TB-associated Mortality Research Articles

The challenge of minimizing tuberculosis burden in people living with HIV in the Asia Pacific.

The challenge of minimizing tuberculosis burden in people living with HIV in the Asia Pacific.

Early mortality in tuberculosis patients initially lost to follow up following diagnosis in provincial hospitals and primary health care facilities in Western Cape, South Africa.

In South Africa, low tuberculosis (TB) treatment coverage and high TB case fatality remain important challenges. Following TB diagnosis, patients must link with a primary health care (PHC) facility for initiation or continuation of antituberculosis treatment and TB registration. We aimed to evaluate mortality among TB patients who did not link to a TB treatment facility for TB treatment within 30 days of their TB diagnosis, i.e. who were "initial loss to follow-up (ILTFU)" in Cape Town, South Africa. We prospectively included all patients with a routine laboratory or clinical diagnosis of TB made at PHC or hospital level in Khayelitsha and Tygerberg sub-districts in Cape Town, using routine TB data from an integrated provincial health data centre between October 2018 and March 2020. Overall, 74% (10,208/13,736) of TB patients were diagnosed at PHC facilities and ILTFU was 20.0% (2,742/13,736). Of ILTFU patients, 17.1% (468/2,742) died, with 69.7% (326/468) of deaths occurring within 30 days of diagnosis. Most ILTFU deaths (85.5%; 400/468) occurred in patients diagnosed in hospital. Multivariable logistic regression identified increasing age, HIV positive status, and hospital-based TB diagnosis (higher in the absence of TB treatment initiation and being ILTFU) as predictors of mortality. Although hospitals account for a modest proportion of diagnosed TB patients they have high TB-associated mortality. A hospital-based TB diagnosis is a critical opportunity to identify those at high risk of early and overall mortality. Interventions to diagnose TB before hospital admission, improve linkage to TB treatment following diagnosis, and reduce mortality in hospital-diagnosed TB patients should be prioritised.

A retrospective cohort study of early mortality among patients with HIV/TB co-infection in Shanghai municipality.

Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China. Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed. Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90days and 1year of admission, respectively. Of the 64TB-related deaths, 59 (92.2%) occurred within 90days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P<0.001], no antiretroviral therapy (ART) within 3months after admission (OR=11, 95% CI: 6.4-18.9, P<0.001), and plasma albumin level <25g/L (OR=1.91, 95% CI: 1.07-3.40, P=0.021) were associated with early death. Tuberculosis co-infection was prevalent and fatal in HIV-infected patients, with most deaths occurring within 90days of admission. Early mortality was associated with CNS-TB, no ART, and serum albumin level <25g/L.

Estimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda.

IntroductionTuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda.MethodsAt ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU.ResultsOf 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61–6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%-11.6%) to 10.2% (95% CI 7.7%-13.4%).ConclusionPatients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.

Inequality in uptake of isoniazid prevention therapy and Mantoux test among pregnant women with HIV in the Eastern Cape, South Africa

BackgroundHIV-associated tuberculosis (TB) is a major cause of death among pregnant women in South Africa. Isoniazid prevention therapy (IPT) strategy was implemented in South Africa concurrently with life-long antiretroviral therapy (ART) to reduce the TB-associated morbidity and mortality in individuals living with HIV. This study assessed the extent of the implementation of IPT and the performance of the Mantoux test by geographic settings of health facilities and residences of pregnant women living with HIV in the Eastern Cape, South Africa.MethodsWe conducted a data analysis of 1709 pregnant women enrolled in the new electronic database of the prevention of mother-to-child transmission programme of the East London Prospective Cohort Study. Relevant data on place of residence and antenatal care, performance of the Mantoux test and subsequent initiation of IPT were obtained. Descriptive and inferential statistics were employed to analyse the geographical variations and accessibility to Mantoux test and IPT.ResultsThe analysis shows that Mantoux test was performed on 803 pregnant women (47%) with significant geographical variation. After controlling for relevant covariates, pregnant women who resided in rural areas (AOR:0.63; CI: 0.47–0.84) compared to those who resided in urban areas were significantly less likely to receive Mantoux test. The rate of uptake of IPT was 79% with significant geographic variations. In the unadjusted model, rural place of residence (UOR:0.68; CI: 0.49–0.96) was independently associated with lower likelihood of uptake of INH prophylaxis; however, the effect was not significant after controlling for important covariates.ConclusionsThe high uptake rate of isoniazid prevention therapy in pregnant women living with HIV at the study sites is commendable; however, concerted efforts are needed to address the inequality gaps in the roll-out of IPT. Poor performance of Mantoux test is a serious concern and requires the attention of TB programme managers and other relevant authorities.

The Roll-out of Child-friendly Fixed-dose Combination TB Formulations in High-TB-Burden Countries: A Case Study of STEP-TB

Childhood tuberculosis (TB) has hitherto been treated through estimation of pediatric doses through the crushing of adult pills, but the bitter taste of the pills and the inaccuracy of this dosing method presents a challenge for both patients and healthcare providers, leading to poor treatment outcomes. The TB Alliance therefore launched the Speeding Treatments to End Pediatric-Tuberculosis (STEP-TB) project to incentivize the introduction of pediatric Fixed-Dose Combinations (FDCs) of TB drugs. This case study describes the elements of this project, evaluates its impact, and highlights future challenges for pediatric TB treatment. The impact assessment incorporates both market impact as well as projected public health impact, evaluating the availability, affordability, and quality of the FDCs, and lastly providing a projection of lives saved as a result of scale-up of the FDCs to near-universal availability and utilization, based on a publicly available pediatric TB-specific model. STEP-TB resulted in the development of two child-friendly FDCs that were successfully brought to market and made available in 20 of the project’s 22 high-burden countries. On the basis of a country-specific projection of pediatric TB mortality in Kenya, scale-up to near-universal availability and utilization of the new FDCs could reduce pediatric TB-associated mortality by 2660 cases over the next 5 years. Future challenges include maintaining affordable prices for the FDCs and considering mechanisms to incentivize their introduction among high-risk groups in low-burden countries.

Treatment outcomes of drug-resistant tuberculosis in the Netherlands, 2005\u20132015

BackgroundSince in low incidence TB countries population migration and complex treatment of drug-resistant tuberculosis (DR-TB) patients are major issues, we aimed to analyse patient risk factors associated with the incidence of poor outcome of TB treatment among DR-TB patients in the Netherlands.MethodsThis retrospective cohort study included adult patients with confirmed DR-TB treated from 2005 to 2015. We obtained data from a nationwide exhaustive registry of tuberculosis patients in the Netherlands. Predictors for unsuccessful TB treatment (defaulted and failed treatment) and TB-associated mortality were analysed using multivariate logistic regression.ResultsAmong 10,303 registered TB patients, 545 patients with DR-TB were analysed. Six types of DR-TB were identified from the included patients, i.e. isoniazid mono- or poly-resistance (68%); rifampicin mono- or poly-resistance (3.1%); pyrazinamide mono-resistance (8.3%); ethambutol mono-resistance (0.1%); multidrug-resistance (18.9%); and extensively drug-resistance (0.7%). The majority of patients were foreign-born (86%) and newly diagnosed TB (89%) patients. The cumulative incidence of unsuccessful treatment and mortality were 5 and 1%, respectively. Among all DR-TB cases, patients with Multi Drug-Resistant Tuberculosis (MDR-TB) (OR 4.43; 95%CI 1.70–11.60) were more likely to have unsuccessful treatment, while miliary and central nervous system TB (OR 15.60; 95%CI 2.18–111.52) may also be predictors for TB mortality. Additionally, patients with substance abuse and homelessness tend to have unsuccessful treatment.ConclusionsIn recent years, we identified a low incidence of DR-TB as well as the poor outcome of DR-TB treatment. The majority of cases were primary drug-resistant and foreign-born. To further improve treatment outcome, special attention should be given to the high-risk DR-TB patients.

Matrix metalloproteinases: Expression, regulation and role in the immunopathology of tuberculosis.

Mycobacterium tuberculosis (Mtb) leads to approximately 1.5 million human deaths every year. In pulmonary tuberculosis (TB), Mtb must drive host tissue destruction to cause pulmonary cavitation and dissemination in the tissues. Matrix metalloproteinases (MMPs) are endopeptidases capable of degrading all components of pulmonary extracellular matrix (ECM). It is well established that Mtb infection leads to upregulation of MMPs and also causes disturbance in the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thus altering the extracellular matrix deposition. In TB, secretion of MMPs is mainly regulated by NF‐κB, p38 and MAPK signalling pathways. In addition, recent studies have demonstrated the immunomodulatory roles of MMPs in Mtb pathogenesis. Researchers have proposed a new regimen of improved TB treatment by inhibition of MMP activity to hinder matrix destruction and to minimize the TB‐associated morbidity and mortality. The proposed regimen involves adjunctive use of MMP inhibitors such as doxycycline, marimastat and other related drugs along with front‐line anti‐TB drugs to reduce granuloma formation and bacterial load. These findings implicate the possible addition of economical and well‐tolerated MMP inhibitors to current multidrug regimens as an attractive mean to increase the drug potency. Here, we will summarize the recent advancements regarding expression of MMPs in TB, their immunomodulatory role, as well as their potential as therapeutic targets to control the deadly disease.

Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary.

Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children.

Predictors for treatment outcomes among patients with drug-susceptible tuberculosis in the Netherlands: a retrospective cohort study

ObjectivesWe evaluated treatment outcomes and predictors for poor treatment outcomes for tuberculosis (TB) among native- and foreign-born patients with drug-susceptible TB (DSTB) in the Netherlands. MethodsThis retrospective cohort study included adult patients with DSTB treated from 2005 to 2015 from a nationwide exhaustive registry. Predictors for unsuccessful treatment outcomes (default and failure) and TB-associated mortality were analysed using multivariate logistic regression. ResultsAmong 5674 identified cases, the cumulative incidence of unsuccessful treatment and mortality were 2.6% (n/N = 146/5674) and 2.0% (112/5674), respectively. Although most patients were foreign-born (71%; 4042/5674), no significant differences in these outcomes were observed between native- and foreign-born patients (p > 0.05). Significant predictors for unsuccessful treatment were aged 18–24 years (odds ratio (OR), 2.04; 95% CI 1.34–3.10), homelessness (OR, 2.56; 95% CI 1.16–5.63), prisoner status (OR, 5.39; 95% CI 2.90–10.05) and diabetes (OR, 2.02; 95% CI 1.03–3.97). Furthermore, predictors for mortality were aged 74–84 years (OR, 5.58; 95% CI 3.10–10.03) or ≥85 years (OR, 9.35, 95% CI 4.31–20.30), combined pulmonary and extra-pulmonary TB (OR, 4.97; 95% CI 1.42–17.41), central nervous system (OR, 120, 95% CI 34.43–418.54) or miliary TB (OR, 10.73, 95% CI 2.50–46.02), drug addiction (OR, 3.56; 95% CI 1.34–9.47) and renal insufficiency/dialysis (OR, 3.23; 95% CI 1.17–8.96). ConclusionsNative- and foreign-born patients exhibited similar TB treatment outcomes. To further reduce disease transmission and inhibit drug resistance, special attention should be given to high-risk patients.

Tuberculosis in Mozambique: Where Do We Stand?

Tuberculosis (TB) is a global health concern, and Mozambique is one of the few high burden tuberculosis countries where the estimated TB incidence has not improved in recent years. The objective of this review is to provide a snapshot of the current situation of the TB epidemic in Mozambique, highlighting the main epidemiological features and particularities of TB care and control in the country. Despite several efforts aimed at improving diagnosis and treatment success, the overall burden of TB, HIV-TB, and multidrug-resistant (MDR)-TB is enormous, with high TB-associated mortality. Improving surveillance is a key step for understanding the TB epidemic in the country, and the first TB prevalence survey is underway. Overall, drug-sensitive and MDR-TB notifications have increased markedly over the last 5 years, likely due in part to a more active case finding approaches, but the diagnosis gap is still substantial. The roll-out of Xpert technology to decentralized settings is improving TB diagnosis in the country, particularly for MDR-TB. Although some progress has been made in TB control in Mozambique, the challenges for TB control and elimination are enormous. More actively finding cases at health facilities and in communities via contact tracing, improving national surveillance/monitoring and evaluation systems, expanding TB molecular diagnosis, implementing shorter MDR-TB treatments, and improving HIV-TB case management (including rigorous TB screening and higher coverage of preventive therapies in people living with HIV) are considered key priorities for the National TB Control Program.

Incidence and predictors of tuberculosis among HIV-infected adults after initiation of antiretroviral therapy in Nigeria, 2004-2012.

BackgroundNigeria had the most AIDS-related deaths worldwide in 2014 (170,000), and 46% were associated with tuberculosis (TB). Although treatment of people living with HIV (PLHIV) with antiretroviral therapy (ART) reduces TB-associated morbidity and mortality, incident TB can occur while on ART. We estimated incidence and characterized factors associated with TB after ART initiation in Nigeria.MethodsWe analyzed retrospective cohort data from a nationally representative sample of adult patients on ART. Data were abstracted from 3,496 patient records, and analyses were weighted and controlled for a complex survey design. We performed domain analyses on patients without documented TB disease and used a Cox proportional hazard model to assess factors associated with TB incidence after ART.ResultsAt ART initiation, 3,350 patients (95.8%) were not receiving TB treatment. TB incidence after ART initiation was 0.57 per 100 person-years, and significantly higher for patients with CD4<50/μL (adjusted hazard ratio [AHR]: 4.2, 95% confidence interval [CI]: 1.4–12.7) compared with CD4≥200/μL. Patients with suspected but untreated TB at ART initiation and those with a history of prior TB were more likely to develop incident TB (AHR: 12.2, 95% CI: 4.5–33.5 and AHR: 17.6, 95% CI: 3.5–87.9, respectively).ConclusionIncidence of TB among PLHIV after ART initiation was low, and predicted by advanced HIV, prior TB, and suspected but untreated TB. Study results suggest a need for improved TB screening and diagnosis, particularly among high-risk PLHIV initiating ART, and reinforce the benefit of early ART and other TB prevention efforts.

Delay in the Provision of Antiretroviral Therapy to HIV-infected TB Patients in Nigeria.

BackgroundNigeria has a high burden of HIV and tuberculosis (TB). To reduce TB-associated morbidity and mortality, the World Health Organization recommends that HIV-positive TB patients receive antiretroviral therapy (ART) within eight weeks of TB treatment initiation, or within two weeks if profoundly immunosuppressed (CD4<50 cell/μL).MethodsTB and HIV clinical records from facilities in two Nigerian states between October 1st, 2012 and September 30th, 2013 were retrospectively reviewed to assess uptake and timing of ART initiation among HIV-positive TB patients. Healthcare workers were qualitatively interviewed to assess TB/HIV knowledge and barriers to timely ART.ResultsData were abstracted from 4,810 TB patient records, of which 1,249 (26.0%) had HIV-positive or unknown HIV status documented, and the 574 (45.9%) HIV-positive TB patients were evaluated for timing of ART uptake relative to TB treatment. Among 484 (84.3%) HIV-positive TB patients not already on ART, 256 (52.9%, 95% CI: 45.0–60.8) were not initiated on ART during six months of TB treatment. 30.0% of 273 patients with a known CD4≥50cells/μL started ART within eight weeks, and 14.8% of 54 patients with a known CD4<50cells/μL started within the recommended two weeks. Only 42% of health workers interviewed reported knowing to interpret guidelines on when to initiate ART in HIV-positive TB patients based on CD4 cell count results. CD4 cell count significantly predicted timely ART uptake.ConclusionA large proportion of HIV-positive TB patients were not initiated on ART early or even at all during TB treatment. Retraining of staff, and interventions to strengthen referral systems should be implemented to ensure timely provision of ART among HIV-positive TB patients in Nigeria.

Decline in adverse outcomes and death in tuberculosis patients in Malawi: association with HIV interventions.

Between 2000 and 2012, the annual numbers of patients treated for tuberculosis (TB) in Malawi declined by 28%, from 28 234 to 20 463. During this time, the proportion of TB patients tested for the human immunodeficiency virus (HIV) increased from 6% to 87%. Most HIV-infected patients received cotrimoxazole preventive therapy, and the proportion receiving antiretroviral therapy increased to 88%. Between 2000 and 2008 there was a significant decline in all adverse outcomes (from 31% to 14%), and particularly in deaths (from 23% to 10%) and loss to follow-up (from 5.2% to 1.9%, P < 0.001). After 2008, there was no decrease in any adverse outcome. Ways to further reduce TB-associated mortality are discussed.

Mortality hazard and survival after tuberculosis treatment.

We compared mortality among tuberculosis (TB) survivors and a similar population. We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention's National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk.

Differences between Risk Factors Associated with Tuberculosis Treatment Abandonment and Mortality.

Objectives. To identify the risk factors that were associated with abandonment of treatment and mortality in tuberculosis (TB) patients. Methods. This study was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2002 and 2008 in a TB reference center. Results. A total of 1,257 patients were evaluated, with 69.1% men, 54.4% under 40 years of age, 18.9% with extrapulmonary disease, and 9.3% coinfected with HIV. The risk factors that were associated with abandonment of treatment included male gender (OR = 2.05; 95% CI = 1.15–3.65) and nonadherence to previous treatment (OR = 3.14; 95% CI = 1.96–5.96). In addition, the presence of extrapulmonary TB was a protective factor (OR = 0.33, 95% CI = 0.14–0.76). The following risk factors were associated with mortality: age over 40 years (OR = 2.61, 95% CI = 1.76–3.85), coinfection with HIV (OR = 6.01, 95% CI = 3.78–9.56), illiteracy (OR = 1.88, 95% CI = 1.27–2.75), the presence of severe extrapulmonary TB (OR = 2.33, 95% CI = 1.24–4.38), and retreatment after relapse (OR = 1.95, 95% CI = 1.01–3.75). Conclusions. Male gender and retreatment after abandonment were independent risk factors for nonadherence to TB treatment. Furthermore, age over 40 years, coinfection with HIV, illiteracy, severe extrapulmonary TB, and retreatment after relapse were associated with higher TB mortality. Therefore, we suggest the implementation of direct measures that will control the identified risk factors to reduce the rates of treatment failure and TB-associated mortality.

Longer hospital stay is associated with higher rates of tuberculosis-related morbidity and mortality within 12 months after discharge in a referral hospital in Sub-Saharan Africa.

BackgroundNosocomial transmission of pulmonary tuberculosis (PTB) is a problem in resource-limited settings. However, the degree of TB exposure and the intermediate- and long-term morbidity and mortality of hospital-associated TB is unclear. In this study we determined: 1) the nature, patterns and intensity of TB exposure occurring in the context of current TB cohorting practices in medical centre with a high prevalence of TB and HIV; 2) the one-year TB incidence after discharge; and 3) one-year TB-related mortality after hospital discharge.MethodsFactors leading to nosocomial TB exposure were collected daily over a 3-month period. Patients were followed for 1-year after discharge. TB incidence and mortality were calculated and logistic regression was used to determine the factors associated with TB incidence and mortality during follow up.Results1,094 patients were admitted to the medical wards between May 01 and July 31, 2010. HIV was confirmed in 690/1,094 (63.1%) of them. A total of 215/1,094 (19.7%) patients were diagnosed with PTB and 178/1,094 (16.3%) patients died during the course of their hospitalization; 12/178 (6.7%) patients died from TB-related complications. Eventually, 916 (83.7%) patients were discharged and followed for one year after it. Of these, 51 (5.6%) were diagnosed with PTB during the year of follow up (annual TB rate of 3,712 cases per 100,000 person per year). Overall, 57/916 (6.2%) patients died during the follow up period, of whom 26/57 (45.6%) died from confirmed TB. One-year TB incidence rate and TB-associated mortality were associated with the number of days that the patient remained hospitalized, the number of days spent in the cohorting bay (regardless of whether the patient was eventually diagnosed with TB or not), and the number and proximity to TB index cases. There was no difference in the performance of each of these 3 measurements of nosocomial TB exposure for the prediction of one-year TB incidence.ConclusionSubstantial TB exposure, particularly among HIV-infected patients, occurs in nosocomial settings despite implementation of cohorting measures. Nosocomial TB exposure is strongly associated with one-year TB incidence and TB-related mortality. Further studies are needed to identify strategies to reduce such exposure among susceptible patients.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Reducing tuberculosis-associated early mortality in antiretroviral treatment programmes in sub-Saharan Africa

Between 8% and 26% of patients starting antiretroviral therapy (ART) in programmes in sub-Saharan Africa die during the first year of ART, with the majority of deaths occurring in the first few months [1]. There is a critical need for effective interventions to reduce this [2]. In this patient group

Prevalence, incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda

Tuberculosis (TB) is the leading cause of death among people with HIV in sub-Saharan Africa. Expanding access to antiretroviral therapy (ART) may reduce the burden of TB, but to what extent is unknown. In a study of 1044 adults who initiated home-based ART in Tororo, Uganda between 1 May 2003 and 30 June 2005, participants were screened for active TB at baseline and then monitored at weekly home visits. Participants with TB at baseline or follow-up were compared with those without TB to determine factors associated with mortality in those with TB. At baseline, 75 (7.2%) subjects had TB and a total of 53 (5.5%) were diagnosed with TB over a median of 1.4 years of follow-up (3.90 cases/100 person years). Cumulative mortality was 17.9/100 person-years for those with TB and 3.8/100 person-years for those without TB (P < 0.001). Mortality was associated with low baseline CD4 cell counts [relative hazard (RH), 0.99 per 1 cell/microl increase; P = 0.03] and marginally associated with a body mass index <or= 18 (RH, 2.04; P = 0.10) and increasing age (RH, 1.04 per year; P = 0.11). TB incidence and TB-associated mortality were highest within the first 6 months of ART and declined to 52% and 61% of expected values, respectively, from months 7 to 18 after ART initiation. TB remains an important cause of illness and death in patients receiving ART in Uganda. However, both appear to decline markedly, after 6 months of ART.