Primary Tuberculous Infection Research Articles

Eitt sindur um tuberklasmittuna

This paper is part of a treatise dealing with the clinical features of primary tuberculous infection, and the purpose of the present work is to contribute to the clinic of primary tuberculosis. Some literature about the theme is surveyed. The material used has been collected at the Tuberculosis Station of the Faroe Islands at Hoydal during the author's time of service there from 1939 to 1947. An account is given of the working plan of this tuberculosis station, where besides ordinary station work special attention is paid to the tuberculin register. The tuberculin reaction used has been Pirquet 's test. The material comprises a total of 430 cases of initial fever. The fever curve for adults was typically continual, while with children it vas irregular; the duration of the fever was similar for children and adults, generally 2 or 3 weeks; in l/4 of the cases it lasted more than one month. Maximum temperature generally about 39 degrees C might, however, be higher, especially with children. The duration and height of the fever had no prognostic significance. Slow pulse was a constant symptom witli adults, but was seldom noticed with children. This relative bradycardiagenerally lasted till the middle of ihe fever period. Krythema nodosum was a frequent symptom ot' initial fever and occurred 76 times among the 430 cases of initial fever. Sedimentation rate practically always increased, as a rule moderately, and decreased as the fever fell, but more slowly. X-rays examinations have been made during initial fever in 146 cases. X-rays changes were stated in all the children and in more than % of the adults. The changes stated were chifly enlarged hilar shadows, some had also infiltrations. Rather more than *4 had subjective symptoms, a number which is undoubtedly too low. The most frequent symptoms where retrosternal pain and soreness of the lower end of sternum, a stitch in the side, and pain between the shoulderblades. The mentioned symptoms must be supposed to bi' caused by tlie pathologic anatomic changes.

EVALUATION OF SPECIFIC ANTIGENS AT THE EARLY STAGE OF TUBERCULOUS INFECTION IN CHILDREN

More specific antigens are still being searched for in order to increase informativeness of techniques for early diagnostics of tuberculous infection. Aimed at the investigation of proteins of tuberculous mycobacteria (PPD-L, ESAT 6, 85, hybrid of ЕSAT 6 CFP 10, CFP32B, Rv2660c) the study was conducted including testing of induced IFN-γ in the children ill with tuberculosis in the early period of primary tuberculous infection and also those not infected with tuberculous mycobacteria – 130 children in the age from 6.0 ± 0.4 years old. It was found out that tuberculin remained to be valuable for evaluation of the intensity of anti-tuberculosis immunity. Antigens of ESAT 6, 85, CFP32B, Rv2660c were identified as proteins of the early stage of tuberculous infection. The presence of response when stimulating by the above antigens was typical of the favorable course of tuberculosis. Antigens of ESAT 6 and Rv2660c were valuable for assessment of latent tuberculous infections and the hybrid of ЕSAT 6 CFP 10 – for diagnostics of tuberculosis. Therefore introduction of immunological tests (in vitro) into the set of diagnostic tools allows optimizing the early diagnostics of tuberculous infection in children and forecasting the course of the disease when tuberculosis has developed.

ОСОБЕННОСТИ ТУБЕРКУЛЕЗА У РЕБЕНКА С СОПУТСТВУЮЩЕЙ ПАТАЛОГИЕЙ

The clinical case demonstrated the intermittent course of primary tuberculosis caused by multiple drug resistant mycobacteria in 8 year old child with concurrent disorders of CNS and locomotor apparatus and living in the social institution of the closed type. The disease was detected in 2 years after the early period of primary tuberculous infection and administered preventive treatment by two anti-tuberculosis drugs. The disease was diagnosed during examination due to aspiration pneumonia with expressed clinical manifestations. Treatment of aspiration pneumonia and multiple drug resistant pulmonary tuberculosis was successfully completed.

Mycobacterium Tuberculosis Infection of the Placenta: A Study of the Early (Innate) Inflammatory Response in Two Cases

Infections with Mycobacterium tuberculosis (MTb) are globally prevalent in many countries, yet descriptions of placental pathology in tuberculous patients are scanty. The usual necrotizing granulomatous response associated with tuberculous infections requires an activation of the adaptive immune system. However, before this system is turned on, the 1st encounter with the tubercle bacillus is mediated by the innate immune system. This pathway utilizes innate surface receptors in neutrophils and histiocytes predominantly and does not produce a granulomatous pattern of inflammation. In this report we describe 2 cases of placental involvement with MTb in which an acute abscess-like inflammatory response with Myeloperoxidase and CD68-positive neutrophils and histiocytes causing acute villitis and intervillitis, with abundant acid-fast mycobacteria, were identified. Other cellular markers consistent with adaptive immunity were negative. These nongranulomatous lesions are seen in primary tuberculous infections occurring in a naïve woman and, obviously, a naïve fetus. These cases with early response inflammation in the placenta are frequently missed precisely because the mother is not known to be infected or has been recently diagnosed and because the symptoms in the newborn may not develop for several weeks, by which time the placenta may have been discarded. This report also shows that the differential diagnosis of acute villitis and intervillitis in the placenta should include tuberculosis aside from the more common bacterial infections such as listeriosis.

Tuberculous Pericarditis

Tuberculous pericarditis, caused by Mycobacterium Tuberculosis, is found in approximately 1% of all autopsied cases of tuberculosis (TB) and in 1% to 2% of instances of pulmonary TB.1 Pericardial involvement usually develops by the retrograde lymphatic spread of Mycobacterium Tuberculosis from peritrachial, peribronchial or mediastinal lymph nodes or by hematogenous spread from primary tuberculous infection.2, 3 Tuberculous pericarditis presents clinically in 3 forms, consisting of pericardial effusion, constrictive pericarditis and a combination of effusion and constriction.4

Surgical site infection by Mycobacterium tuberculosis following caesarian section

Surgical site infection by M. tuberculosis is uncommon and its diagnosis can be missed unless there is strong clinical suspicion coupled with laboratory confirmation. We report a case of primary tuberculous surgical site infection without any evidence of pulmonary, skeletal or gastrointestinal tuberculosis in an immunocompetent patient, presented as non healing discharging wound following lower uterine caesarean section (LUCS). This is the first case report of its kind from Bangladesh to the best of our knowledge. The case was diagnosed by detection of acid fast bacilli (AFB) in pus by Ziehl Neelsen staining and histological evidence of granulomatous lesion compatible with tuberculosis found in surgically excised granulation tissue. The patient was treated with 4 anti-tubercular drugs regimen for initial two months and responded well showing complete healing of her wound. The case is being reported primarily for its unusual site and rarity as Mycobacterial infection.

Primary tuberculous infection of breast: experiences of surgical resection for aged patients and review of literature

Primary mammary tuberculosis is a rare entity that usually occurs in female of reproductive age. Herein three such patients including two males with ages over 80 years, who underwent surgical resection, are reported. Fine needle biopsy failed to achieve specific diagnosis before surgical operation. All of their conditions got satisfactory improvement and anti-tuberculosis chemotherapy was administered postoperatively. Previous literature related to the epidemiology, diagnosis and treatment for mammary tuberculosis will be also reviewed. Mammary tuberculosis is usually related to breast feeding women and is extremely rare in aged man. The possible mechanisms resulting in this disease in our three patients, including direct extension, reactivation, or transmitted by staffs or peers of the nursing home, would also be discussed.

Tuberculous infection of the elbow joint

Tuberculosis remains a major health problem worldwide with musculoskeletal involvement reported to be infrequent. A resurgence of pulmonary tuberculosis is being evidenced, especially along with the increasing incidence of immunocompromised states and with this a concomitant rise in musculoskeletal tuberculosis. Unusual presentations of tubercular arthritis and equivocal investigations along with clinician inexperience can result in delay in diagnosis. The morbidity of delayed or untreated tubercular arthritis can be devastating, ending in painful ankylosis or a requirement for salvage procedures like excisional arthroplasty or arthrodesis. The early diagnosis of osteoarticular tuberculosis can be difficult. Presentation of the disease can mimic other conditions like neoplasia, non-tubercular infections and inflammatory arthropathy. Reports of tuberculous infection of the elbow are few. We report a case of a primary tuberculous infection of the elbow joint that presented as an isolated abscess in the cubital fossa, without pulmonary or systemic involvement. To prevent considerable morbidity, a diagnosis of tuberculosis should be included in the repertoire of diagnostic possibilities when confronted with unusual musculoskeletal manifestations.

Increase of tuberculous infection in the organs of B cell-deficient mice.

Protective immunity against infection with Mycobacterium tuberculosis is imparted by T cells rather than antibodies, but B cells can play a role as antigen-presenting cells and in granuloma formation. We re-evaluated the role of B cells in the course of tuberculous infection in mu-chain knock-out (Ig-) mice. Surprisingly, the organs of M. tuberculosis-infected Ig- mice were found to have three- to eight-fold elevated counts of viable bacilli compared with normal littermates at 3-6 weeks post-infection. Splenic interferon-gamma responses to whole antigen were unimpaired, whilst proliferation to certain mycobacterial peptides was found to be diminished. However, bacille Calmette-Guérin (BCG) vaccination significantly reduced the infection in Ig- mice. The mechanisms by which B cells can influence primary tuberculous infection need further study.

Contribution of the polymerase chain reaction to the diagnosis of tuberculous infections in children.

The purpose of the study was to evaluate the contribution of polymerase chain reaction (PCR) to the diagnosis of tuberculous infection in children. Two different PCR techniques were compared to the standard bacteriological methods for the detection of Mycobacterium tuberculosis in 157 specimens obtained from the respiratory system of 51 children. Patients were classified in three groups: 12 patients with active disease (57 specimens), 12 patients with silent tuberculous infection (23 specimens) and 27 patients without tuberculosis (77 specimens). One PCR method (PCR/Ag85) used amplification of a fragment of the genes coding for the mycobacterial antigen 85 followed by hybridization of a probe specific for M. tuberculosis on the Southern blot of amplified DNA. The other PCR technique was a nested PCR (NPCR) using double amplification of a fragment of the insertion element IS6110 only present in the M. tuberculosis genome. The sensitivities of the different techniques, compared to the clinical diagnosis, were 7.0% for acid fast staining, 22.8% for culture, 24.6% for PCR/Ag85 and 44.9% for NPCR in active disease, 4.3% for culture, 8.7% for PCR/Ag85 and 28.6% for NPCR in silent tuberculous infection. The specificities were 100% for culture, 94.8% for PCR/Ag85 and 87.9% for NPCR. Among the 12 children clinically considered as having active tuberculosis, 1 had smear positive samples, 4 had at least one positive culture, 7 at least one positive PCR/Ag85 and 9 at least one NPCR positive sample. Among the 12 children having silent tuberculous infection, none had positive smears, 1 had one positive culture, 2 had at least one positive PCR/Ag85 and 5 at least one NPCR positive sample. Our study suggests that both PCR techniques, and especially NPCR, are able to detect M. tuberculosis DNA in specimens containing few micro-organisms. PCR methods are more sensitive than culture and the results are available more quickly. Testing multiple samples from the same individual increased the sensitivity. In view of occasional false-positive results, cultures remain the gold standard to establish definitive diagnosis of primary tuberculous infection in children.

Mycobacterium tuberculosis in lung transplant recipients.

The diagnosis and treatment of Mycobacterium tuberculosis, although difficult in normal hosts, are even more complex in transplant recipients. As a result of the use of immunosuppressive agents, transplant recipients are not only predisposed to primary tuberculous infections, but they are also uniquely at risk for reactivation of latent infection acquired prior to transplantation or transmitted via the donor organ. The diagnosis of pulmonary tuberculosis can be even more elusive in the setting of lung transplantation where other pulmonary complications can make diagnosis difficult. Here we report a case of a patient who died of disseminated M. tuberculosis 12 wk after lung transplantation, and we review tuberculous infections in lung transplant recipients.

Adult-onset pulmonary tuberculosis: findings on chest radiographs and CT scans.

Adult-onset pulmonary tuberculosis refers to primary tuberculous infection occurring initially in adults. The decreasing exposure in childhood, owing to careful public health measures and the advent of antituberculous chemotherapy, has resulted in later initial exposure to tuberculosis and an increased likelihood of susceptibility to tuberculosis during adulthood [1-3]. In addition, chest radiographs typically show a pattern more consistent with primary infection in pulmonary tuberculosis associated with AIDS. In this essay, we illustrate the spectrum of radiographic and CT findings of adult-onset pulmonary tuberculosis in patients without AIDS.

Primary tuberculous chancre in a renal transplant patient

A case of primary tuberculous chancre of the vulva is reported. Although a tuberculous infection in an immunocompromised patient is not uncommon, this is the first report of a primary tuberculous infection on the external genitalia in such a patient. The source of infection in this patient could not be determined.

Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: Development of a new concept

The humoral immune response occurring during mycobacterial infections was analysed with an ELISA test based on antigen 60. With tuberculosis, IgM antibodies indicate a primo-infection or a process of reactivation while IgG determinations allow an evaluation of the intensity of the infectious process. The test is also applicable to extrapulmonary tuberculosis, provided its sensitivity be adapted to these particular cases. This is particularly clear for tuberculous meningitis. The test is not species-specific and allows the detection of antibodies in atypical mycobacterioses and in leprosy patients. The final differentiation must be done by clinical examinations and cultures. In leprosy patients, IgM antibodies are detected nearly as frequently as IgG antibodies. In HIV-seropositive patients, the A60 seropositivity is correlated with a reactivation of former tuberculous infections and with primary tuberculous infections. At the AIDS stage, the A-60 seropositivity is due to atypical mycobacteria, with a better IgM than IgG response. Healthy people are negative in serology: the positive cases observed are due to inapparent infections gained by contact with an infectious focus. The seropositive cases observed in non-tuberculous hospitalized patients are restricted to some disease types, essentially lung infections (cystic fibrosis, cancer pneumopathies, sarcoidosis). Some patients have low levels of antibodies. This anergy may be traced to the formation of immune complexes or else to a weak avidity of the specific antibodies produced. This test should not be considered to be a diagnostic tool by itself. It should be used in conjunction with other diagnostic means that, together, allow the determination of a diagnosis.

Absence of IgG or IgM Antibody Response to Mycobacterium tuberculosis 30,OOO-Da Antigen after Primary Tuberculous Infection

Absence of IgG or IgM Antibody Response to Mycobacterium tuberculosis 30,OOO-Da Antigen after Primary Tuberculous Infection

Tuberculous Pleural Effusions: Evidence for Selective Presence of PPD-Specific T-Lymphocytes at Site of Inflammation in the Early Phase of the Infection

Patients with tuberculous pleural effusions may show cutaneous anergy to tuberculin purified-protein derivative (PPD). This phenomenon has been attributed either to preferential sequestration of antigen-specific T-lymphocytes to the pleural space or to the presence of suppressor monocytes in the blood. In 2 patients with primary tuberculous infection involving the pleura and with skin anergy to PPD, the in vitro proliferation of pleural and peripheral blood T-cells to PPD was evaluated. Although peripheral blood T-cells were not reactive, pleural T-cells showed a marked proliferative response to PPD. At least in the first patient, the lack of proliferation of circulating T-cells could not be related to the presence of suppressor monocytes. Interestingly, after 4 to 8 wk of specific chemotherapy, PPD skin test became positive and the blood T-lymphocytes responded in vitro to the same antigen. Pleural T-lymphocytes were used to generate long-term, PPD-specific T-cell lines and could be maintained in vitro for more than 3 months with repeated cycles of stimulation. The pleural and the blood T-lymphocytes and the T-cell lines were also characterized phenotypically: although the majority of the T-lymphocytes present in the pleural space after Mycobacterium tuberculosis infection were Leu-3-positive (helper T-cells), T-cell lines proliferating in response to PPD included high numbers of Leu-2-positive cells (suppressor/cytotoxic T-cells). These data suggest that early skin anergy in tuberculous pleurisy may be associated with sequestration of PPD-reactive T-lymphocytes in the pleural spaces involving both Leu-2-and Leu-3-positive T-cells.

Tuberculous meningitis in an urban medical center.

Forty-five cases of tuberculous meningitis at a large urban medical center were reviewed. Reasons for the continued incidence, prognostic factors, and current therapy of this life-threatening form of tuberculosis were examined. Thirty-nine of 45 patients were black, Hispanic, and/or 65 years of age or older (87%). Underlying conditions included alcohol abuse in 12, intravenous drug abuse in 7, recent steroid therapy in 4, head trauma in 4, recent pregnancy in 4, and the acquired immunodeficiency syndrome in 1. Thirty-four patients (76%) presented with altered mental status and/or focal neurologic findings. Significant mortality (31%) occurred despite the administration of antituberculous therapy to all but 1 patient. Six of 14 deaths (43%) occurred in the first week of hospitalization. One-third of survivors had neurologic sequelae at the time of follow-up. Neurologic deficits on admission, advanced age, and alcohol abuse were frequent among those who succumbed. Early recognition and treatment in hospital failed to improve outcome in advanced cases. From these findings we conclude that both aggressive treatment of primary tuberculous infections as well as prevention of secondary cases are necessary to effect any further reduction in the incidence, morbidity, and mortality of tuberculous meningitis.

Tuberculosis and the anterior optic pathways

Sixteen patients (one with tuberculoma of the anterior optic pathways, the other 15 with opto-chiasmatic arachnoiditis) are presented. They are divided into three categories (definite, likely, possible) from the point of view of the pathogenetic link of their optic pathology with a primary tuberculous infection. Neurosurgical treatment had a positive effect upon the visual symptoms in five patients (31.25%), no effect in three cases (18.75%); in the other eight patients (50%) it could not prevent progression of visual impairment.

Tuberculous mediastinal lymphadenopathy in Bradford

During the calendar year 1978, 18 patients who commenced treatment for pulmonary tuberculosis in the Bradford Chest Clinic were found to have enlarged mediastinal lymph glands. Sixteen of these 18 patients were adults who thus presented radiographic patterns which have been classically regarded are representing primary tuberculous infection and are usually seen in children but only rarely in adults. All 16 adult patients were immigrants of either Indian or Pakistani origin. Tuberculosis is therefore a common cause of mediastinal lymphadenopathy in the immigrant population and in view of the successful response to therapy it should be considered ahead of the more usual diagnoses of lymphoma, sarcoidosis or metastatic carcinoma.

Simple Primary Tuberculosis in an Elderly Woman

The diagnosis of primary tuberculous infection was made in a 78-year-old woman. The chest roentgenographic findings were remarkably similar to those often seen in children and adolescents with primary infection. Like the majority of adults with this entity, the patient was asymptomatic; the diagnosis was suspected epidemiologically and was confirmed by culture of M. tuberculosis from the sputum. As the incidence of new tuberculosis cases declines, the diagnosis of primary tuberculosis in the adult may be made more frequently.