Different Clinical Forms Of Tuberculosis Research Articles

Clinical course of respiratory tuberculosis relapses in the Kazakh population depending on HLA-DRB1 gene alleles.

The study aimed to ascertain the prevalence and frequency of relapses of respiratory tuberculosis (TB) and examine the characteristics of its clinical progression in members of the Kazakh population based on the alleles of the HLA-DRB1 gene. Methods of clinical and genetic research, statistical processing and analysis of the obtained data were used to achieve this goal. The research led to an analysis of the statistical processing of clinical and genetic investigations that found out how often TB in the respiratory tract is found and how different HLA-DRB1 gene alleles affect the disease's progression. To find out how exposure to certain HLA-DRB1 gene alleles affects the chance of relapse, the number of times they were found was compared between people who had relapsed and people who had just been diagnosed with TB. The impact of these alleles on the progression of the disease was assessed based on their frequency of detection of different clinical forms of TB (infiltrative, fibro-cavernous, generalised, disseminated), unilateral and bilateral lung damage, lung tissue deterioration, and the presence of bacterial secretions. The highest detection rate for all comparisons had gene alleles HLA-DRB1*01 (9.5%), *08 (4.2%), *15 (3.9%), *09 (1.6%), *12 (1.3%), *13 (0.9%), *11 (0.2%). The study found that Kazakhs with the HLA-DRB1*01, *08, and 15 gene alleles are more likely to develop recurrent respiratory TB. The study's practical value lies in its potential to utilise its findings for the prompt identification and eradication of genetic variables contributing to the recurrence of TB.

Epidemiological and Cytokine Profile of Patients with Pulmonary and Extrapulmonary Tuberculosis in a Population of the Brazilian Amazon.

Several factors are associated with the development of different clinical forms of tuberculosis (TB). The present study evaluated epidemiological variables and cytokine levels in samples from 89 patients with TB (75 with pulmonary TB and 14 with extrapulmonary TB) and 45 controls. Cytokines were measured by flow cytometry (Human Th1/Th2/Th17 Cytometric Bead Array kit). The TB group had a higher frequency of individuals who were 39 years of age or older, married, with primary education or illiterate and had a lower family income (p < 0.05). All individuals with extrapulmonary TB reported that they were not working, and the main reasons were related to disease symptoms or treatment. The levels of IFN-γ (OR = 4.06) and IL-4 (OR = 2.62) were more likely to be elevated in the TB group (p = 0.05), and IFN-γ levels were lower in patients with extrapulmonary TB compared to those with pulmonary TB (OR = 0.11; p = 0.0050). The ROC curve was applied to investigate the diagnostic accuracy of IFN-γ levels between the different clinical forms of tuberculosis, resulting in high AUC (0.8661; p < 0.0001), sensitivity (93.85%) and specificity median (65.90%), suggesting that IFN-γ levels are useful to differentiate pulmonary TB from extrapulmonary TB. The dysregulation of pro- and anti-inflammatory cytokine levels represent a risk for the development of TB and contribute to the pathogenesis of the disease, especially variation in IFN-γ levels, which may determine protection or risk for extrapulmonary TB.

CD4+ regulatory T cells and CD4+ activated T cells in new active and relapse tuberculosis

The aim of the present study was to examine characteristics of tuberculosis (TB) patients with different clinical forms and to study the frequency of Regulatory T cells (Treg cells) and Activated T cells in patients with new active and relapse TB. Forty-five pulmonary TB patients and a control group of 15 healthy individuals were enrolled in this study. Of the 45 TB patients, 15 were new cases with drug-susceptible active TB and 30 were relapsed cases (15 drug-susceptible and 15 multidrug resistant-TB). The age of study participants ranged from 21 to 68 years old. According to sex presentation, males were appreciably highly affected than females with a sex ratio of 2. The patients reported a mean recent weight loss of 8.9 kg. The Erythrocyte Sedimentation Rate was high in TB group, far exceeding the normal value. The results revealed that the number of CD3+ CD4+ T-cellssignificantly decreased whereas the level of blood Treg cells and expression of activation markers CD38 and HLA-DR on CD4+ T-cells significantly increased in TB group compared with the controlgroup (p&lt;0.05). The frequency of Treg cells was significantly higher in the TB group than the control group. Both the patients with new active TB and relapse TB demonstrated significantly higher levels of CD4+FoxP3+ Treg compared to healthy subjects (p&lt;0.05). A high and significant percentage of Treg cells were found in patients with DS active TB than patients with MDR relapse TB. Interestingly, the frequency of CD4+FoxP3+ cells also differs according to the sputum smear microscopy status. The presence of high numbers of Treg cells and corresponding high immune activation may be an unfavourable factor that can predispose individuals to different clinical forms of TB, including relapse TB.

Improving diagnosis and case management of patients with tuberculosis: A review of gaps, needs and potential solutions in accessing laboratory diagnostics

Tuberculosis (TB) recently surpassed HIV/AIDS as the deadliest infectious disease. Despite some advancements in technologies and programs, TB remains a global health epidemic that, without significant gains in better diagnostic and management, will not abate. This review describes the molecular diagnostic gaps, needs, and potential solutions for improving access to diagnosis and management of patients with drug susceptible and drug resistant TB. The ultimate goal is to improve laboratory diagnostics and better individualized managementof detected TB, and make an important contribution toward eliminating this global epidemic. RationaleTuberculosis persists as one of the world's most deadly infectious disease. To make substantive progress toward TB elimination and end the global tuberculosis epidemic by 2035, innovative approaches and technologies are essential. Among the various related and complementary scientific and clinical milestones toward elimination, including vaccine development and new therapeutic regimens, one of the greatest challenges is to address the gaps in existing diagnostics. Current diagnostic technologies fall short in meeting the complex nature of the disease and its epidemiologic profile. This review concentrates and outlines the priorities for development of laboratory diagnostic tools for screening and diagnosing TB. ApproachThe approaches and priorities described in this manuscript are based on identified gaps of current laboratory diagnosis of different clinical forms of TB. Closing these gaps will enable national programs to more efficiently diagnose TB, monitor treatment efficacy, and control drug resistance. Prioritization is based on technologies that address facilitate a more patient-centered approach, and are appropriate for low-resource and high-burden TB settings. New diagnostics must complement current or anticipated developments elsewhere and accelerate increased coverage, quality, and impact at the lower levels of the healthcare system.

ЭФФЕКТИВНОСТЬ ВНЕДРЕНИЯ АКТИВНОГО СКРИНИНГА И БЫСТРЫХ МЕТОДОВ ВЫЯВЛЕНИЯ СЛУЧАЕВ ТУБЕРКУЛЁЗА В РЕСПУБЛИКЕ ТАДЖИКИСТАН

Objective: To study the effectiveness of using active screening in identifying people with suspected tuberculosis, as well as express methods for diagnosing patients with tuberculosis in the Republic of Tajikistan. Methods: This study included persons who applied for medical institutions to primary health care (PHC) facilities for the period from 2011 to 2015 years in Dushanbe, Tursunzade, Khujand, Kanibadam and the regions of Gonchi, Mastchoh and Rudaki, which were screened for complaints and anamnestic data. All persons suspected of having tuberculosis underwent a complete clinical, x-ray examination and sputum research by two quick methods (microscopically and on the GeneXpert device), as well as sowing culture with subsequent determination of drug resistance on the Bactec MGIT apparatus. Results: Under our observations, there were 214,434 persons with suspicion of tuberculosis, from among which it was revealed 22,349 patients with different clinical forms of tuberculosis, which amounted to 10.4%. In the observed group of men there were 13887 (62.1%), women – 8462 (37.9%). Of the total number of patients, most (n=14100) included in the age group 19-44 years (63.1%) and 8249 people (36.9%) were from the age group of 45-69 years. Of the 22,349 tuberculosis patients, 65.5% suffered pulmonary tuberculosis with bacterial excretion, 25.1% – pulmonary tuberculosis without bacterial excretion and 9.4% – extrapulmonary tuberculosis. In 7.3% of cases, multiple drug resistance was detected, and in 92 patients (0.41%) – a combination of the active form of tuberculosis with HIV infection. Comparative study of the detection rate of new cases of tuberculosis over the same period in the study regions exceeded this indicator in other representative control regions twice. The beginning of the treatment after verification of the diagnosis was 3 days. Conclusion: The introduction of active screening in institutions of PHC facilities promotes a more effective integration of the phthisiatric services with the network of institutions of PHC facilities. In the implementation of active screening in 10.4% of cases, varifies different clinical forms of the disease. Keywords: Tuberculosis, screening, express methods, PHC, integration.

Observaciones respecto a las acciones terapéuticas y farmacológicas de la fluocortolona

Se ha efectuado en 30 pacientes un estudio clínico de los efectos terapéuticos y farmacológicos de la fluocortolona (Ultralan-(R) 1), nuevo esteroide sintético derivado de la corticosterona. Como tratamiento complementario de las drogas tuberculostáticas fue administrada a 18 enfermos con diversas formas clínicas de tuberculosis (pleuresía con derrame, meningitis, siembra miliar), en 6 pacientes con reacciones de hipersensibilidad, 2 con lupus eritematoso sistémico, 1 con dermotomiositis y 3 con leucemía. Se ha podido apreciar que la fluocortolona posee un buen efecto anti-inflamatorio con una relativa poca potencialidad de ocasionar la aparición de maniIestaciones secundarias. En el segundo día de administración, las determinaciones de 17-0HS y 17-KS urinarias mostraron que, a una dosis única matutina de 30 mgms., la fluocortolona tiene un efecto supresivo de la función suprarrenal algo menor que 2 mgms. de dexametasona, como son administrados en el test de Liddle. Al finalizar la tercera semana de un curso de 4 semanas de tratamiento, el valor promedio de los 17-0HS urinarios descendió hasta constituir un 20% del valor basal y 3 días después de la suspensión del mismo alcanzó a ser 66 %.

Tumour necrosis factor-alpha and nitric oxide response in different categories of tuberculosis patients

To compare the magnitude of tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) response in different categories of active tuberculosis (TB) patients by ex vivo experiment. New, relapsed (recurrent), miliary and pleural effusion TB cases were recruited with matched healthy controls. TNF-α and NO were measured from the culture supernatant of peripheral blood monocytes derived from cases and controls with and without challenge with live Mycobacterium tuberculosis H37Rv. TNF-α and NO production varied significantly among the different categories of TB patients. The magnitude was highest among patients with pleural effusion and lowest in miliary TB cases. In between, progressive decreases in response were noted in new and relapse cases. Overall, positive correlations between TNF-α and NO were noted among the diseased and healthy groups. Distinct TNF-α and NO levels appear to be associated with different clinical forms of TB and might help to assess prognosis and contribute to a better understanding of underlying immunopathological mechanisms.

Local Immune Responses in Human Tuberculosis: Learning From the Site of Infection

Host-pathogen interactions in tuberculosis should be studied at the disease site because Mycobacterium tuberculosis is predominately contained in local tissue lesions. Although M. tuberculosis infection involves different clinical forms of tuberculosis, such as pulmonary tuberculosis, pleural tuberculosis, and lymph node tuberculosis, most studies of human tuberculosis are performed using cells from the peripheral blood, which may not provide a proper reflection of the M. tuberculosis-specific immune responses induced at the local site of infection. A very low proportion of M. tuberculosis-specific effector T cells are found in the blood compared with the infected tissue, and thus there may be considerable differences in the cellular immune response and regulatory mechanisms induced in these diverse compartments. In this review, we discuss differences in the immune response at the local site of infection compared with the peripheral circulation. The cell types and immune reactions involved in granuloma formation and maintenance as well as the in situ technologies used to assess local tuberculosis pathogenesis are also described. We need to strengthen and improve the exploratory strategies used to dissect immunopathogenesis in human tuberculosis with the aim to accelerate the implementation of relevant research findings in clinical practice.

Genetic susceptibility to different clinical forms of tuberculosis in the Peruvian population

Racial variation, twin studies, segregation analyses, linkage and association studies all suggest that genetic factors play an important role in predisposition to tuberculosis. Many previous studies have been performed with pulmonary TB patients, as the most prevalent form of clinical TB (nearly 95%), and very few of them have considered extrapulmonary TB. The present study evaluates the effects of variation in eight candidate genes (LTA, TNF, IL1B, IL1RN, IL10, TGFB1, TIRAP and P2X7) with pulmonary, pleural, miliary and other extrapulmonary forms of TB in a Peruvian population from the North of Lima. 626 TB cases and 513 healthy controls were enrolled in this study. LTA+368 and IL10−592 were associated with different clinical forms of TB (P<0.05). LTA+368 genotype A/A was protective for pleural TB, LTA+368 G/A was correlated with susceptibility to miliary TB. Genotypes A/A and G/A were associated with protection and susceptibility respectively when considering all extrapulmonary TB forms versus either healthy controls or pulmonary TB patients. Carriers of IL10−592*C were under-represented among those with pulmonary TB and all TB forms (P<0.001). IL10−1082–IL10−592 haplotypes showed different distributions among patients with pulmonary TB and all TB forms (P<0.01) when compared to healthy controls. In addition, IL10−1082–IL10−592 haplotypes showed differences between pleural, miliary and all forms of extrapulmonary TB when compared with pulmonary TB (P<0.05). All findings are consistent with an under-representation of the IL10−1082*A–IL10−592*A haplotype in pulmonary TB patients. These results suggest that the polymorphisms LTA+368 and IL10−592, or variants in strong linkage disequilibrium, variably affect susceptibility to the differing clinical forms of TB in Peruvians.

Correlation between serum tumor necrosis factor alpha levels and clinical severity of tuberculosis

This study verified the correlation between the serum levels of TNF alpha and different clinical forms of tuberculosis. We described a group of 24 patients presenting several clinical forms of tuberculosis and a control group of 13 healthy individuals. The levels of TNF alpha were measured by bioassay method. The levels of TNF-alpha had significant differences between the tuberculosis and control groups. The patients with abnormal chest X-Ray findings had higher TNF alpha levels (15328.48 +/- 4602.19 pg/mL) when compared to patients with normal X-Rays (3353.18 +/- 1495.29 pg/mL) (p<0.05). Patients that lost weight had higher TNF alpha levels (15468.54 +/- 4580.54 pg/mL) than those that didn't loose weight (2904.98 +/- 1367.89) (p<0.05). The levels of TNF alpha were higher in patients with a positive PPD skin test than in those with a negative PPD test (p<0.05). There was a positive correlation between patients' clinical severity and the serum levels of TNF alpha. In patients with successive measurements of TNF alpha, we observed that there was a drop in cytokine levels, and also a clinical improvement concomitantly. We concluded that there was a correlation between serum TNF alpha levels and chest X-Ray alterations, loss of weight, positive PPD skin test and clinical severity in patients with tuberculosis. There was evidence of a worse clinical outcome in patients with tuberculosis that presented higher TNF alpha serum levels.

Decreased serum granulysin levels in childhood tuberculosis which reverse after therapy

Granulysin is a cytolytic protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Serum levels of granulysin are related to host cellular immunity. We used an ELISA to quantify granulysin serum levels in children with tuberculosis (TB), before and after chemotherapy. The study involved children affected by different clinical forms of TB (n=72) and healthy control children (n=150) from the same geographical area and of similar socio-economic background. Serum granulysin levels before the initiation of TB therapy were significantly lower in children with TB compared to controls, with the lowest levels being found in TB patients who were PPD skin test negative. No statistically significant differences were found between serum granulysin levels and clinical severity (mild/moderate or advanced pulmonary TB) or the clinical form (pulmonary or extra-pulmonary) of TB. At four months after completion of therapy, serum granulysin levels in children treated for TB were not significantly different to those observed in control children. This finding was paralleled by the increased in vitro mycobactericidal activity of sera from TB patients after completion of therapy. We propose that serum granulysin levels may provide a marker of disease activity in childhood TB and might be useful for monitoring improvement after chemotherapy.

Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment

Alterations of monocyte/macrophages have been reported in patients with tuberculosis (TB), but their significance is poorly understood. Blood mononuclear cells from patients with different clinical forms of TB, at various times of anti-TB treatment, and healthy tuberculin positive individuals, were double-stained for CD14 plus CD206, TLR-2, IFN-γR1, CD40, HLA-DR, CD36 and CD163, and analyzed by flow cytometry. Monocytes were infected with Mycobacterium tuberculosis H37Rv and 24 h later the phenotype, induction of necrosis and apoptosis and production of tumor necrosis factor TNFα, interleukin (IL)-10 and IL-12p40 were determined. TB patients presented higher percentage of CD14 + cells but lower percentage of CD14 +DR + and CD14 +CD36 + cells. Expression of CD14, HLA-DR and CD36 was decreased in TB patients. Normal percentages and expression were restored during anti-TB treatment. Monocytes from TB patients underwent necrosis and apoptosis after M. tuberculosis infection, whereas monocytes from healthy controls exhibited only apoptosis. Anti-TB treatment reverted necrosis. There were no differences between the various clinical forms of TB. In vitro M. tuberculosis infection decreased expression of the membrane molecules studied. HLA-DR and CD36 inhibition correlated with induction of apoptosis. Restoration of monocyte alterations during anti-TB treatment suggests that such alterations may be caused by the high M. tuberculosis load present during active disease.

Blood and urine samples as useful sources for the direct detection of tuberculosis by polymerase chain reaction

The aim of the study was to assess the utility of the polymerase chain reaction (PCR) assay in blood and urine for the diagnosis of tuberculosis (TB). We prospectively evaluated the usefulness of PCR performed in blood and urine samples from patients with proved or probable TB compared with a control group of patients. The PCR technique was performed using IS 6110 primers. We included in the study 57 patients (43 with definite TB and 14 with probable TB) and 26 controls. Blood and urine samples were drawn at the time of microbiologic diagnosis and 3, 6, 9, and 12 months later. Cultures were positive in the early period (<1 month after treatment) in 11 of 57 patients (19%) with probable or definite TB, in comparison with 42% of patients (24/57) who yielded a positive PCR ( P = 0.02). Urine samples increased the sensitivity of PCR determination in blood samples by 10%. The PCR in blood and/or urine was positive in 41% of patients with pulmonary TB, in 36% of patients with extrapulmonary TB, and in 50% of patients with disseminated TB. Mycobacterium tuberculosis was still detectable by PCR in 5 of 13 patients with cured TB after 1 or more months of antituberculous treatment. The PCR detection of M. tuberculosis in blood and urine samples is useful for the diagnosis of different clinical forms of TB, mostly in those patients in which sample extraction is difficult or requires aggressive techniques. The sensitivity of this technique could be improved studying more than 1 sample in each patient, even after initiating an antituberculous treatment.

Association between SLC11A1 polymorphisms and susceptibility to different clinical forms of tuberculosis in the Peruvian population

Polymorphism in SLC11A1 has been implicated in host susceptibility to tuberculosis. We have studied associations between INT4, D543N, and 3′UTR polymorphisms of SLC11A1 and different clinical forms of TB. Analysis used 507 patients with pulmonary TB, 123 with extra pulmonary TB and 513 controls. INT4 and D543N showed allelic association with pulmonary TB ( P = 0.02 and 0.03 respectively). INT4–D543N–3′UTR haplotypes showed an association with pulmonary TB ( P = 0.03). No association of SLC11A1 with miliary TB was observed, and a possible association of D543N to the pleural form ( P = 0.08) was suggested. These results support association between SLC11A1 and TB, particularly to the common pulmonary form.

Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Tuberculosis (TB)/HIV co-infection significantly changes the natural history of both diseases. Proper comprehension and clinical management of co-infected TB/HIV patients is still a challenge, particularly in places like Brazil, where both types of infection are prevalent. Evaluate the frequency of the clinical forms of TB in HIV-infected patients; correlate the clinical forms of TB with the level of immunodeficiency; evaluate the response to therapy with different regimens for the treatment of TB; identify potential prognostic factors in TB/HIV patients. The following data were collected at the beginning of the study: medical history, epidemiological background, physical examination, and laboratory evaluation (complete blood cell count, T lymphocyte subsets, viral load and tuberculin test). Monthly clinical follow-up was performed, with attention to adverse reactions to tuberculostatic drugs. TCD4+/CD8+ lymphocyte counts and quantification of the viral load were performed after 2, 4, 6, 10 and 15 months of follow-up. The study population consisted of 78 patients (45 males and 33 females) and their mean age was 36.4 +/- 7.9 years The mean TCD4+ count values were higher in patients with the cavitary pulmonary form and lower in patients with disseminated forms. There were no significant differences in the mean TCD8+ cells counts . in the different clinical forms of TB. However, the mean laboratory values for hemoglobin, hematocrit and leucocytes at study entry did differ significantly among the various clinical forms of TB. At the end of the trial, the Tb recovery rate was of 78%, with four cases (5%) of treatment failure, eight (11%) treatment discontinuations and five deaths (6.4%). The highest rate of treatment failure (75%) was observed among patients with the disseminated form. Lower TCD4+ mean values were observed in cases of treatment failure and death. There was a correlation between the TCD4+ cell values and the TB outcome at the six time points. TCD8+ (cells/mm(3)) mean values assessed at the six time points in relation to the TB outcome indicated (non-significantly) lower values in patients who progressed to treatment failure. Considering the different TB outcomes, there was a significant correlation between TCD8+ values at the first and third assessments. Lower mean values of hemoglobin, hematocrit, platelet and leukocytes were observed among the cases of treatment failure than in patients who recovered. The variables hemoglobin, hematocrit, leukocytes and platelets were significantly different among the groups. The pulmonary forms of TB were most frequent in HIV infected patients; the extrapulmonary, associated and disseminated forms were predominantly seen in patients with a more severe level of immunosuppression. The TB recovery rate in HIV infected patients was similar to the expected rate in non-infected individuals. The best results were obtained when regimens containing rifampicin were used. Pancytopenia and low levels of TCD4+ and TCD8+ lymphocytes at the initial time point of the study were correlated with an unfavorable outcome of TB, and therefore they can be considered potential prognostic factors. However, the of TCD8+ lymphocyte values were the most important variable assessed.

CD14 gene promoter polymorphism in different clinical forms of tuberculosis

Mycobacterium tuberculosis interacts with monocyte–macrophages through cell surface molecules including CD14. A soluble form of CD14 (sCD14) exists in human serum, and higher amounts of it are found in tuberculosis. A polymorphism on CD14 gene promoter was associated with increased sCD14 levels in some diseases. To evaluate whether this polymorphism associates with tuberculosis, its clinical forms, and increased sCD14, genotype/allele frequencies in tuberculosis patients were compared with the controls. Results confirmed increased levels of sCD14 in patients with tuberculosis, and those with miliary tuberculosis had the highest levels. sCD14 decreased to normal levels after anti-tuberculosis treatment. No association was found between the CD14 polymorphism and tuberculosis or sCD14 levels. Results suggest that sCD14 may be involved in anti-tuberculosis immune response, but its increase is a consequence of infection rather than a predisposed genetic trait. Measuring sCD14 in tuberculosis may help monitor anti-tuberculosis treatment.

Cell-mediated immune responses and cytotoxicity to mycobacterial antigens in patients with tuberculous pleurisy in Brazil

Evaluating human immune response to defined Mycobacterium tuberculosis antigens in patients with different clinical forms of tuberculosis may help in elucidating pathogenesis and in vaccine development. In the present report we evaluated the lymphocyte proliferation, cytokine production and natural killer cell cytotoxicity as parameters to screen four mycobacterial recombinant antigens. Pleural fluid mononuclear cells (PFMC) and peripheral blood mononuclear cells (PBMC) from 13 HIV-negative patients with tuberculous pleurisy, living in a tropical region of Brazil were used in these assays. Crude M. tuberculosis antigen and recombinant 70-, 65- and 38-kDa mycobacterial antigens, induced greater proliferation in PFMC than in PBMC. IFN-γ, TNF-α, IL-4 and IL-10 were evaluated in the PFMC supernatants stimulated by these antigens. Both crude and 70-kDa antigens induced higher levels of IFN-γ, TNF-α and IL-10. There was a significant positive correlation between IFN-γ and the proliferative response induced by crude M. tuberculosis antigen, and an inverse correlation was identified between IL-10 and cell proliferation. IL-4 was not detected in the supernatants of pleural fluid mononuclear cell cultures stimulated by either crude, or recombinant antigens. TNF-α was detected in variable amounts in supernatants of PFMC stimulated by all antigens tested. Natural killer cytotoxicity was induced by both crude and 70-kDa antigen. Our results demonstrate that cells present at the site of disease recognized three of the antigens screened, as shown by lymphocyte proliferation and production of regulatory and inflammatory cytokines, and the results obtained with PFMC were consistently higher than those obtained with homologous PBMC.

Serological diagnosis of childhood tuberculosis by estimation of mycobacterial antigen 60-specific immunoglobulins in the serum

Setting: An ELISA assay based on mycobacterial antigen 60 (A60) for the estimation of specific immunoglobulins in the serum has been used successfully for the rapid diagnosis of tuberculosis in studies done predominantly in Western countries. In a recent Indian study, encouraging results were reported in adult tuberculosis. Objective: To evaluate the utility of this ELISA test for rapid diagnosis of different clinical forms of tuberculosis in Indian children. Design: ELISA test based on mycobacterial A60 was used to estimate specific IgM, IgA and IgG antibodies in the sera obtained from 452 cases of tuberculosis and 161 controls in the paediatric population of Delhi, India. Results: Of the 161 controls, only 7.4% were positive for IgM, 4.3% for IgG, 3.7% for IgA and 8% when a combination of IgM and IgA was considered. Of 58 cases of definite pulmonary tuberculosis, 55.2% were positive for IgM, 32.7% for IgG, 36.2% for IgA and a high positivity of 72.4% was seen when IgA and IgM estimations were combined. The corresponding figures in 150 cases of definite extrapulmonary tuberculosis were 57.3%, 36.6%, 38% and 76.6%. A relatively weak serology was observed in 244 cases of probable tuberculosis. A very high positivity (95%) was seen in acid-fast bacilli-positive cases of tuberculosis. Conclusions: Our findings point to a very good specificity (92%) and a reasonably good sensitivity (75.5%) of the test when combined IgM and IgA antibody titres are considered in the diagnosis of childhood tuberculosis.

Diagnostic utility of the estimation of mycobacterial Antigen A60 specific immunoglobulins IgM, IgA and IgG in the sera of cases of adult human tuberculosis

Setting: An ELISA assay based on mycobacterial Antigen A60 for the estimation of Mycobacterium-specific immunoglobulins in the serum has been used successfully for the rapid diagnosis of tuberculosis in studies done in the Western countries. There are hardly any similar large scale studies in India. Objective: To evaluate the utility of this ELISA test for rapid diagnosis of different clinical forms of tuberculosis in an adult Indian population. Design: ELISA test based on mycobacterial antigen A60 (Anda Biologicals, France) was used to estimate specific IgM, IgA and IgG antibodies in the sera obtained from 337 cases of tuberculosis and 131 controls in the population of Delhi (India). Results: Of the 131 controls, only 9.9% were positive for IgM, 7.6% for IgG, 6.1% for IgA and 9.9% when an IgA and IgG combination was considered. Of 122 cases of active pulmonary tuberculosis, 41% were positive for IgM, 86.8% for IgA, 88.5% for IgG and a very high positivity (98.3%) was seen when IgA and IgG estimations were combined. A relatively low seropositivity was observed in 25 cases of pleural tuberculosis. The corresponding figures in 130 cases of extrapulmonary tuberculosis were 22.3%, 68.4%, 73.8% and 86.15%. When 60 cases of pulmonary tuberculosis who had been successfully treated with antituberculosis drugs were analyzed the rates of seropositivity fell to 11.6%, 46.6%, 58.3% and 66.6% respectively. Conclusion: Our findings point to a very good sensitivity (91.6%) and specificity (90.0%) of the test when combined IgA and IgG antibody titres are considered, to detect cases of adult tuberculosis. The role of IgM estimation can be restricted to the detection of cases of reactivation of tuberculosis.

Prospective study of drug-resistant tuberculosis in a Spanish urban population including patients at risk for HIV infection.

From January 1988 to October 1992, the primary resistance to first-line antituberculous drugs in 501 tuberculous patients was evaluated prospectively. Three-hundred and seventeen patients were HIV-negative and 184 were HIV-positive; these patients had several different clinical forms of tuberculosis. Moreover, the acquired resistance to antituberculous drugs was studied in 295 non-AIDS patients and in 42 AIDS patients with evidence of antecedent tuberculosis treatment. The data indicated that during these five years there was no consistent and clear-cut trend toward greater frequency of primary drug resistance to any of the first-line antituberculous drugs. Primary drug resistance in HIV-positive patients (7.1%) did not differ significantly (p > 0.05) from that found in HIV-negative patients (8.2%). Among HIV-positive patients, the acquired drug resistance pattern was similar to that detected in HIV-negative patients although the frequency of resistance in the former (69%) was significantly higher (p < 0.01). During the study, resistance to isoniazid was almost constant in the acquired-resistance cases and was frequently associated with resistance to other drugs. Furthermore, the acquired resistance to isoniazid was often of a higher level (1 to 10 mg/l) than the primary resistance (0.2 mg/l), and those strains were usually catalase and peroxidase negative.