Tuberculosis In HIV-infected Adults Research Articles

Household air pollution and risk of pulmonary tuberculosis in HIV-Infected adults

BackgroundIn low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection.MethodsWe conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 – March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB.ResultsWe recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm].ConclusionTime spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.

Clinical-paraclinical characteristics of pulmonary tuberculosis associated with human immunodeficiency virus

Clinical-paraclinical characteristics of pulmonary tuberculosis associated with human immunodeficiency virus. Materials and methods: The analysis of selected scientific publications from the HINARI, MEDLINE, EMBASE, etc. Results and conclusions: in recent years, in the world, tuberculosis associated with the human immunodeficiency virus is one of the most serious public health problems, contributing to the increase in cases of morbidity, incapacity for work and mortality. Usually, the disease develops in young people, with the asocial lifestyle, with compromised immunity, etc. The most common manifestation of tuberculosis in HIV-infected adults is pulmonary. Initially, the tuberculous process affects the upper lungs, where cavities, fibrosis, shrinkage and calcification of the lung can occur. When the immunodeficiency increases, the cough becomes rarer, the intrathoracic lymph nodes become lysed more frequently, and the process already affects the lower lung lobes. To prevent tuberculosis in this contingent of patients it is necessary to dispense them with the necessary examination twice a year, indicating timely antiretroviral therapy and chemoprophylaxis.

Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults

BackgroundIn regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death.MethodsWe conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization.ResultsA total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment.ConclusionsAmong severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.)

Predictors of the Occurrence of Tuberculosis in HIV-infected Adults during the First Six Months of Antiretroviral Therapy in Kisangani, DR Congo

Objective: To determine the predictive factors for the occurrence of tuberculosis (TB) in adults infected with the human immunodeficiency virus (HIV) during the first 6 months of antiretroviral therapy (ART) in Kisangani.&#x0D; Methods: A case-control study was carried out during the period from January 1, 2017 to December 31, 2018. Clinical data were collected retrospectively from patients receiving antiretroviral therapy in the city of Kisangani. Of a total of 1,161 HIV-infected patients included in this study, 58 of them developed TB. The diagnosis of tuberculosis was made on the presence of Acid-Alcohol-Resistant Bacile (BAAR) on at least one biological sample or on the basis of a bundle of clinical and paraclinical arguments. This test is done during the first six months of initiating anti retroviral therapy (ART). Predictive factors for the onset of TB in these patients on antiretroviral therapy were identified using logistic regression analysis.&#x0D; Results: After multivariate analysis, the independent factors associated with the onset of TB were: being married (OR = 4.456; 95% CI: 1.061-18.713), residence in the town of Tshopo (OR = 7.04; 95% CI: 1.168-42.47) as well as stages 3 and 4 of AIDS disease (OR = 29 95% CI: 4.563-184.872 and OR = 50.8 95% CI: 3.971-680.995).&#x0D; Conclusion: The results found by this study highlight the need for active TB testing in HIV-infected individuals. Particular emphasis should be placed on the category of patients on antiretroviral therapy who have one of the independent factors for the onset of TB.

Incidence of tuberculosis in HIV-infected adults on first- and second-line antiretroviral therapy in India

BackgroundProgrammatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India.MethodsWe estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India.Results4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86–5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01–2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02–1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13–2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58–5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen.ConclusionRisk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.

Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study

BackgroundVarious individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB).MethodsWithin a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis).ResultsIn the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17–1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26–0.87).ConclusionFactors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

Lateral Flow Urine Lipoarabinomannan Assay (LF-LAM) for Diagnosis of Active Tuberculosis in HIV-Infected Adults: a Prospective Cohort Study

BackgroundEarly diagnosis and treatment of active tuberculosis (TB) in HIV-positive patients is challenging. Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care tests for TB. However, limited data exists on their performance among HIV-TB co-infected patients from Southeast Asian countries.MethodsWe prospectively recruited HIV-positive adult patients with CD4 count less than or equal to 200/mm3 and symptoms suspected of active TB from two tertiary hospitals between December 2015 and March 2017. Freshly collected urine was applied to the Determine®-TB LAM Ag test strip (4 bands of graded intensity), using grade 1 cutoff. Diagnostic accuracy of urine LAM strip test were assessed against microbiological reference standard, defined as positive Mycobacterium tuberculosis cultured from one or more clinical specimens (definite TB) or composite reference standard including definite TB and probable TB, defined as those have symptoms consistent with TB and response to anti-TB treatment.ResultsA total of 280 patients were enrolled. Of whom, 72 (25.7%) and 65 (23.2%) had definite and probable TB. Amongst those with definite TB, LF-LAM test gave a sensitivity of 75.0% (95% CI 63.9–83.6), specificity of 86.0% (95% CI 79.4–90.8) and accuracy of 82.3% (95% CI 76.7–86.8). When compared with the composite reference standard, the test yielded a lower sensitivity (61.3%, 95% CI 53.0–69.1) and accuracy (73.9%, 95% CI 68.5–78.7), with equal specificity. The test showed the highest sensitivity (90.5%, 95% CI 77.9–96.2) and accuracy (85.9%, 95% CI 79.2–90.7) but lower specificity (84.0%, 95% CI 75.6–89.9) in HIV-infected patients with CD4 count less than 50/mm3. The sensitivity of the combined LF-LAM or sputum microscopy was higher than that of either test alone (86.1% vs. 75.0%, 61.1%, respectively). Mycobacterium avium complex (MAC) was cultured in 7 out of 20 with false positive result. Urine LAM strip test can remain positive for up to 4 weeks even after anti-TB treatment.ConclusionUrine LAM assay gave the best performance for diagnosis of active TB in advanced HIV-infected patients and provide an additional benefit of a greater simplicity, speed, with a more easily obtainable sample.Disclosures All authors: No reported disclosures.

Tuberculosis and HIV coinfection in Europe

Objective:To better understand the epidemiology of tuberculosis (TB)/HIV coinfection in the European Union (EU) and European Economic Area (EEA) for planning of prevention and control measures.Design:Analysis of surveillance data.Methods:We performed an analysis of the 2014 TB and AIDS data to assess the burden of TB/HIV coinfection and we applied multivariable logistic regression to evaluate predictors for coinfection.Results:Twenty-one of 31 EU/EEA countries reported HIV testing results for 64.6% of the 32 892 notified TB cases. Of those, 1051 (4.9%) were reported as HIV-positive. Males [adjusted odds ratio (aOR) 1.25; 95% confidence interval (CI) 1.07–1.46] and those in age group 25–44 years were more frequently coinfected. TB cases originating from the WHO African region had the highest proportion of coinfection (aOR 3.28 versus origin in EU/EEA; 95% CI 2.35–4.57). TB treatment was completed successfully by 57.9% of HIV-positive TB cases and 83.5% of HIV-negative cases. In 2014, 3863 cases of AIDS were reported by 29 EU/EEA countries; 691 (17.9%) of these cases presented with TB as an AIDS-defining illness. Persons who had acquired HIV through injecting drug use had higher odds of TB as an AIDS-defining illness (aOR 1.78 versus heterosexual route of transmission; 95% CI 1.37–2.32).Conclusion:TB/HIV coinfection is a substantial problem in the EU/EEA. The occurrence of TB in HIV-positive cases and the low TB treatment success rate suggest that international guidelines for prevention and treatment of TB in HIV-infected adults need to be better implemented.

Determinants for tuberculosis in HIV-infected adults in Northwest Ethiopia: a multicentre case–control study

ObjectiveThe objective of this study was to identify determinants for tuberculosis (TB) among HIV-infected adults in Northwest Ethiopia.DesignCase–control study.SettingThree hospitals and 10 health centres in Northwest Ethiopia.ParticipantsA total of 446...

Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy.

The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy

The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomized controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

Serial testing of interferon-gamma release assay for diagnosis of tuberculosis in HIV-infected adults

Serial testing of interferon-gamma release assay for diagnosis of tuberculosis in HIV-infected adults

Quantiferon-TB Gold: performance for ruling out active tuberculosis in HIV-infected adults with high CD4 count in Côte d'Ivoire, West Africa.

ObjectiveTo assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT).MethodsTransversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml.ResultsAmong the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion.ConclusionA negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases.Trial RegistrationClinicalTrials.gov NCT00495651.

Asymptomatic HIV-infected individuals on antiretroviral therapy exhibit impaired lung CD4(+) T-cell responses to mycobacteria.

HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4(+) T-cell responses observed in HIV-infected ART-naive adults. To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4(+) T-cell responses to Mycobacterium in HIV-infected individuals. Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4(+) T-cell responses were measured by intracellular cytokine staining. HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4(+) T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4(+) T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4(+) T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4(+) T-cell responses were impaired in adults on ART irrespective of duration. AM and mycobacteria-specific alveolar CD4(+) T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated.

A Clinical Scoring Algorithm for Determination of the Risk of Tuberculosis in HIV-Infected Adults: A Cohort Study Performed at Ethiopian Health Centers.

The World Health Organization (WHO) tuberculosis (TB) symptom screening instrument (WHO-TB) can identify human immunodeficiency virus (HIV)-infected individuals at low risk of tuberculosis (TB); however, many patients report WHO-TB symptoms and require further TB investigations. We hypothesized that further clinical scoring could classify subjects with a positive WHO-TB screening result (WHO-TB(+)) for the likelihood of TB. HIV-infected adults eligible to initiate antiretroviral therapy (ART) were recruited and prospectively followed at 5 Ethiopian health centers. Irrespective of symptoms, all participants underwent sputum bacteriological testing for TB. Symptoms, physical findings, hemoglobin, and CD4 cell count results were compared between subjects with and those without bacteriologically confirmed TB. Variables associated with TB in WHO-TB(+) individuals were used to construct a scoring algorithm with multiple logistic regression analysis. Among 812 participants, 137 (16.9%) had TB. One hundred fifty-nine persons (20%) had a negative WHO-TB screen, 10 of whom had TB (negative predictive value [NPV], 94% [95% confidence interval {CI}, 90%-97.5%]). For WHO-TB(+) subjects, the following variables were independently associated with TB, and were assigned 1 point each in the clinical scoring algorithm: cough, Karnofsky score ≤80, mid-upper arm circumference <20 cm, lymphadenopathy, and hemoglobin <10 g/dL. Among subjects with 0-1 points, 20 of 255 had TB (NPV, 92% [95% CI, 89%-95%]), vs 19 of 34 participants with ≥4 points (positive predictive value, 56% [95% CI, 39%-73%]). The use of WHO-TB alone identified 159 of 784 (20%) with a low risk of TB, vs 414 of 784 (53%) using WHO-TB followed by clinical scoring (P< .001). The difference in proportions of confirmed TB in these subsets was nonsignificant (6.3% vs 7.2%; P= .69). Clinical scoring can further classify HIV-infected adults with positive WHO-TB screen to assess the risk of TB, and would reduce the number of patients in need of further TB investigations before starting ART. NCT01433796.

Diagnostic Accuracy of a Rapid Urine Lipoarabinomannan Test for Tuberculosis in HIV-Infected Adults

In settings of high HIV prevalence, tuberculosis control and patient management are hindered by lack of accurate, rapid tuberculosis diagnostic tests that can be performed at point-of-care. The Determine TB LAM Ag (TB LAM) test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis. Prospective diagnostic accuracy study. Hospital and outpatient settings in Uganda and South Africa. HIV-infected adults with tuberculosis symptoms and/or signs. Participants provided a fresh urine specimen for TB LAM testing, blood for mycobacterial culture, and 2 respiratory specimens for smear microscopy and mycobacterial culture. For the TB LAM test, sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis. A total of 1013 participants were enrolled. Among culture-positive tuberculosis patients, the TB LAM test identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4 ≤100 cells per cubic millimeter. The test was specific in 559/573 (97.6%) patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with CD4 ≤100. CD4 ≤50 [adjusted odds ratio (AOR), 6.2; P < 0.001] or 51-100 (AOR, 7.1; P < 0.001), mycobacteremia (AOR, 6.1; P < 0.01) and hospitalization (AOR, 2.6; P = 0.03) were independently associated with a positive TB LAM test. In HIV-positive adults with CD4 ≤100, the TB LAM urine test detected over half of culture-positive tuberculosis patients, in <30 minutes and without the need for equipment or reagents.

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253

To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm(3). Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2-4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22-48) and the specificity 85% (95%CI 81-88). We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding.

Incidence and clinical forms of tuberculosis in HIV infected adults: 2013 versus 2007

Tuberculosis (TB), yet an endemic disease in Romania with a high prevalence compared to the average European incidence, had a slight descendent curve. But in the last 3 years we noticed a new phenomenon: an epidemic of tuberculosis among newly HIV infected intravenous drug users (IVDU). Objective: to determine the incidence, clinical and epidemiological characteristics of the new TB cases and TB reactivation in two different years, 2007 and 2013 (before and after HIV epidemic in IVDU) in our clinic of HIV infected adults. We found a higher incidence of new infected TB cases or TB reactivation in 2013 (45 cases) versus 22 cases in 2007. The average age of patients was lower (33.6 years) in 2013 than in 2007 (35.6). Predominance of male patients was higher in 2013 (79%) vs. 76% in 2007. HIV transmission in 2013: 61% IVDU, 35% sexual transmission, 2% horizontal transmission cohort; in 2007 74% sexually transmitted infection, 14% horizontal infections. In 2013, 41% of HIV-TB coinfected patients were romani ethnics (81% of them IVDU) versus 5% in 2007. The localization of TB infection was comparable in 2013/2007: disseminated TB 46% vs. 51%, pulmonary TB 51% vs. 50%, peripheral adenopathy 1 case each year. In 2007 we had 47% patients with sensibility to the 2 major first class drugs – hydrazine (H) and rifampin (R), resistance to H 6%, to R 12%, MDR 6%. In 2013 we have 85% patients HR-sensitive, 3% H-resistant, 3% R-resistant and 10% MDR. The global mortality of the two groups of patients was higher in 2007 than in 2013 (32% vs. 23%). Deaths related to TB infection were higher in 2013 than in 2007 (89% vs. 57%). Many cases of TB in IVDU HIV infected patients were severe: (58% disseminated TB). Mortality among HIV-TB coinfected IVDU was 50%, versus 8% in non-IVDU patients. TB had a high prevalence in HIV patients, in 2013 as in 2007, involving significant mortality and morbidity. A lot of newly HIV infected persons are still late and very late presenters. We are expecting that the epidemic of ethnobotanic drugs will raise the prevalence of TB. New techniques of TB antibiogram can reduce mortality.

Validating a scoring system for the diagnosis of smear-negative pulmonary tuberculosis in HIV-infected adults.

BackgroundThe challenge of diagnosing smear-negative pulmonary TB (tuberculosis) in people living with HIV justifies the use of instruments other than the smear test for diagnosing the disease. Considering the clinical-radiological similarities of TB amongst HIV-infected adults and children, the proposal of this study was to assess the accuracy of a scoring system used to diagnose smear-negative pulmonary TB in children and adolescents, in HIV-infected adults suspected of having smear-negative pulmonary TB.MethodsA Phase III validation study aiming to assess the diagnostic accuracy of a scoring system for diagnosing smear-negative pulmonary TB in HIV-infected adults. The study assessed sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values of the scoring system. Three versions of the scoring system were tested.ResultsFrom a cohort of 2,382 (HIV-infected adults), 1276 were investigated and 128 were diagnosed with pulmonary TB. Variables associated with the diagnosis of TB were: coughing, weight loss, fever, malnutrition, chest X-ray, and positive tuberculin test. The best diagnostic performance occurred with the scoring system with new scores, with sensitivity = 81.2% (95%-CI 74.5% –88%), specificity = 78% (75.6% –80.4%), PPV = 29.2% (24.5% –33.9%) and NPV = 97.4% (96.4% –98.4%), LR+ = 3.7 (3.4–4.0) and LR− = 0.24 (0.2–0.4).ConclusionThe proposed scoring system (with new scores) presented a good capacity for discriminating patients who did not have pulmonary TB, in the studied population. Further studies are necessary in order to validate it, thus permitting the assessment of its use in diagnosing smear-negative pulmonary TB in HIV-infected adults.

Isoniazid preventive therapy for tuberculosis in South Africa: an assessment of the local evidence base.

Worldwide, South Africa (SA) has the worst tuberculosis (TB) epidemic. In SA, there are > 6.1 million people living with HIV (PLWH) and the country now has the largest antiretroviral treatment programme with > 2 million people receiving combination therapy. While there has been a marked recent decline in HIV-associated deaths, > 50% of TB cases still continue to be diagnosed in PWLH. The current TB control strategy based on passive case finding, chemotherapy of childhood TB contacts and directly observed therapy has clearly failed to control endemic TB in SA. Two recent meta-analyses have shown a > 60% reduction in TB in HIV-infected adults after isoniazid preventive therapy (IPT). SA has implemented the World Health Organization policy and IPT is now recommended for HIV-positive people for up to 36 months. Originally, there was only one SA study included in the evidence base supporting this policy, but subsequently four randomised controlled trials have been conducted in SA populations. These studies, together with local observational studies, are the subject of this local, evidence-based review.