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PubMed2006

Automatic identification of Mycobacterium tuberculosis by Gaussian mixture models.

Tuberculosis and other kinds of mycobacteriosis are serious illnesses for which early diagnosis is critical for disease control. Sputum sample analysis is a common manual technique employed for bacillus detection but current sample-analysis techniques are time-consuming, very tedious, subject to poor specificity and require highly trained personnel. Image-processing and pattern-recognition techniques are appropriate tools for improving the manual screening of samples. Here we present a new technique for sputum image analysis that combines invariant shape features and chromatic channel thresholding. Some feature descriptors were extracted from an edited bacillus data set to characterize their shape. They were statistically represented by using a Gaussian mixture model representation and a minimal error Bayesian classification procedure was employed for the last identification stage. This technique constitutes a step towards automating the process and providing a high specificity.

Bacteriological Techniques↗

PubMed1999

Risk factors for tuberculosis in patients with AIDS in London: a case-control study.

OBJECTIVE: To identify risk factors for the acquired immune-deficiency syndrome (AIDS) associated with tuberculosis, in patients with AIDS attending 11 of the largest human immunodeficiency virus (HIV)/AIDS Units in London. DESIGN: Case-control study nested in a retrospective cohort of 2048 HIV-1 positive patients. Cases were defined as patients with a definitive diagnosis of tuberculosis, and controls as patients with AIDS and without tuberculosis during follow-up. RESULTS: Of 627 patients diagnosed with AIDS, 121 had a definitive diagnosis of tuberculosis. Significant risk factors for tuberculosis in the univariate analysis were sex, ethnicity, age, HIV exposure category and hospital attended, and in the multiple regression analysis ethnicity, age and hospital attended. African ethnicity was the strongest risk factor for tuberculosis (adjusted odds ratio [AOR] 5.9, 95% confidence interval 3.4-10.2). The risk of tuberculosis was higher in the younger age groups (test for trend P < 0.001). The hospital-associated risk of tuberculosis was more heterogeneous in the non-African group, and non-Africans attending Hospital 1 had an increased risk of tuberculosis which was statistically significant. CONCLUSIONS: The risk factors for AIDS-associated tuberculosis in London are sub-Saharan African origin, younger age group, and, among the non-Africans only, attending one hospital in east London. Different transmission patterns and mechanisms for the development of tuberculosis may operate in different settings depending on the background risk of tuberculous infection. Screening for tuberculosis infection and disease among HIV-positive individuals in London is important for the provision of preventive or curative therapy, and prophylaxis policies need to be designed in accordance with the transmission patterns and mechanisms of disease.

Acquired Immunodeficiency Syndrome↗

PubMed2004

The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs.

A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and designated Mtb72F was tested for its protective capacity as a potential adjunct to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant enhanced the Th1 response to BCG in mice but did not further reduce the bacterial load in the lungs after aerosol challenge infection. In the more stringent guinea pig disease model, rMtb72F delivered by coadministration with BCG vaccination significantly improved the survival of these animals compared to BCG alone, with some animals still alive and healthy in their appearance at >100 weeks post-aerosol challenge. A similar trend was observed with guinea pigs in which BCG vaccination was boosted by DNA vaccination, although this increase was not statistically significant due to excellent protection conferred by BCG alone. Histological examination of the lungs of test animals indicated that while BCG controls eventually died from overwhelming lung consolidation, the majority of guinea pigs receiving BCG mixed with rMtb72F or boosted twice with Mtb72F DNA had mostly clear lungs with minimal granulomatous lesions. Lesions were still prominent in guinea pigs receiving BCG and the Mtb72F DNA boost, but there was considerable evidence of lesion healing and airway remodeling and reestablishment. These data support the hypothesis that the coadministration or boosting of BCG vaccination with Mtb72F may limit the lung consolidation seen with BCG alone and may promote lesion resolution and healing. Collectively, these data suggest that enhancing BCG is a valid vaccination strategy for tuberculosis that is worthy of clinical evaluation.

Animals↗

PubMed1980

Some qualitative changes of indicators of the epidemiological position as regards tuberculosis in Czechoslovakia and their perspectives.

The application of comprehensive provisions in TB control in Czechoslovakia led to a marked decline of its quantitative and qualitative epidemiological indicators. The incidence of TB declined from 191.1 in 1951 to 46.3 in 1978 per 100 000 population. The number of newly detected cases of TB in child groups declined between 1958 and 1978 from 78.2 to 5.5 per 100 000 children. The number of cases of tuberculous meningitis declined during this period in the entire population from 97 to 5 cases. There was a markes shift of newly detected cases into higher age groups. The prevalence of bacillary TB decline from 211.1 in 1956 to 39.0 in 1977 per 100 000 population. According to mathematical and statistical calculations the incidence of TB will preserve also in future its declining trend whereby the values at the turn of the century will be at the borderline of the lower half of the value recorded at present.

Adolescent↗

PubMed2001

[The immunotherapeutic effect of Mycobacterium vaccae vaccine on initially treated pulmonary tuberculosis].

OBJECTIVE: To evaluate the effect and safety of Mycobacterium vaccae vaccine (M. vaccae vaccine) on initially treated pulmonary tuberculosis. METHODS: 342 cases of initially treated pulmonary tuberculosis with smear and culture positive were divided into immunotherapy (M, 171 cases) group and control (C, 171 cases) group at random pair. The group M were treated by chemotherapy with a regimen of 2HRZE/2HR and immunotherapy with M. vaccae vaccine for 6 months. The group C were treated only by chemotherapy with a regimen of 2HRZE/4HR. RESULTS: The sputum smear-negative conversion rates in group M 1, 2 and 6 months after treatment were 36.8%, 80.1% and 98.2% respectively; those in group C were 19.9%, 54.4% and 98.8% respectively. The sputum culture-negative conversion rates in group M 1, 2 and 6 months after treatment were 47.4%, 85.9% and 99.4% respectively; those in group C were 19.3%, 67.8% and 98.8% respectively. The sputum-negative conversion rates of group M were significantly higher than those of group C after 1 and 2 months treatment (P < 0.01), but there were no statistically significant differences between the two groups at the end of 6 months after treatment (P > 0.05). Compared with group C, group M were better in improving of X-ray manifestation, increasing of the percentage of CD(3) and CD(4) T cell and the ratio CD(4)/CD(8) and closing of cavity (P < 0.01). The side effects of M. vaccae vaccine were rare and slight. The bacteriological relapse rates in group M, C were 3.0%, 5.6% respectively (P > 0.05). CONCLUSIONS: As an adjunct to chemotherapy, immunotherapy with M. vaccae vaccine is helpful for patient with initially treated pulmonary tuberculosis, and it is possible to further shorten the duration of short-course chemotherapy with a combination of chemotherapy and M. vaccae vaccine.

Adolescent↗

PubMed2004

B-lymphocytes and co-stimulatory molecules in Mycobacterium tuberculosis infection.

SETTING: The immunological mechanisms that lead to the control of Mycobacterium tuberculosis infection are not well known. OBJECTIVE: To study the role of lymphocyte subsets and co-stimulatory molecules in M. tuberculosis infection. DESIGN: In 35 patients with pulmonary tuberculosis (PTB) and their contacts, 29 persons with tuberculin skin test conversion (TSTC) and 20 healthy individuals with negative tuberculin skin test (NTST), we studied T-lymphocyte subsets (CD3, CD4, CD8, alphabetaTCR and gammadeltaTCR), B-cells, monocytes and co-stimulatory molecules CD28 and CD86 in peripheral blood. The results were analysed at univariate and multivariate level through discriminant analysis. RESULTS: At univariate level, compared with TSTC and NTST, PTB patients presented a decrease in CD4+ T-cells (P = 0.002), and B-cells (P = 0.02 and 0.001, respectively). With regard to NTST subjects, PTB patients also showed a decrease in the percentage of CD86+ monocytes (P = 0.02) and an increase in the percentage of CD86+ B-lymphocytes (P = 0.02). At multivariate level, CD4+ T-lymphocytes showed statistical differences between PTB and TSTC subjects (P = 0.001). B-lymphocytes were discriminant between PTB and NTST (P < 0.001) and between TSTC and NTST individuals (P = 0.01). CONCLUSION: The number of total CD4+ T-cells is the best discriminant parameter for distinguishing between disease and infection, whereas the B-cell count is the best between healthy and infected individuals.

Adult↗

PubMed2002

Predictive model to identify positive tuberculosis skin test results during contact investigations.

CONTEXT: Budgetary constraints in tuberculosis (TB) control programs require streamlining contact investigations without sacrificing disease control. OBJECTIVE: To develop more efficient methods of TB contact investigation by creating a model of TB transmission using variables that best predict a positive tuberculin skin test among contacts of an active TB case. DESIGN, SETTING, AND SUBJECTS: After standardizing the interview and documentation process, data were collected on 292 consecutive TB cases and their 2941 contacts identified by the Alabama Department of Public Health between January and October 1998. Generalized estimating equations were used to create a model for predicting positive skin test results in contacts of active TB cases. The model was then validated using data from a prospective cohort of 366 new TB cases and their 3162 contacts identified between October 1998 and April 2000. MAIN OUTCOME MEASURE: Tuberculin skin test result. RESULTS: Using generalized estimating equations to build a predictive model, 7 variables were found to significantly predict a positive tuberculin skin test result among contacts of an active TB case. Further testing showed this model to have a sensitivity, specificity, and positive predictive value of approximately 89%, 36%, and 26%, respectively. The false-negative rate was less than 10%, and about 40% of the contact workload could be eliminated using this model. CONCLUSIONS: Certain characteristics can be used to predict contacts most likely to have a positive tuberculin skin test result. Use of such models can significantly reduce the number of contacts that public health officials need to investigate while still maintaining excellent disease control.

Adolescent↗

PubMed1999

Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.

Adolescent↗

PubMed1999

Tuberculosis in Lebanese jails: prevalence and risk factors.

A survey was conducted in 1995 to assess the prevalence of TB infection using the PPD skin test infection among 3931 inmates in all 21 jails in Lebanon. Forty-five percent of participants had a positive PPD skin test. The likelihood of testing positive was higher among men versus women, and among those who had been incarcerated for more than 3 years versus less than that. Compared to prisoners whose usual residence was Central Lebanon, those from North Lebanon and those from outside Lebanon (mostly Syria and Egypt) had a higher risk for PPD positivity, those from Bekaa a lower risk, and those from South Lebanon about the same risk. Among those with positive PPD tests, 7% had abnormal chest X-rays suggestive of active infection. Results suggest that TB infection is an important health problem in correctional facilities in Lebanon and that special control programs should target North Lebanon. The importance of screening the incarcerated population with chest X-rays rather than PPD skin tests is discussed.

Adult↗

PubMed2006

[Evaluation of the control measures adopted against an epidemic of AIDS-related multidrug-resistant tuberculosis in a Latin-American hospital].

BACKGROUND: Since 1992 AIDS-related multidrug-resistant tuberculosis (MDRTB) has been detected among patients admitted to the Hospital Muñiz in Buenos Aires (Argentina). The aim of the present study was to evaluate the effectiveness of the control measures adopted against the nosocomial spread of MDRTB/AIDS, which affected 803 patients between 1992 and 2002. METHODS: An action plan was applied that included bacilloscopy screening on admission, isolation rooms for patients with TB/AIDS, an isolation ward for patients with MDRTB/AIDS, a radiometric method for the diagnosis of multidrug-resistance, a reserve supply of second line drugs, and respiratory protection for health care workers. RESULTS: Between 1995 and 2002, a statistically significant decreasing trend in cases of MDRTB/AIDS and admissions for TB/AIDS was observed (33.9% vs 80.5%). Mortality among patients with MDRTB/AIDS also significantly decreased. Bacilloscopy screening allowed the diagnosis of 63.4% of patients admitted with TB/AIDS. Respiratory isolation facilities and effective treatment of patients with MDRTB diagnosed through the radiometric method were progressively implemented. Admission of patients with AIDS showed no significant variations throughout the study period. The CD41 count of patients requiring admission did not vary significantly. CONCLUSION: The nosocomial epidemic curve of MDRTB in patients with AIDS significantly decreased, despite the persistence of susceptible patients with low CD41 levels. The decreasing tendency of MDRTB/AIDS cases could be attributed to the impact of the control measures implemented.

AIDS-Related Opportunistic Infections↗

PubMed1992

[Chemoprophylaxis of tuberculosis: compliance to treatment in the pediatric population].

We have reviewed the success of tuberculosis chemoprophylaxis in 369 children. These children ranged from 4 months to 14 years of age and had been prescribed chemoprophylaxis with Isoniazide at 10 mg/kg/day. Out of these, 258 (69.91%) finished the prophylaxis and 111 (30.08%) did not. Taking into account the reason for the consultation, of those who sought assistance due to contact with a patient with tuberculosis, 70.33% performed the treatment and 29.60% did not. For those in which the reason was a positive Mantoux, the data were 68.1% and 30.8%, respectively. No statistically significant differences were found between the two groups. We feel that the relatively high rate of noncompliance in our patients is a matter of concern. At the present time, chemoprophylaxis with Isoniazide is the best method available for the prevention of tuberculosis. We emphasize the need for its proper performance. We report several measures, such as the determination of Isoniazide metabolites in urine, which may be beneficial for better control and follow-up of these patients.

Adolescent↗

PubMed1993

Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis.

The protective effect of BCG against tuberculosis (TB) estimated in randomized controlled trials and observational studies ranges from negative to close to a 100%. One of the many explanations offered for this is that different immunological mechanisms may be associated with protective effect against different forms and sites of disease. In this investigation, we recalculated vaccine protective effect separately for pulmonary disease and for meningeal/miliary disease in randomized controlled trials and case-control studies, tested for heterogeneity in site-specific estimates of protective effect and calculated a summary measure when appropriate. We found protective effect against pulmonary disease to be heterogeneous to a statistically significant degree, and thus we did not calculate a summary measure of protection. Protective effect against meningeal and miliary TB was higher than against pulmonary disease and, except for a single study with two cases only, appeared to be homogenous. Summary BCG protective effect against miliary or meningeal TB in randomized controlled trials was 86% (95% confidence interval [CI] 65, 95) and in case-control studies 75% (95% CI: 61, 84). The fact that protective effect appeared to be homogeneous against meningitis and miliary TB but not against pulmonary disease may result from the fact that patients with meningitis are on average younger and thus less likely to have been exposed to atypical bacteria; to a waning of the protective effect of BCG; or from the diversity of mechanisms of pathogenesis of pulmonary disease, which can originate from reinfection, reactivation or primary progression.

BCG Vaccine↗

PubMed1985

[Controlled study comparing 3 daily chemotherapy regimens for six months in pulmonary tuberculosis in routine practice in Algiers. Results at 30 months].

Three anti-tuberculous regimens were compared in Algiers. The three regimens use Isoniazid and Rifampicin every day for six months; two of them used a third drug, Ethambutol or Pyrazinamide for the first three months. The results at 12 months after cessation of chemotherapy have already been reported. At 30 months (or 24 months after the end of treatment) the results were analysed for 513 cases: in 27 cases (5%) there was a relapse or therapy failed. Of 21 relapses 13 occurred in the first six months of follow up, four during the next six months, three during the third and one in the final six months. No further relapse was seen between the thirtieth and forty second months. All the cases of failure or relapse had received an additive chemotherapy. Two patients were on chemotherapy again for a relapse noted in under six months; the other 25 patients had a satisfactory outcome after receiving a regime of six to 12 months containing Rifampicin in 21 cases or a regime 12 months without Rifampicin in four cases. There was no statistically significant difference between the three therapeutic series for those cases with tubercle bacilli initially sensitive to the antituberculous drugs. On the other hand, for primary Isoniazid resistance a third drug is essential during the initial treatment. In the overall analysis pyrazinamide was as effective as Ethambutol in avoiding failure due to primary drug resistance and relapses up to 30 months.

Antitubercular Agents↗

PubMed1990

Five year results of a 3-month and two 5-month regimens for the treatment of sputum-positive pulmonary tuberculosis in south India.

A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed, sputum-positive pulmonary tuberculosis. The patients were allocated at random to one of three regimens: a) Rifampicin, streptomycin, isoniazid and pyrazinamide daily for 3 months (R3); b) the same regimen as above but followed by streptomycin, isoniazid and pyrazinamide twice-weekly for a further period of 2 months (R5); c) the same as R5 but without rifampicin (Z5). A bacteriological relapse requiring treatment occurred by 5 years in 16.8% of 113 R3, 5.2% of 97 R5, and 20.0% of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially. The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant (p less than 0.01 for both). Considering patients with organisms initially resistant to streptomycin or isoniazid or both, 7 of 52 patients (4 R3, 2 R5, 1 Z5) had a bacteriological relapse requiring retreatment.

Adolescent↗

PubMed2006

Protective effect of Bacillus Calmette-Guerin (BCG) vaccination in children with extra-pulmonary tuberculosis, but not the pulmonary disease. A case-control study in Rosario, Argentina.

A hospital-based case-control study was carried out at the Vilela Children's Hospital in Rosario, Argentina, to measure the protection conferred by BCG vaccination against tuberculosis (TB). The study included 148 newly diagnosed cases of TB (75 males and 73 females, mean age 3.34+/-2.97 years, S.D.), 134 of them with pulmonary TB and 14 cases with extra-pulmonary disease. Controls (425 males and 357 females, 3.39+/-2.98 years) were selected randomly among children who attended to the Hospital showing, neither respiratory diseases nor any other infectious illnesses. Information on BCG vaccination history was assessed from scars or immunisation records. All participants were negative to human immunodeficiency virus and belonged to the lower and upper-lower socioeconomic status, being similar in place of residence and ethnic characteristics. Rate of vaccinated children was 92.6% of cases and 94.5% of controls (3.4 and 3.9% of them without scars, respectively). Regarding the total cases, the protective association between BCG and TB was statistically insignificant, as was for the pulmonary form. Among cases with extra-pulmonary disease, vaccine effectiveness attained significance [79% (95% CI=26-94)], no matter their age, sex or nutritional status. BCG vaccination exerted a beneficial role in extra-pulmonary TB, even in children not seriously undernourished.

Age Factors↗

PubMed2006

Cost-effectiveness analysis of an alternative tuberculosis management strategy for permanent farm dwellers in South Africa amidst health service contraction.

AIM: To establish the cost-effectiveness of lay health workers (LHWs) in conjunction with the current, local tuberculosis (TB) control programme, amidst health service contraction. METHOD: A cost-effectiveness analysis, comparing direct time costs of the current TB management strategy among permanent farm dwellers, with an intervention, whereby LHWs are involved in TB control activities on farms. Measure of effectiveness was case finding and cure rates of adult new smear-positive (NSP) TB cases, alongside a randomized control trial (RCT): RESULTS: The observed cost reduction to the Boland Health District was 74% per case detected and cured on the intervention farms relative to the control farms. Intervention farms reached 83% successful treatment completion rate, control farms 65%. Although the successful treatment adherence was significantly different (18% letter). The improved case detection and cure rates were not statistically significant (chi-squared test). Direct LHW costs are borne by farmers. Farmers were motivated to bear costs by reduced job absenteeism and other positive side-effects. Even without outcome improvements costs per case cured were 59% lower on the intervention farms. CONCLUSION: TB control has suffered from budget reductions in South Africa. It is critically important to develop cost-effective strategies to reduce the TB burden. Costs to public budgets can be substantially reduced while maintaining or improving case detection and treatment outcomes, by using farm-based LHWs.

Adolescent↗

PubMed1975

Immunological features of asthma (Part II). A report to the Research Committee of the British Thoracic and Tuberculosis Association.

A serological comparison was made of two groups of 120 matched asthmatic and healthy subjects, between the ages of 20 and 49 years and matched for age and sex, in terms of serum total levels of IgG, IgM, IgA, IgD and IgE and of specific antibody levels in each immunoglobulin class to five common UK allergens. The relationship of clinical features to the serological tests was also examined in the asthmatic subjects. The following statistically significant findings were shown. The patients had higher levels than the controls of total globulins and of IgG, IgA and IgD but not IgM. In both patients and controls the females had higher IgM levels than the males. The total IgE levels were higher in patients than in the controls and the male patients had higher levels than the female patients. Total IgE levels were also related, to the numbers of first degree relatives with asthma, hay fever and eczema, to the severity of hay fever and to the amount of time off work in the male patients. In those male patients with exercise induced asthma the total IgE levels were lower than in those not showing this reaction. As for the other immunoglobulins, the only significant differences were a higher IgG level in patients with FEV1 or PFR greater than 50% predicted and a higher IgD level in patients with hay fever. Radio-immunodiffusion tests for specific precipitins were positive for Dermatophagoides pteronyssinus in comparable numbers of asthmatics (25.8%) and controls (21.7%). Positive precipitin tests were uncommon in tests with extracts of grass pollen, Aspergillus fumigatus, cat and dog hair in the patients and even less so in the controls. Positive RAST tests for specific IgE antibodies were obtained in patients and controls respectively, against D. pteronyssinus 59% and 11%, grass pollen 37.0 and 12%, and A. fumigatus 6% and 4%. The male patients showed the closest significant relationship of specific IgE to D. pteronyssinus and the history of house dust allergy, positive skin test and nasal test. In the females only the skin and specific IgE tests were related. Both sexes showed a significant association between specific IgE to grass pollen and positive skin tests and nasal tests, but only the males showed an association with the history. The sizes of skin test weal to D. pteronyssinus were related to the levels of specific IgE antibody. No differences were found between the four skin test groups and between the asthmatics and the control subjects in the incidence of bacterial precipitins and auto-antibodies.

Adult↗

PubMed2004

VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis among the Chinese Han population: a case-control study.

OBJECTIVE: To explore the potential role of vitamin D receptor (VDR) gene and natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms in susceptibility to pulmonary tuberculosis (PTB) in the Chinese Han population. DESIGN: In an unmatched case-control study, 120 well defined PTB patients and 240 unrelated normal controls were enrolled. Information on potential risk factors of PTB was collected using a standard questionnaire. Genetic polymorphisms of VDR gene (TaqI and FokI) and NRAMP1 gene (INT4, D543N and 3'UTR) were analysed using PCR and RFLP. Unconditional logistic regression was performed, and odds ratios (ORs), their 95% confidence intervals (CI) and P values were estimated using maximum likelihood methods. RESULTS: Univariate analysis demonstrated that FokI-ff homozygotes, D543N G/A and 3'UTR TGTG+/del heterozygotes occurred more frequently in patients than in controls. The crude ORs were 2.345 (95%CI 1.222-4.499), 2.590 (95%CI 1.043-6.434) and 1.890 (95%CI 1.171-3.051), respectively, compared with their corresponding common genotypes. The P values were 0.033, 0.041 and 0.030, respectively. After adjusting for exposure history and BCG immunisation in the multivariate analysis, the adjusted ORs were 4.625 (95%CI 1.737-12.312), 2.415 (95%CI 1.079-8.759) and 2.187 (95%CI 1.146-4.175), with P values of 0.002, 0.036 and 0.018, respectively. Neither univariate nor multivariate analysis disclosed any significant association between the disease and TaqI or INT4. CONCLUSIONS: Polymorphisms in the VDR and NRAMP1 gene are statistically associated with susceptibility to PTB in the Chinese Han population.

Adult↗