disease occurs in areas of the country endemic for visceral leishmaniasis, particularly among Masalit and other closely related tribes in western Sudan. The condition may develop during or after an attack of visceral leishmaniasis, but in most cases it is a primary mucosal disease. Unlike South American mucocutaneous leishmaniasis, mucosal leishmaniasis in Sudan is not preceded or accompanied by a cutaneous lesion. Pathologically, the lesions show a mixture of macrophages, plasma cells and lymphocytes. An epithelioid granuloma may also be found. Parasites are scanty. Diagnosis is established by demonstration of parasites in smears or biopsies, by culture or animal inoculation, or with the aid of the polymerase chain reaction. Most patients give positive results in the direct agglutination test and leishmanin skin test. Patients respond well to treatment with pentavalent antimony compounds.

Optimal technique to diagnose primary ciliary dyskinesia.

To develop a cost-effective protocol for diagnosing primary ciliary dyskinesia (PCD). Retrospective chart review in a tertiary care academic medical center. A review of the electron microscopy logbook identified all patients who had a suspected diagnosis of PCD. Biopsy of respiratory tract mucosa was performed using a cytology brush or a cup forceps in the outpatient clinic or operating room (OR). Outcome measures were to determine the diagnostic adequacy of cytological evaluation compared with tissue biopsy and to determine whether an adequate nasal mucosa sample can be collected in the outpatient clinic setting as compared with the OR and the use of general anesthesia Twenty-seven patients underwent 31 biopsies. Fifteen specimens were collected with a cup forceps, and 16 with a cytology brush. The sampling sites were nasal mucosa in 28 cases and trachea in the rest. Twelve specimens (39%) were collected in the clinic; the rest were obtained in the OR in conjunction with another procedure. Neither method of specimen collection nor mode of anesthesia made a significant difference in the probability of obtaining an adequate specimen. Ten samples were nondiagnostic: cytological evaluation, 31% (n = 16); tissue biopsy, 27% (n = 15); clinic, 42% (n = 12); and OR, 31% (n = 16). The cost of evaluating ciliary motion at our institution was $150, with an additional charge of $1,297 for electron microscopic evaluation. The nonprofessional fee for an outpatient nasal biopsy was $98; in the OR the cost of anesthesia supplies, surgical suite, recovery room, and day-surgery bed was at least $1,860. Our results suggest that the optimal method for diagnosis of PCD is in the outpatient clinic with specimen collection by means of either a cup forceps or a cytology brush.

The nose versus the environment: 1982 and today.

A brief overview of recent publications dealing with the effects of environmental pollutants on upper respiratory tract mucosa is presented. It mainly focuses on airborne irritants, substances inducing epithelial hyperplasia, metaplasia, and epithelial damage, and on inflammatory changes of nasal mucosa associated with environmental pollutants. Data from epidemiologic surveys, human exposure studies, animal experiments, and in vitro studies have improved present concepts of the significance of environmental pollutants for upper respiratory diseases. Although various national and international initiatives have resulted in a considerable reduction of indoor and outdoor pollutants within recent years, environmental pollutants continue to affect upper respiratory tract health of the population in urban areas and industrialized regions. Continuing efforts to reduce emissions of air pollutants are indispensable.

Haemophilus influenzae in chronic bronchitis.

Colonization of the adult respiratory tract with nontypable Haemophilus influenzae is a dynamic process with new strains being acquired and replacing old strains periodically. The organism is a common cause of exacerbations of chronic bronchitis based on 3 lines of evidence: quantitative culture of the lower airways obtained by protected specimen brush, antibiotic trials, and serological studies. Nontypable H. influenzae expresses multiple adhesin molecules that mediate adherence to the respiratory tract mucosa. Recent studies have established that the bacterium penetrates the mucosal surface and survives intracellularly and in the interstitium of the submucosa. The organism shows a remarkable degree of antigenic diversity on its surface, including phase variation of lipooligosaccharide, antigenic heterogeneity of surface proteins, point mutations in genes encoding surface proteins and horizontal transfer of genes. These strategies facilitate evasion of the human immune response. Substantial progress has been made in identifying vaccine antigens to prevent infections caused by nontypable H. influenzae.

Nasal obstruction: an alternative to ostiomeatal complex dysfunction in sinus disease.

Ostial patency is thought to be essential to the function of the maxillary sinus. Ostiomeatal complex dysfunction has been implicated as a major factor in the pathogenesis of sinus disease. However, recent work in our laboratory has indicated that other factors may also contribute to this process. The objective of this study was to determine the effect of nasal obstruction in maxillary sinus gas composition, independent of its effect on ostial ventilation. Prospective controlled animal study. Independent models of nasal obstruction and ostial occlusion in contralateral sinuses were established. Ipsilateral models of nasal obstruction and ostial occlusion were also created. Gas samples from each of the manipulated sinuses were analyzed on a gas chromatogram and compared. Results revealed a dramatic and highly significant increase in antral carbon dioxide (CO2) concentrations in the sinuses ipsilateral to either an occluded ostium or an obstructed nostril, compared with the controls. These effects on CO2 concentrations were additive when ipsilateral nasal obstruction and ostial occlusion were created. Furthermore, the effect of nasal obstruction in modulation of antral CO2 levels was found to be beyond its effect on hypoventilation of the sinus and to be independent of ostial functional status. We have established independent models of nasal obstruction and ostial occlusion in the same animal. Our findings suggest that ostiomeatal complex dysfunction might not be the sole underlying factor in the pathogenesis of sinus disease in all individuals. Integrity of nasal airflow seems to have a significant effect on the maintenance of the aerobic antral environment, essential to the maintenance of normal sinus function. Modulation of maxillary sinus gas composition by nasal airflow, independent of ostial patency, may be explained by the possible presence of flow-sensitive receptors in the upper respiratory tract mucosa. Work to identify such receptors is currently in progress.