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[Problems of HIV infection and tuberculosis (TB) in Asia--an epidemetric model analysis of the impact of HIV infection on TB control].

The widespread HIV infection in some developed and developing countries is posing serious problems for the control of TB. An edpidemetric model was built to simulate the dual epidemics of HIV infection and TB in the developing world's population. It was shown that HIV infection may greatly increase the prevalence of TB and the risk of TB infection. The impact of epidemics of HIV infection and the effectiveness of TB control measures were quantified with the cumulative prevalence of TB and the extent of its reduction. The relevance of epidemetric models in the planning of policies for the control of TB is discussed.

Asia↗

Comparison of three composite compliance indices in a trial of self-administered preventive therapy for tuberculosis in HIV-infected Ugandan adults. Uganda-Case Western Reserve University Research Collaboration.

Compliance with tuberculosis preventive therapy in a randomized placebo-controlled trial in 2736 HIV-infected Ugandans was measured using urinary isoniazid metabolite testing, clinic attendance, and self-report. Overall, 77% of urine tests were positive, subjects kept 85% of their scheduled visits while on therapy, and 69% reportedly never forgot to take their medication. Different strategies were used for constructing three composite compliance indices in active arms: (1) an unweighted index of the summed scores on scaled compliance measures; (2) a weighted index using weights obtained from a survey of experts on tuberculosis; and (3) a statistically weighted index using principal components analysis. Composite indices were evaluated for reliability, validity, and practical utility. Understanding of the regimen, study arm, subsequent follow-up, tuberculosis status, and urine spot-check result were associated with composite compliance scores. The unweighted index in this study performed as well as the weighted indices.

AIDS-Related Opportunistic Infections↗

Case-control study of BCG vaccination as a risk factor for leprosy and tuberculosis in western Kenya.

A case-control study was carried out in western Kenya to measure the protection imparted by BCG against leprosy and tuberculosis. The study involved 69 newly diagnosed leprosy cases, 238 age-, sex- and neighborhood-matched controls, and 144 newly diagnosed, sputum-smear-positive tuberculosis cases along with 432 age-, sex- and neighborhood-matched controls. Information on BCG vaccination history was inferred from scars. Using matched analysis, the protection imparted by BCG against leprosy was estimated to be 81% [95% confidence interval (CI) = 67-90] with no apparent difference in protection against paucibacillary [vaccine efficacy (VE) = 83%, 95% CI = 58-92] and multibacillary leprosy (VE = 76%; 95% CI = 30-91). The effectiveness against tuberculosis was appreciably lower (VE = 22%) and was not statistically significant (95% CI = -20-51).

Adolescent↗

Evaluation of lymphocyte proliferation assay to purified protein derivative, enzyme linked immunosorbant assay, and tuberculin hypersensitivity in Eales' disease.

The purpose of this study was to evaluate the immunological responses against mycobacterial antigens in Eales' disease. Fifty six patients with Eales' disease and fifty age-and-sex-matched healthy volunteers with normal fundus findings taken as controls, were subjected to Mantoux test, using 2 TU/0.1 ml of purified protein derivative (PPD), lymphocyte proliferation assay to PPD, and ELISA to detect IgM and IgG antibodies against mycobacterial A-60 antigen. The results of Mantoux test and lymphocytes proliferation assay did not differ significantly in the two groups suggesting a similar cellular immune response. The number of individuals with recent exposure/reexposure to tuberculosis (IgM+) was significantly higher among patients. However the number of people with past exposure (IgM-IgG+) was significantly higher among controls. Our study indicates that there are no statistically significant differences in the humoral and cellular immune responses to mycobacterial antigens between the patients with Eales' disease and controls, except for a significantly higher IgM positivity among the patients.

Adolescent↗

Nitric oxide modulates interleukin-1beta and tumour necrosis factor-alpha synthesis, and disease regression by alveolar macrophages in pulmonary tuberculosis.

Pretreatment with nitric oxide synthase (NOS) inhibitors profoundly increases mortality, bacterial burden and pathological tissue damage in mice infected with Mycobacterium tuberculosis. Nitric oxide (NO) production is enhanced in alveolar macrophages (AM) of tuberculosis (TB) patients. Interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha released from AM are involved in the immune response to mycobacterial infection. The aim of the present study was to examine whether NO is implicated in IL-1beta and TNF-alpha synthesis by AM and related to the resolution of disease activity in TB patients. Purified AM were retrieved by bronchoalveolar lavage from TB patients and normal subjects, and cultured in the presence or absence of a NO inhibitor, NG-monomethyl-L-arginine (L-NMMA). The release of IL-1beta and TNF-alpha, and their mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA) and northern analysis, respectively. The level of nitrite released into the culture medium was determined. The rate of disease regression was evaluated by serial chest radiography. The release of nitrite, IL-1beta and TNF-alpha was much greater from AM of TB patients than normal subjects. NG-monomethyl-L-arginine inhibited the production of nitrite as well as IL-1beta and TNF-alpha in TB patients. The mRNA expression for IL-1beta and TNF-alpha was upregulated in TB patients and was depressed by L-NMMA. Immunocytochemistry using a monoclonal antibody against nuclear factor-kappaB (NF-kappaB) subunit p65 showed NF-kappaB was highly expressed and translocated to the nuclei of AM in TB patients, and was inhibited by L-NMMA. An inhibition of NF-kappaB by pyrrolidine dithiocarbamate attenuated IL-1beta and TNF-alpha synthesis. More generation of NO from cultured AM increased the disease regression in TB patients. We conclude that the enhanced NO generation by AM of TB patients may play an autoregulatory role in amplifying the synthesis of pro-inflammatory cytokines, probably through the activation of NF-kappaB. Nitric oxide may also play an important role in resistance to M. tuberculosis infection.

Bronchoalveolar Lavage Fluid↗

[Tuberculosis control and strategy as an urban problem].

Tuberculosis is always an urban problem. There are differences in the severity of pulmonary tuberculosis in relation to socio-economic groups. The percentages of cases shown to be positive by smear microscopy of acid-fast bacilli in their sputum specimens and of cases with cavitary lesions in the lungs were high for the lower socio-economic group. The percentage of cases having had chest X-ray examination within the preceding year was low for the lower socioeconomic group. The Osaka metropolitan area consists of many prefectures and cities. Osaka City is in the center of this great metropolis. Registered cases of each zone had statistically differences about social characteristics. This result was thought to reflect the population of each zone. Cooperative common political will against tuberculosis in this area is needed to promote tuberculosis control. We analyzed the incidence rate in Osaka City in five-year from 1978 to 1997. Until the first half of 1980, the tuberculosis incidence rate in Osaka City had been dropping every year, but the rate of decline has been slowed substantially or even stopped since 1983. The slowdown in the reduction of the tuberculosis incidence rate has occurred not in all wards, but in a few wards and it is a typical phenomenon of the middle-aged in those wards. Such tuberculosis among employees in an insecure position has a growing urban social problem. It is important to establish the cooperation between medical facilities and public health centers within the territory of tuberculosis hospitals in an urban area. The sources of tuberculosis infection in an urban area are quite diverse and complicated. We shall utilize a molecular epidemiologic analysis of Mycobacterium tuberculosis.

Adolescent↗

Biomass cooking fuels and prevalence of tuberculosis in India.

OBJECTIVES: To examine the relation between use of biomass cooking fuels (wood or dung) and prevalence of active tuberculosis in India. METHODS: The analysis is based on 260,162 persons age 20 and over in India's 1992-93 National Family Health Survey. Logistic regression is used to estimate the effects of biomass fuel use on prevalence of active tuberculosis, as reported by household heads, after controlling for a number of potentially confounding variables. RESULTS: Persons living in households that primarily use biomass for cooking fuel have substantially higher prevalence of active tuberculosis than persons living in households that use cleaner fuels (odds ratio [OR] = 3.56; 95% confidence interval [CI] = 2.82-4. 50). This effect is reduced somewhat when availability of a separate kitchen, house type, indoor crowding, age, gender, urban or rural residence, education, religion, caste or tribe, and geographic region are statistically controlled (OR = 2.58; 95% CI = 1.98-3.37). Fuel type also has a large effect when the analysis is done separately for men (OR = 2.46; 95% CI = 1.79-3.39) and women (OR = 2. 74; 95% CI = 1.86-4.05) and separately for urban areas (OR = 2.29; 95% CI = 1.61-3.23) and rural areas (OR = 2.65; 95% CI = 1.74-4.03). The analysis also indicates that, among persons age 20 years and over, 51% of the prevalence of active tuberculosis is attributable to cooking smoke. CONCLUSIONS: Results strongly suggest that use of biomass fuels for cooking substantially increases the risk of tuberculosis in India.

Adult↗

Fluoroquinolones for treating tuberculosis.

BACKGROUND: Fluoroquinolones are sometimes used to treat multiple-drug-resistant and drug-sensitive tuberculosis. The effects of fluoroquinolones in tuberculosis regimens need to be assessed. OBJECTIVES: To assess fluoroquinolones as additional or substitute components to antituberculous drug regimens for drug-sensitive and drug-resistant tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1940 to April 2005), and Russian database (1988 to April 2005). We also scanned reference lists of all identified studies and contacted researchers. SELECTION CRITERIA: Randomized controlled trials of antituberculous regimens containing fluoroquinolones in people diagnosed with bacteriologically positive (sputum smear or culture) pulmonary tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria, assessed methodological quality, and extracted data. We used relative risk (RR) for dichotomous data, weighted mean difference (WMD) for continuous data (both with 95% confidence intervals (CI)), and the random-effects model if we detected heterogeneity and appropriate to combine data. MAIN RESULTS: Ten trials (1178 participants) met the inclusion criteria. No statistically significant difference was found in trials substituting ciprofloxacin or ofloxacin for first-line drugs in relation to cure (89 participants, 2 trials), treatment failure (388 participants, 3 trials), or clinical or radiological improvement (216 participants, 2 trials). Substituting ciprofloxacin into first-line regimens in drug-sensitive tuberculosis led to a higher incidence of relapse (RR 7.17, 95% CI 1.33 to 38.58; 384 participants, 3 trials) and longer time to sputum culture conversion (WMD 0.50 months, 95% CI 0.18 to 0.82; 168 participants, 1 trial), although this was confined to HIV-positive participants. Adding or substituting levofloxacin to basic regimens in drug-resistant areas had no effect. A comparison of sparfloxacin versus ofloxacin added to regimens showed no statistically significant difference in cure (184 participants, 2 trials), treatment failure (149 participants, 2 trials), or total number of adverse events (253 participants, 3 trials). AUTHORS' CONCLUSIONS: Only ciprofloxacin, ofloxacin, levofloxacin, and sparfloxacin have been tested in randomized controlled trials for treating tuberculosis. We cannot recommend ciprofloxacin in treating tuberculosis. Trials of newer fluoroquinolones for treating tuberculosis are needed. No difference has been demonstrated between sparfloxacin and ofloxacin in drug-resistant tuberculosis.

Antitubercular Agents↗

Serum immunoglobulin levels in patients with active pulmonary tuberculosis and patients with Klebsiella infection.

Serum immunoglobulins levels were determined in 42 patients with active pulmonary tuberculosis as a prototype of chronic infection and 41 patients with Klebsiella infection representing acute infection, using a radial immunodiffusion technique. The mean serum concentration of IgG, IgA and IgM of the patients with pulmonary tuberculosis (1980 +/- 688, 314 +/- 152 and 222 +/- 123 mg/dl, respectively) were found to be significantly higher than normal control levels (P less than 0.005). The mean serum IgG, IgA and IgM concentration of the patients with Klebsiella infection (1102 +/- 340, 287 +/- 133 and 168 +/- 105 mg/dl, respectively), were also higher than normal levels but only IgM level differed significantly from the normal control levels (P less than 0.05). The difference in serum IgG and IgM between the patients with pulmonary tuberculosis and Klebsiella infection was statistically significant (P less than 0.05 and P less than 0.05, respectively). These findings reflect the polyclonal hypergammaglobulinemia found in chronic infections, on the one hand, and the rise of IgM of the primary immune response in acute infection, on the other.

Acute Disease↗

Prevalence of HIV-1 and oral lesions in pregnant women in rural Malawi.

OBJECTIVE: Whether oral lesions were associated with human immunodeficiency virus-type 1 (HIV-1) status in a cohort of pregnant Malawian women was studied. STUDY DESIGN: Six hundred thirty-eight women participated in a randomized prospective study at 3 prenatal clinics in a rural area of southern Malawi. Oral examinations, followed by collection of oral fluid specimens with an HIV-1 oral specimen collection device, were performed. The specimens were tested for antibodies against HIV-1. RESULTS: Sixty-one oral lesions were found in 60 participants. While traditional HIV-1 associated lesions were rare, benign migratory glossitis was unexpectedly common (6%). Oral hairy leukoplakia was significantly more common among women who were HIV-1 positive than among women who were HIV-1 negative. An HIV-1 prevalence rate of 21.8% was estimated among the women, with the highest rate of HIV-1 infection (34.1%) among women aged 25 to 29 years. CONCLUSION: Stratifying lesions showed a small number of oral hairy leukoplakia to be markers for HIV-1. A high seroprevalence was found in this rural cohort, but there were unexpectedly few oral lesions. The relatively few oral lesions diagnosed may indicate a recent infection with HIV.

Adult↗

Use of DNA fingerprinting to assess tuberculosis infection control.

BACKGROUND: DNA fingerprinting establishes the genetic relatedness of Mycobacterium tuberculosis isolates and has become a powerful tool in tuberculosis epidemiology. OBJECTIVE: To use DNA fingerprinting to assess the efficacy of current tuberculosis infection-control practices. DESIGN: Retrospective molecular and descriptive epidemiologic study. SETTING: A 700-bed urban public hospital that follows the Centers for Disease Control and Prevention (CDC) guidelines for tuberculosis infection control. PATIENTS: 183 patients who had positive cultures for M. tuberculosis from 1 April 1995 to 31 March 1996. RESULTS: 173 of 183 M. tuberculosis isolates from the study period underwent DNA fingerprinting. Fingerprinting revealed that five isolates represented false-positive cultures and that 91 (54%) of the remaining 168 isolates were in 15 DNA fingerprinting clusters, which ranged in size from 2 to 29 isolates. Risk factors for clustering were birth in the United States, African-American ethnicity, homelessness, substance abuse, and male sex. Retrospective epidemiologic analysis of inpatient and outpatient visits by the 91 patients who had clustered isolates revealed only one possible instance of patient-to-patient transmission. CONCLUSIONS: The DNA fingerprinting of all M. tuberculosis isolates from a 1-year period revealed one possible instance of nosocomial transmission and five false-positive M. tuberculosis cultures. However, these results did not lead to changes in infection-control practices or in clinical care. The study findings do not support the use of DNA fingerprinting for nosocomial tuberculosis surveillance, but they suggest that compliance with the CDC tuberculosis infection-control guidelines may control patient-to-patient transmission in high-risk urban hospitals.

Chicago↗

A novel method for evaluating the antimicrobial activity of tuberculosis treatment regimens.

OBJECTIVE: To evaluate the clinical response to antituberculosis chemotherapy rapidly. METHOD: Sputum viable counts from a previously published clinical trial comparing a standard regimen and one containing isoniazid, rifampicin and ciprofloxacin were re-evaluated using an exponential decay model. The results were fitted to a one or two phase exponential decline. The decline in viable counts followed a curve described by a single-phase exponential decay model. From these data the time taken to reduce the viable count by 50% (vt50) was calculated to estimate the bactericidal effect of the regimens. RESULTS AND CONCLUSION: This method shows promise as a means for early identification of patients who are responding poorly as a result of resistance or poor immune response and for comparing anti-tuberculosis regimens in clinical trials. The failure to show a two-phase exponential decay curve suggested that either the sputum does not contain bacteria upon which only drugs with a sterilising activity act or that they are not present in sufficient numbers to have a significant impact on the total viable count. Further studies are required to understand the physiological state of organisms being sampled in sputum.

Antitubercular Agents↗

Can the poor adhere? Incentives for adherence to TB prevention in homeless adults.

SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.

Adult↗

A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users.

Substance abuse is associated with high risk for tuberculosis (TB) and poor adherence to medication regimens. This study compared completion rates for isoniazid (INH) preventive therapy for injection drug users (IDUs) randomly assigned to methadone treatment combined with directly observed preventive treatment (DOPT) versus those assigned to routine TB clinic referral without methadone treatment. One hundred and eleven opioid-dependent patients with latent TB were assigned to one of three 6-month treatment conditions: standard methadone treatment including substance abuse counseling combined with daily INH DOPT (n=37); minimal methadone treatment without counseling, also combined with daily INH DOPT (n=35); or routine care referral to TB clinic for monthly INH supplies without DOPT and without methadone treatment (n=39). INH completion rates were 77.1% for minimal methadone and 59.5% for standard methadone, as compared with only 13.5% for routine care (P<0.0001). Mean duration of INH treatment retention was 5.7, 5.0 and 1.6 months, respectively (P<0.0001). TB incidence at 4-year follow-up was 0 of 54 subjects who completed preventive therapy versus 2 of 57 who failed to complete. One of these two had been assigned to routine care, and the other to minimal methadone. In conclusion, INH retention time and completion rates were significantly improved by methadone treatment combined with observed INH, whether or not substance abuse counseling was provided. The results of this study indicate that methadone treatment offers clear public health benefits when it is used to deliver preventive medical services.

Adult↗