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Diagnosis & treatment of tuberculosis in HIV co-infected patients.

ABSTRACT: Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection.

SUBMITTER: Padmapriyadarsini C

PROVIDER: S-EPMC3284094 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

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Diagnosis & treatment of tuberculosis in HIV co-infected patients.

Padmapriyadarsini C C Narendran G G Swaminathan Soumya S

The Indian journal of medical research 20111201 6

Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor perfo ...[more]

PMID: 22310818

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Project description:Worldwide, about 11% of Tuberculosis (TB) cases occur in people living with HIV (PLHIV) and it is the leading cause of death in this population. An important step towards reducing the incidence and mortality of TB in PLHIV is to reduce the time from onset of symptoms to treatment. Factors related to TB treatment delay therefore need to be understood.Using data from a prospective cohort study of patients diagnosed with TB at the National Institute of Infectious Disease, at the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil we conducted a survival analysis to identify factors associated with patient and health care treatment delay. In our analysis we included patients who were co-infected with TB and HIV (n = 201). Patients were followed during the course of their TB treatment and information regarding duration of symptoms, sociodemographics and clinical characteristics were collected at the baseline visit.The median time from onset of initial symptoms to prescription of TB treatment (total delay) was 82 days. From initiation of symptoms to first visit at INI clinic (patient delay), the median was 51 days. From first visit to initiation of treatment (health care delay) the median was 16 days. Illiteracy was associated with greater patient delay [Hazard Ratio (HR) = 2.25, CI 95% 1.29-3.94]. Having had a previous episode of TB (HR = 0.53, CI 95% 0.37-0.74) and being married (HR = 0.71, CI 95% 0.54-0.94) were inversely related to patient delay. Illiteracy was also associated with greater health care delay (HR = 2.83, CI 95% 1.25-5.47) in contrast to high viral load (HR = 0.37, CI 95% 0.24-0.54) and weight loss greater than 10% (HR = 0.54, CI 95% 0.37-0.8), both of which were inversely related to health care delay.This study highlights the existence of factors that lead to greater risk of delayed treatment of TB among patients co-infected with HIV and TB. These include factors that can be assessed through targeted interventions which have implications for improving treatment outcomes and, through reduced duration of infectiousness, reduce the incidence of TB in Brazil.

Project description:There is an urgent need to identify immunological markers of tuberculosis (TB) risk in HIV co-infected individuals. Previously we have shown that TB recurrence in HIV co-infected individuals on ART was associated with markers of systemic inflammation (IL-6, IL1β and IL-1Rα). Here we examined the effect of additional acute inflammation and microbial translocation marker expression on risk of TB recurrence. Stored plasma samples were drawn from the TB Recurrence upon Treatment with HAART (TRuTH) study, in which individuals with previously treated pulmonary TB were screened for recurrence quarterly for up to 4 years. Recurrent TB cases (n = 37) were matched to controls (n = 102) by original trial study arm assignment and ART start date. Additional subsets of HIV infected (n = 41) and HIV uninfected (n = 37) individuals from Improving Recurrence Success (IMPRESS) study were sampled at active TB and post successful treatment completion. Plasma concentrations of soluble adhesion molecules (sMAdCAM, sICAM and sVCAM), lipopolysaccharide binding protein (LBP) and transforming growth factor-beta (TGF-β1, TGF-β2, TGF-β3) were measured by multiplex immunoassays and ELISA. Cytokine data was square root transformed in order to reduce variability. Multivariable analysis adjusted for a number of potential confounders measured at sample time-point: age, BMI, CD4 count, viral load (VL) and measured at baseline: presence or absence of lung cavities, previous history of TB, and WHO disease stage (4 vs 3). The following analytes were associated with increased risk of TB recurrence in the multivariable model: sICAM (aOR 1.06, 95% CI: 1.02-1.12, p = 0.009), LBP (aOR 8.78, 95% CI: 1.23-62.66, p = 0.030) and TGF-β3 (aOR 1.44, 95% CI 1.01-2.05, p = 0.044). Additionally, we observed a positive correlation between LBP and sICAM (r= 0.347, p<0.0001), and LBP and IL-6, identified to be one of the strongest predictors of TB risk in our previous study (r=0.623, p=0.03). These data show that increased risk of TB recurrence in HIV infected individuals on ART is likely associated with HIV mediated translocation of microbial products and the resulting chronic immune activation.

Project description:BACKGROUND:Extra pulmonary manifestation of tuberculosis (TB) accounts for approximately one-half of TB cases in HIV-infected individuals with pleural TB as the second most common location. Even though mycobacteria are cleared, mycobacterial antigens may persist in infected tissues, causing sustained inflammation and chronicity of the disease. The aim of this study was to explore various mycobacterial antigens in pleural effusions, the impact of HIV infection and CD4+ T-cell depletion on the presence of antigens, and the diagnostic potential of antigens for improved and rapid diagnosis of pleural TB. METHODS:Pleural fluid specimens were collected from patients presenting with clinically suspected pleural TB, and processed routinely for culture, cytology, and adenosine deaminase activity analysis. HIV status and CD4+ T-cell counts were recorded. Pleural fluid mononuclear cells (PFMC) were isolated, and cell smears were stained with acid-fast staining and immunocytochemistry for various mycobacterial antigens. Real-time and nested-PCR were performed. Patients were categorized as pleural TB or non-TB cases using a composite reference standard. Performance of the mycobacterial antigens as diagnostic test was assessed. RESULTS:A total of 41 patients were enrolled, of which 32 were classified as pleural TB and 9 as non-TB. Thirteen patients had culture confirmed pleural TB, 26 (81%) were HIV-TB co-infected, and 64% had < 100 CD4+ T-cells/microL. Both secreted and cell-wall mycobacterial antigens were detected in PFMC. Lipoarabinomannan (LAM) was the most frequently detected antigen. There was no direct correlation between positive culture and antigens. Cases with low CD4+ T-cell counts had higher bacterial and antigen burden. By combining detection of secreted antigen or LAM, the sensitivity and specificity to diagnose pleural TB was 56 and 78%, respectively, as compared to 41 and 100% for culture, 53 and 89% for nested PCR, and 6 and 100% for real-time PCR. CONCLUSION:Mycobacterial antigens were detectable in PFMC from tuberculous pleural effusions, even in cases where viable mycobacteria or bacterial DNA were not always detected. Thus, a combination of secreted antigen and LAM detection by immunocytochemistry may be a complement to acid-fast staining and contribute to rapid and accurate diagnosis of pleural TB.

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Diagnosis & treatment of tuberculosis in HIV co-infected patients.

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Diagnosis & treatment of tuberculosis in HIV co-infected patients.

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