Risk Of Incident Tuberculosis Research Articles

Socioeconomic deprivation and tuberculosis in Germany: a longitudinal spatial analysis (2001–2022)

Abstract Background Socioeconomic conditions may affect tuberculosis (TB) dynamics. We analyzed the relation between area-level socioeconomic deprivation and TB incidence in Germany between 2001-2022. Methods Using nationally representative data at the level of 400 German districts, we fitted generalized linear mixed models to assess the effect of socioeconomic deprivation on TB incidence controlling for age, sex, share of non-nationals population, share of refugees, geographic effects, location and time. We estimated crude and adjusted risk ratios (RR) and corresponding 95% Confidence Intervals (95%-CI) for socioeconomic deprivation quintiles (Q1-Q5), ranging from least (Q1) to most deprived (Q5) districts. Results Preliminary findings show that crude TB incidence risk was 7% higher (RR = 1.07, 95%-CI=1.04-1.09) in least (Q1) compared to most deprived areas (Q5). Districts with medium-low (Q2), medium (Q3), and medium-high (Q4) socioeconomic deprivation showed 1% higher (1.01, 0.98-1.03), 4% lower (0.96, 0.94-0.99) and 3% lower (0.97 0.94-1.00) risk, respectively, compared to the most deprived districts (Q5). Fully adjusted incidence risk was 6% lower for Q1 compared to Q5 (0.94, 0.86-1.02), while districts classified in quintiles Q2-Q4 showed 8% (0.92, 0.86-0.99), 6% (0.94, 0.88-1.01) and 3% (0.97, 0.92-1.02) lower risk compared to Q5, respectively. Conclusions The adjusted effect of area-level socioeconomic deprivation on the risk of TB incidence has been low in Germany. Not considering the assumed confounders leads to over-estimation of the association between area-level SES and TB. Future studies should explore further area-level or individual factors in order to better understand the spatial variation of TB incidence in Germany. Key messages • Area-level socioeconomic deprivation has a low effect on the risk of TB incidence across German districts. • Further research is needed in order to better understand the spatial variation of TB incidence in Germany.

Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV.

Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.

Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial.

Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT). This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50cells/μL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes. Of all 269 participants, 76.2% (n=205) were anaemic, and 31.2% (n=84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32-9.76, p=0.012) and death (aOR: 3.63, 95% CI: 1.07-12.33, p=0.039). Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes. National Institutes of Health.

Perspectives of Healthcare Professionals on Factors Limiting Implementation of Isoniazid Preventive Therapy in People Living with HIV in Eritrea: A Qualitative Study.

PurposeIn Eritrea, a 6-month isoniazid preventive therapy (IPT) was introduced in Eritrea in 2014 to prevent/reduce risk of incident tuberculosis in people living with HIV (PLHIV). The global and local uptake of IPT in newly enrolled PLHIV was reported to be low. Anecdotal reports showed that there was resistance from clinicians against its implementation. This study was therefore conducted to explore the factors that affect implementation of IPT in Eritrea from the perspectives of healthcare professionals.Materials and MethodsAn exploratory qualitative study that used a framework content analysis using inductive approach was employed. Data were collected from a sample of HIV care clinic prescribers from regional and national referral hospitals through in-depth interviews. Senior program officers were also interviewed as key informants. A conceptual framework model was developed using a root cause analysis.ResultsOverall, five themes and 13 sub-themes emerged from the in-depth interviews with healthcare professionals and key informants. Several multi-level causes/factors related to the healthcare system, HIV control program, healthcare professionals, patients and the product were identified as barriers to the implementation of IPT. Information gap on IPT and fear of isoniazid-induced liver injury were identified as the main reasons for the reluctance in administering IPT. It was observed that healthcare professionals had significant information gap that resulted in rumors and doubts on the benefits and risks of IPT, which ultimately caused reluctance on its implementation. Inadequate planning and operationalization during the introduction of IPT and inadequate laboratory setups were found to be the possible root causes for the aforementioned central problems.ConclusionThe root causes/factors for the limited implementation of IPT in Eritrea were mainly related to the HIV control program and the healthcare system. Adequate planning, operationalization and capacitation of the existing laboratory setups are recommended for a successful implementation of IPT.

Evaluation of a transcriptomic signature of tuberculosis risk in combination with an interferon gamma release assay: A diagnostic test accuracy study

SummaryBackgroundWe evaluated the diagnostic and prognostic performance of a transcriptomic signature of tuberculosis (TB) risk (RISK11) and QuantiFERON-TB Gold-plus (QFTPlus) as combination biomarkers of TB risk.MethodsHealthy South Africans who were HIV-negative aged 18–60 years with baseline RISK11 and QFTPlus results were evaluated in a prospective cohort study conducted between Sept 20, 2016 and Dec 20, 2019. Prevalence and incidence-rate ratios were used to evaluate risk of TB. Positive (LR+) and negative (LR–) likelihood ratios were used to compare individual tests versus Both-Positive (RISK11+/QFTPlus+) and Either-Positive (RISK11+ or QFTPlus+) combinations.FindingsAmong 2912 participants, prevalent TB in RISK11+/QFTPlus+ participants was 13·3-fold (95% CI 4·2–42·7) higher than RISK11–/QFTPlus–; 2·4–fold (95% CI 1·2–4·8) higher than RISK11+/QFTPlus–; and 4·5-fold (95% CI 2·5–8·0) higher than RISK11–/QFTPlus+ participants. Risk of incident TB in RISK11+/QFTPlus+ participants was 8·3-fold (95% CI 2·5–27·0) higher than RISK11–/QFTPlus–; 2·5-fold (95% CI 1·0–6·6) higher than RISK11+/QFTPlus–; and 2·1-fold (95% CI 1·2–3·4) higher than RISK11–/QFTPlus+ participants, respectively. Compared to QFTPlus, the Both-Positive test combination increased diagnostic LR+ from 1·3 (95% CI 1·2–1·5) to 4·7 (95% CI 3·2–7·0), and prognostic LR+ from 1·4 (95% CI 1·2–1·5) to 2·8 (95% CI 1·5–5·1), but did not improve upon RISK11 alone. Compared with RISK11, the Either-Positive test combination decreased diagnostic LR– from 0·7 (95% CI 0·6–0·9) to 0·3 (95% CI 0·2–0·6), and prognostic LR– from 0·9 (95% CI 0·8–1·0) to 0·3 (0·1–0·7), but did not improve upon QFTPlus alone.InterpretationCombining two tests such as RISK11 and QFTPlus, with discordant individual performance characteristics does not improve overall discriminatory performance, relative to the individual tests.FundingBill and Melinda Gates Foundation, South African Medical Research Council.

Impact of the Relationship between Anaemia and Systemic Inflammation on the Risk of Incident Tuberculosis and Death in Persons with Advanced HIV: A Sub-Analysis of the REMEMBER Trial

Impact of the Relationship between Anaemia and Systemic Inflammation on the Risk of Incident Tuberculosis and Death in Persons with Advanced HIV: A Sub-Analysis of the REMEMBER Trial

Progression of chronic kidney disease and the risk of tuberculosis: an observational cohort study.

<sec id="st1"> <title>BACKGROUND</title> Little is known about tuberculosis (TB) risk in the earlier stages of chronic kidney disease (CKD). </sec> <sec id="st2"> <title>OBJECTIVE</title> To investigate the relationship between CKD at all stages and the risk of incident TB. </sec> <sec id="st3"> <title>METHODS</title> We conducted a cohort study using 100 058 participants of a community-based health screening programme in northern Taiwan, 2005-2008. Renal function was ascertained at baseline using serum creatinine level and the urine dipstick test. The occurrence of active TB was ascertained using the National Tuberculosis Registry. Cox proportional hazards regression was used to estimate the association between CKD and TB. </sec> <sec id="st4"> <title>RESULTS</title> During a median follow-up of 7.5 years, TB incidence was 472. In the Cox regression analyses, individuals with Stage 1-4 CKD had a 25% increase in TB hazard than those without disease (adjusted hazard ratio [aHR] 1.25, 95%CI 1.02-1.54). A positive correlation between CKD stage and TB was observed (P = 0.02 for trend). TB risk increased by 5.1% with every 10 ml/min/1.73 m² decrease in the estimated glomerular filtration rate (aHR 1.05, 95%CI 0.99-1.12). </sec> <sec id="st5"> <title>CONCLUSIONS</title> Our results suggested an increased risk of TB in early-stage CKD. TB prevention efforts should consider individuals with earlier stages of CKD. </sec>.

Association of social deprivation and outdoor air pollution with pulmonary tuberculosis in spatiotemporal analysis

ABSTRACTThe objective of this study was to identify the association between social deprivation, outdoor air pollution, and tuberculosis (TB) incidence rate or mortality rate. The study sample comprised 25 districts in Seoul, Korea. We used two public data derived from the Community Health Survey and Seoul Statistics. The geographic information system analysis and random effects Poisson regression were applied to explore the association of social deprivation and air pollution with TB incidence and mortality. An 1 ppb increase in sulfur dioxide (SO2) concentration was significantly associated with the risk of TB incidence (risk ratio [RR] = 1.046, 95% confidence interval [CI]: 1.028, 1.065). An 1 unit increase in the deprivation index was significantly related to a6% increase in the mortality of TB (RR = 1.063, 95% CI: 1.031, 1.097). : Our results imply that social deprivation and air pollution may affect the different TB outcomes. Effective policy-making for TB control should reflect the differing outcomes between TB incidence and mortality.

The incidence of tuberculosis among hiv-positive individuals with high CD4 counts: implications for policy.

BackgroundIntensified case finding (ICF) and earlier antiretroviral therapy (ART) initiation are strategies to reduce burden of HIV-associated tuberculosis (TB). We describe incidence of and associated factors for TB among HIV-positive individuals with CD4 counts > 350 cells/μl in South Africa.MethodsProspective cohort study of individuals recruited for a TB vaccine trial. Eligible individuals without prevalent TB were followed up at 6 and 12 months after enrolment. Cox proportional hazards regression was used to determine factors associated with risk of incident TB.ResultsSix hundred thirty-four individuals were included in the analysis [80.9 % female, 57.9 % on ART, median CD4 count 562 cells/μl (IQR 466–694 cells/μl)]. TB incidence was 2.7 per 100 person-years (pyrs) (95 % CI 1.6–4.4 per 100 pyrs) and did not differ significantly between those on ART and those not on ART [HR 0.65 (95 % CI 0.24–1.81)]. Low body mass index (BMI <18.5 kg/m2) was associated with incident TB [HR 3.87 (95 % CI 1.09–13.73)]. Half of the cases occurred in the first 6 months of follow up and may have been prevalent or incubating cases at enrolment.ConclusionsTB incidence was high and associated with low BMI. Intensified case finding for TB should be strengthened for all HIV positive individuals regardless of their CD4 count or ART status.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1598-8) contains supplementary material, which is available to authorized users.

Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink.

BackgroundPrevious cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB.We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening.MethodsUsing data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990–2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates.ResultsDuring just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons).ConclusionsDiabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0381-9) contains supplementary material, which is available to authorized users.

Initiating patients on antiretroviral therapy at CD4 cell counts above 200 cells/μl is associated with improved treatment outcomes in South Africa

To compare treatment outcomes by starting CD4 cell counts using data from the Comprehensive International Program of Research on AIDS-South Africa trial. An observational cohort study. Patients presenting to primary care clinics with CD4 cell counts below 350 cells/microl were randomized to either doctor or nurse-managed HIV care and followed for at least 2 years after antiretroviral therapy (ART) initiation. Clinical and laboratory outcomes were compared by baseline CD4 cell counts. Eight hundred and twelve patients were followed for a median of 27.5 months and 36% initiated ART with a CD4 cell count above 200 cells/microl. Although 10% of patients failed virologically, the risk was nearly double among those with a CD4 cell count of 200 cells/microl or less vs. above 200 cells/microl (12.2 vs. 6.8%). Twenty-one deaths occurred, with a five-fold increased risk for the low CD4 cell count group (3.7 vs. 0.7%). After adjustment, those with a CD4 cell count of 200 cells/microl had twice the risk of death/virologic failure [hazard ratio 1.9; 95% confidence interval (CI), 1.1-3.3] and twice the risk of incident tuberculosis (hazard ratio 1.90; 95% CI, 0.89-4.04) as those above 200 cells/microl. Those with either a CD4 cell count of 200 cells/microl or less (hazard ratio 2.1; 95% CI, 1.2-3.8) or a WHO IV condition (hazard ratio 2.9; 95% CI, 0.93-8.8) alone had a two-to-three-fold increased risk of death/virologic failure vs. those with neither, but those with both conditions had a four-fold increased risk (hazard ratio 3.9; 95% CI, 1.9-8.1). We observed some decreased loss to follow-up among those initiating ART at less than 200 cells/microl (hazard ratio 0.79; 95% CI, 0.50-1.25). Patients initiating ART with higher CD4 cell counts had reduced mortality, tuberculosis and less virologic failure than those initiated at lower CD4 cell counts. Our data support increasing CD4 cell count eligibility criteria for ART initiation.

Smoking and Risk of Tuberculosis Incidence, Mortality, and Recurrence in South Korean Men and Women

The authors explored the association of cigarette smoking with tuberculosis incidence, recurrence, and mortality. A 14-year prospective cohort study (1992-2006) was carried out in 1,294,504 South Koreans. Participants were grouped by smoking history, and the authors assessed tuberculosis incidence, mortality, and recurrence risk for each group. Unadjusted and adjusted Cox proportional hazards models were used to investigate the association between smoking history and the 3 outcomes of interest, adjusting for age and alcohol use. Compared with never smokers, current smokers had increased mortality from tuberculosis among both men (adjusted hazard ratio (HR) = 1.6, 95% confidence interval (CI): 1.3, 2.0) and women (HR = 1.6, 95% CI: 1.0, 2.4). Current male smokers had greater risk of incident tuberculosis than former smokers (HR = 1.4, 95% CI: 1.3, 1.5), and risk among current smokers increased with number of cigarettes smoked daily. In females, cigarette smoking was not associated with incident tuberculosis. There was interaction between smoking and sex for incidence (P = 0.00047). The effect of smoking was generally reduced with adjustment for body mass index. Among men, the highest alcohol consumption category (> or =100 g/day) was associated with risk of incident tuberculosis (HR = 1.5, 95% CI: 1.3, 1.7). This study provides longitudinal evidence that smoking increases risk of incident tuberculosis, mortality from tuberculosis, and tuberculosis recurrence.

Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control

To determine burden and risk factors for tuberculosis (TB) in an antiretroviral treatment (ART) programme and its impact on ART outcomes. Prospective cohort study. Prevalent TB was assessed at baseline and incident TB was ascertained prospectively over 3 years among 944 patients accessing a community-based ART programme in South Africa. At enrollment, median CD4 cell count was 96 cells/microl and 52% of patients had a previous history of TB. Prevalent TB (current antituberculosis treatment or active TB) was present in 25% and was strongly associated with advanced immunodeficiency. During 782 person-years of ART, 81 cases of TB were diagnosed. The incidence was 22.1/100 person-years during the first 3 months of ART and decreased to an average of 4.5/100 person-years during the second and third years. In multivariate analysis, risk of incident TB during follow-up was only associated with the current absolute CD4 cell count at that time point; an increase of 100 cells/mul was associated with a 25% lower risk (P = 0.007). Although prevalent and incident TB were associated with greater than two-fold increased mortality risk, they did not compromise immunological and virological outcomes among survivors at 48 weeks. Late initiation of ART was associated with a major burden of TB in this ART programme. TB reduced survival but did not impair immunovirological outcomes. Reductions in TB incidence during ART were dependent on CD4 cell count; however, after 3 years of treatment, rates were still 5- to 10-fold higher than among non-HIV-infected people. Earlier initiation of ART may reduce this burden of TB.