Impact on Patients’ Treatment Outcomes of XpertMTB/RIF Implementation for the Diagnosis of Tuberculosis: Follow-Up of a Stepped-Wedge Randomized Clinical Trial

Introduction

The impact on treatment outcomes of XpertMTB/RIF, a molecular-based test that provides rapid diagnosis of tuberculosis (TB) and rifampicin resistance with high accuracy, has not been reported despite its adoption in a few countries. We here report treatment outcomes in a step-wedged cluster randomized trial for patients diagnosed with XpertMTB/RIF compared to patients diagnosed with sputum smear examination in public health facilities in Brazil.

Methods

Treatment outcome data were added to the trial database of patients diagnosed from 4 February to 4 October 2012, and crosschecked with data from the national mortality and the drug-resistant TB registers. Treatment outcomes in the intervention (n=2232) and baseline (n=1856) arms were compared using a multilevel regression model.

Results

Unfavourable outcomes were frequent in both arms, mainly due to loss to follow-up (16%). Overall unfavourable outcomes were not reduced in the intervention arm (29.6% versus 31.7%, OR=0.93; 95%CI=0.79-1.08). However, the overall TB-attributed death rate was lower in the intervention arm (2.3% vs. 3.8%). Adjusted for HIV status, age group and city, the intervention resulted in a 35% decrease in TB-attributed deaths (OR=0.65, 95%CI=0.44-0.97).

Conclusions

The proportion of patients successfully treated did not increase with Xpert MTB/RIF implementation, with high loss to follow-up rates in both arms. We did observe a 35% reduction in TB-related mortality, which we hypothesize may be explained by less advanced disease among the smear-negative patients diagnosed by Xpert. In conclusion, XpertMTB/RIF introduction did not improve TB treatment outcomes in Brazil.

Trial Registration

clinicaltrials.gov NCT01363765     

Missed Opportunities for TB Investigation in Primary Care Clinics in South Africa: Experience from the XTEND Trial

Setting

40 primary health clinics (PHCs) in four provinces in South Africa, June 2012 –February 2013.

Objective

To determine whether health care worker (HCW) practice in investigating people with TB symptoms was altered when the initial test for TB was changed from smear microscopy to Xpert MTB/RIF.

Design

Cross-sectional substudy at clinics participating in a pragmatic cluster randomised trial, Xpert for TB: Evaluating a New Diagnostic "XTEND", which evaluated the effect of Xpert MTB/RIF implementation in South Africa.

Methods

Consecutive adults exiting PHCs reporting at least one TB symptom (defined as any of cough, weight loss, night sweats and fever) were enrolled. The main outcome was the proportion who self-reported having sputum requested by HCW during the clinic encounter just completed.

Results

3604 adults exiting PHCs (1676 in Xpert arm, 1928 in microscopy arm) were enrolled (median age 38 years, 71.4% female, 38.8% reported being HIV-positive, 70% reported cough). For 1267 participants (35.2%) the main reason for attending the clinic was TB symptom(s).Overall 2130/3604 (59.1%) said they reported their symptom(s) to HCW. 22.7% (818/3604) reported having been asked to give sputum for TB investigation. Though participants in the Xpert vs. microscopy arm were more likely to have sputum requested by HCW, this was not significantly different: overall (26.0% [436/1676] vs 19.8% [382/1928]; adjusted prevalence ratio [aPR] 1.31, [95% CI 0.78–2.20]) and when restricted to those presenting at clinics due to symptoms (49.1% [260/530] vs 29.9% [220/737]; aPR 1.38 [0.89–2.13]) and those reporting being HIV-positive (29.4% [190/647] vs 20.8% [156/749]; aPR 1.38[0.88–2.16]).Those attending clinic due to TB symptoms, were more likely to have sputum requested if they had increasing number of symptoms; longer duration of cough, unintentional weight loss and night sweats and if they reported symptoms to HCW.

Conclusions

A large proportion of people exiting PHCs reporting TB symptoms did not get tested. Implementation of Xpert MTB/RIF did not substantially change the probability of testing for TB. Better systems are needed to ensure that opportunities to identify active TB among PHC attendees are not missed.     

The Diagnostic Accuracy of Urine Lipoarabinomannan Test for Tuberculosis Screening in a South African Correctional Facility

Background

We evaluated the diagnostic accuracy of the urine lipoarabinomannan (LAM) antigen detection assay (Clearview TB-ELISA) to screen for tuberculosis in a South African correctional facility.

Methods

Between September 2009 and October 2010, male offenders were screened for tuberculosis (symptoms, chest radiograph, two spot sputum specimens for microscopy and culture), and urine tested for LAM. Sensitivity, specificity and predictive values of LAM were calculated using definite and probable tuberculosis combined as our gold standard.

Findings

33/871 (3.8%) participants (26% HIV-positive) had tuberculosis. Amongst HIV-positive vs. HIV-negative offenders the sensitivity and specificity of LAM was 7.1% vs. 0% and 98.5% vs. 99.8% respectively.

Conclusion

Urine LAM ELISA has inadequate sensitivity for TB screening in this population.     

High Prevalence of HIV Infection and Bisexual Networks among a Sample of Men Who Have Sex with Men in Eastern China

Objective

To examine homosexual and heterosexual behaviors, behavioral networks and HIV infection among men who have sex with men (MSM) in Eastern China.

Methods

A cross-sectional survey was conducted among MSM in 2013 in a rural prefecture of Zhejiang province. Participants were interviewed for their sexual behaviors and sexual networks and were tested for HIV infection.

Results

A total of 620 MSM from gay bath houses and bars participated in the survey. Of them, 58.2% aged 18 to 39 years and 49.5% were currently married with a female. The age of first homosexual contact was 26.7 years on average, ranging from 12 to 66 years. 91.0% had multiple male sex partners and 86.1% also had female sex partners in lifetime. 70 (11.3%) of the participants were tested HIV-positive. A total of 620 independent egocentric sexual networks involving 620 study participants and 1,971 reported sexual partners in the past 12 months were constructed, including 70 networks for the 70 HIV-positive participants with their 221 sexual partners and 550 networks for the 550 HIV-negative participants with their 1,750 sexual partners. The median network degree was 3 (IQR 2-4) overall and was not different between HIV-positive participants (Median: 3; IQR: 2-4) and HIV-negative participants (Median: 3; IQR: 2-4) (Mann-Whitney test, Z=-0.015, P=0.998). The proportion of networks with a multiple male sexual partnership was 63.7% overall, 62.8% for HIV-positive participants and 63.8% for HIV-negative participants (χ²=0.025, P=0.875). The proportion of networks with both male and female sexual partners was 44.8% overall, 47.1% for HIV-positive participants and 44.5% for HIV-negative participants (χ²=0.169, P=0.681). Consistent condom use and knowledge of HIV infection status were rare within the network partners.

Conclusions

The currently high HIV prevalence and complicated bisexual networks among MSM in the study area provides enhanced evidence for developing tailored prevention strategies for HIV transmission among and beyond the MSM population.     

Comparison of Treatment Outcomes of New Smear-Positive Pulmonary Tuberculosis Patients by HIV and Antiretroviral Status in a TB/HIV Clinic,Malawi

Background

Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues.

Methods

All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi’s largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression.

Results

Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14–1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29–2.60).

Conclusion

HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.     

A Diagnostic Accuracy Study of Xpert?MTB/RIF in HIV-Positive Patients with High Clinical Suspicion of Pulmonary Tuberculosis in Lima,Peru

Background

Diagnosis of pulmonary tuberculosis (TB) among human immunodeficiency virus (HIV) patients remains complex and demands easy to perform and accurate tests. Xpert®MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid and convenient; the test requires minimal human resources and reports results within two hours. The majority of performance studies of MTB/RIF have been performed in high HIV burden settings, thus TB diagnostic studies among HIV patients in low HIV prevalence settings such as Peru are still needed.

Methodology/Principal Findings

From April 2010 to May 2011, HIV-positive patients with high clinical suspicion of TB were enrolled from two tertiary hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite reference standard Löwenstein-Jensen (LJ) and liquid culture. Detection of rifampicin resistance was compared to the LJ proportion method. We included 131 patients, the median CD4 cell count was 154.5 cells/mm³ and 45 (34.4%) had TB. For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI 88.4–99.6) (44/45); specificity was 97.7% (95% CI 91.9–99.4) (84/86); the positive predictive value was 95.7% (95% CI 85.5–98.8) (44/46); and the negative predictive value, 98.8% (95% CI 93.6–99.8) (84/85). MTB/RIF detected 13/14 smear-negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9% (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF was 100% (95% CI 61.0–100.0) (6/6); specificity was 91.0% (95% CI 76.4–96.9) (30/33); the positive predictive value was 66.7% (95% CI 35.4–87.9) (6/9); and the negative predictive value was 100% (95% CI 88.7 –100.0) (30/30).

Conclusions/Significance

In HIV patients in our population with a high clinical suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear microscopy.     

High Proportion of HIV Serodiscordance among HIV-Affected Married Couples in Northern Vietnam

Introduction

Little is known about the state of HIV transmission among married couples in Vietnam. This study aims to clarify HIV serostatus in this group and elucidate risk factors for intra-marital HIV transmission.

Methods

In 2012, we enrolled a group of HIV-positive married men registered at the HIV outpatient clinic of a referral hospital in northern Vietnam, along with their wives. Sociodemographic, behavioural and clinical data were collected from men and wives. HIV serodiscordant couples were followed until March 2014 to determine seroconversion rate. A phylogenetic analysis was performed based on env V3 sequence to detail cluster formation among men.

Results

Of the 163 HIV-positive men enrolled in the study, 101 (62.0%) had wives testing HIV-negative. Half of men reported injecting drug use (IDU) as a likely transmission route. Couples reported a high incidence of unprotected sexual intercourse prior to diagnosis; the median (inter quartile range) was 4 (4–8) times per month. Only 17 couples (10.4%) reported using condoms during at least half these instances. Multivariable analysis revealed IDU history among men was independently associated with HIV-negative wives (adjusted OR 0.31; 95% CI 0.10–0.95, p=0.041). Phylogenetic analysis of 80 samples indicated CRF01_AE. Of these, 69 (86.3%) clustered with IDU-associated viruses from Vietnam. No HIV seroconversion was identified during a follow-up of 61 serodiscordant couples, with 126.5 person-years of observation during which HIV-infected men were on antiretroviral drug therapy (ART).

Conclusion

High HIV serodiscordance was observed among HIV-affected married couples in northern Vietnam. A large number of at-risk wives therefore remain HIV-negative and can be protected with measures including proper use of ART if couples are made aware of the serodiscordance through screening.     

Risk Factors for Vitamin D Deficiency among Veterans with and without HIV Infection

Objectives

We aimed to describe and compare the prevalence of vitamin D deficiency between HIV-negative and HIV-infected veterans in the southern United States, and to determine risk factors for vitamin D deficiency for HIV infected patients.

Methods

Cross-sectional, retrospective study including all patients followed at the Atlanta VA Medical Center with the first 25-hydroxyvitamin D [25(OH)D] level determined between January 2007 and August 2010. Multivariate logistic regression analysis was used to determine risk factors associated with vitamin D deficiency (< 20 ng/ml).

Results

There was higher prevalence of 25(OH)D deficiency among HIV-positive compared to HIV-negative patients (53.2 vs. 38.5%, p <0.001). Independent risk factors for vitamin D deficiency in HIV + patients included black race (OR 3.24, 95% CI 2.28–4.60), winter season (OR 1.39, 95% CI 1.05–1.84) and higher GFR (OR 1.01, CI 1.00–1.01); increasing age (OR 0.98, 95% CI 0.95–0.98), and tenofovir use (OR 0.72, 95% CI 0.54–0.96) were associated with less vitamin D deficiency.

Conclusions

Vitamin D deficiency is a prevalent problem that varies inversely with age and affects HIV-infected patients more than other veterans in care. In addition to age, tenofovir and kidney disease seem to confer a protective effect from vitamin D deficiency in HIV-positive patients.     

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

Purpose

To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls.

Methods

Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness.

Results

Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm²). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls.

Conclusion

Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.     

Burden of new and recurrent tuberculosis in a major South African city stratified by age and HIV-status

Aim

To describe the burden of tuberculosis (TB) in Cape Town by calculating TB incidence rates stratified by age and HIV-status, assessing the contribution of retreatment disease and estimating the cumulative lifetime TB risk in HIV-negative individuals.

Methods

Details of TB cases were abstracted from the 2009 electronic TB register. Population denominators were estimated from census data and actuarial estimates of HIV prevalence, allowing calculation of age-specific and HIV-stratified TB notification rates.

Results

The 2009 mid-year population was 3,443,010 (3,241,508 HIV-negative and 201,502 HIV-positive individuals). There were 29,478 newly notified TB cases of which 56% were laboratory confirmed. HIV status was recorded for 87% of cases and of those with known HIV-status 49% were HIV-negative and 51% were positive. Discrete peaks in the incidence of non-HIV-associated TB occurred at three ages: 511/100,000 at 0–4 years of age, 553/100,000 at 20–24 years and 628/100,000 at 45–49 years with 1.5%, 19% and 45% being due to retreatment TB, respectively. Only 15.5% of recurrent cases had a history of TB treatment failure or default. The cumulative lifetime risks in the HIV-negative population of all new TB episodes and new smear-positive TB episodes were 24% and 12%, respectively; the lifetime risk of retreatment disease was 9%. The HIV-positive notification rate was 6,567/100,000 (HIV-associated TB rate ratio = 17). Although retreatment cases comprised 30% of the HIV-associated TB burden, 88% of these patients had no history of prior treatment failure or default.

Conclusions

The annual burden of TB in this city is huge. TB in the HIV-negative population contributed almost half of the overall disease burden and cumulative lifetime risks were similar to those reported in the pre-chemotherapy era. Retreatment TB contributed significantly to both HIV-associated and non-HIV-associated TB but infrequently followed prior inadequate treatment. This likely reflects ongoing TB transmission to both HIV-negative and positive individuals.     

Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials

Background

Infection with Human Immunodeficiency virus (HIV) is an important risk factor for Tuberculosis (TB). Anti-Retroviral Therapy (ART) has improved the prognosis of HIV and reduced the risk of TB infected patients. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB.

Objective

Systematically review and synthesize effect estimates of IPT for TB prevention in adult HIV patients. Secondary objectives were to assess the effect of IPT on HIV disease progression, all-cause mortality and adverse drug reaction (ADR).

Search Strategy

Electronic databases were searched to identify relevant articles in English available by September 11^th 2015.

Selection Criteria

Research articles comparing IPT to placebo or no treatment in HIV infected adults using randomized clinical trials.

Data Analysis

A qualitative review included study-level information on randomization and treatment allocation. Effect estimates were pooled using random-effects models to account for between-study heterogeneity.

Main Results

This review assessed ten randomized clinical trials that assigned 7619 HIV patients to IPT or placebo. An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, however, larger benefit of IPT was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81. There was no statistically significant effect of IPT on TB occurrence in TST negative or unknown participants. IPT also reduced the risk of HIV disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata. All-cause mortality was not affected by IPT although participants who had 12 months of IPT tend to have a reduced risk (RR = 0.65; 95% CI(0.47, 0.90)). IPT had an elevated, yet statistically non-significant, risk of adverse drug reaction [RR = 1.20; 95% CI (1.20, 1.71)]. Only a single study assessed the effect of IPT in combination with ART in preventing TB and occurrence of multi-drug resistant tuberculosis.

Conclusions

IPT use substantially contributes in preventing TB in persons with HIV in general and in TST positive individuals in particular. More evidence is needed to explain discrepancies in the protective effect of IPT in these individuals.     

The Burden of Drug-Resistant Tuberculosis in Papua New Guinea: Results of a Large Population-Based Survey

Background

Reliable estimates of the burden of multidrug-resistant tuberculosis (MDR-TB) are crucial for effective control and prevention of tuberculosis (TB). Papua New Guinea (PNG) is a high TB burden country with limited information on the magnitude of the MDR-TB problem.

Methods

A cross-sectional study was conducted in four PNG provinces: Madang, Morobe, National Capital District and Western Province. Patient sputum samples were tested for rifampicin resistance by the Xpert MTB/RIF assay and those showing the presence of resistance underwent phenotypic susceptibility testing to first- and second-line anti-TB drugs including streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, ofloxacin, amikacin, kanamycin and capreomycin.

Results

Among 1,182 TB patients enrolled in the study, MDR-TB was detected in 20 new (2.7%; 95% confidence intervals [CI] 1.1–4.3%) and 24 previously treated (19.1%; 95%CI: 8.5–29.8%) TB cases. No case of extensively drug-resistant TB (XDR-TB) was detected. Thirty percent (6/20) of new and 33.3% (8/24) of previously treated cases with MDR-TB were detected in a single cluster in Western Province.

Conclusion

In PNG the proportion of MDR-TB in new cases is slightly lower than the regional average of 4.4% (95%CI: 2.6–6.3%). A large proportion of MDR-TB cases were identified from a single hospital in Western Province, suggesting that the prevalence of MDR-TB across the country is heterogeneous. Future surveys should further explore this finding. The survey also helped strengthening the use of smear microscopy and Xpert MTB/RIF testing as diagnostic tools for TB in the country.     

Characteristics of Patients with Smear-Negative Pulmonary Tuberculosis (TB) in a Region with High TB and HIV Prevalence

Introduction

Smear-negative pulmonary TB (SNPT) represents 30–60% of all pulmonary TB cases. The mortality of these patients can reach 25% in populations with high prevalence of HIV infection, and 10–20% of TB transmission at the population level are attributable to SNPT cases.

Methods

We conducted a retrospective study to evaluate epidemiological, clinical, and radiological characteristics of patients with SNPT and to compare these with patients who were diagnosed as having smear-positive pulmonary TB (SPPT). All adult patients (≥ 18 years old) with a positive culture for Mycobacterium tuberculosis, and a diagnosis of pulmonary TB were included in the study.

Results

198 patients met the inclusion criteria (positive culture for Mycobacterium tuberculosis) and were included in the analysis. Of these patients, 69 (34.8%) were smear positive (SPPT) and 129 (65.2%) were smear negative (SNPT). In univariate analysis, cough, dyspnea, and hemoptysis were less frequent in SNPT patients in comparison with SPPT patients. In a multivariate model, having no cough and no radiographic pattern typical of TB were the characteristics independently associated with a diagnosis of SNPT.

Conclusions

We found a very high prevalence of SNPT among patients with TB in a setting with high TB and HIV prevalence. The absence of cough in the presence of other symptoms suggestive of TB, and having no radiographic pattern typical of TB where independent predictors of SNPT.     

TB Treatment Delays in Odisha,India: Is It Expected Even after These Many Years of RNTCP Implementation?

Background

In India, the Revised National TB Control Programme (RNTCP) envisages initiation of TB treatment within seven days of diagnosis among smear-positive patients. After nearly two decades of RNTCP implementation, treatment delays are usually not expected.

Objectives

To determine the proportion of sputum smear-positive TB patients who were initiated on treatment after seven days and their associated risk factors.

Methods

The study was conducted in Cuttack and Rayagada districts of Odisha. It was a retrospective cohort study that involves review of TB treatment registers and laboratory registers for 2013.

Results

Among 1,800 pulmonary TB (PTB) patients, 1,074 (60%) had been initiated on treatment within seven days of diagnosis, 721 (40%) had been initiated on treatment more than seven days, and 354 (20%) had delays of more than 15 days. The mean duration between TB diagnosis and treatment initiation was 21 days with a range of 8–207 days (median = 14 days). Odds of treatment delay of more than seven days were 4.9 times (95% confidence interval [CI] 3.3-6.6) among those who had been previously treated, 6.2 times (95% CI 1.3-29.7) among those infected with HIV, and 1.8 times (95% CI 1.1-2.9) among those diagnosed outside district DMC.

Conclusion

Delay in initiation of TB treatment occurred in majority of the smear-positive patients. The RNTCP should focus on core areas of providing quality TB services with time-tested strategies. To have real-time monitoring mechanisms for diagnosed smear-positive TB patients is expected to be the way forward.     

Time to Death and Associated Factors among Tuberculosis Patients in Dangila Woreda,Northwest Ethiopia

Background

Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide. More than 70% of the deaths of TB patients occur during the first two months of TB treatment. The major risk factors that increase early death of TB patients are being positive for human immunodeficiency virus (HIV), being of old age, being underweight or undergoing re-treatment.

Objective

To assess the time of reported deaths and associated factors in a cohort of patients with TB during TB treatment.

Methods

An institution-based retrospective cohort study was analyzed in Dangila Woreda, Northwest Ethiopia from March 1^st through March 30, 2014. All TB patients registered in the direct observed treatment (DOTs) clinic from 2008–2012 were included in the study. Data were entered into EpiData and exported to SPSS for analysis. The survival probability was analyzed by the Kaplan Meier method and Cox regression analysis was applied to investigate factors associated with death during TB treatment.

Results

From a total of 872 cases registered in TB registry log book, 810 were used for the analysis of which 60 (7.4%) died during the treatment. The overall mortality rate was 12.8/1000 person months of observation. A majority of TB deaths 34 (56.7%) occurred during the intensive phase of the treatment, and the median time of death was at two months of the treatment. Age, HIV status and baseline body weight were independent predictors of death during TB treatment.

Conclusions

Most deaths occurred in the first two months of TB treatment. Old age, TB/HIV co-infection and a baseline body weight of <35 kg increased the mortality during TB treatment. Therefore, a special follow up of TB patients during the intensive phase, of older patients and of TB/HIV co-infected cases, as well as nutritionally supplementing for underweight patients may be important to consider as interventions to reduce deaths during TB treatment.     

The High Cost of HIV-Positive Inpatient Care at an Urban Hospital in Johannesburg,South Africa

Background

While most HIV care is provided on an outpatient basis, hospitals continue to treat serious HIV-related admissions, which is relatively resource-intensive and expensive. This study reports the primary reasons for HIV-related admission at a regional, urban hospital in Johannesburg, South Africa and estimates the associated lengths of stay and costs.

Methods and Findings

A retrospective cohort study of adult, medical admissions was conducted. Each admission was assigned a reason for admission and an outcome. The length of stay was calculated for all patients (N = 1,041) and for HIV-positive patients (n = 469), actual utilization and associated costs were also estimated. Just under half were known to be HIV-positive admissions. Deaths and transfers were proportionately higher amongst HIV-positive admissions compared to HIV-negative and unknown. The three most common reasons for admission were tuberculosis and other mycobacterial infections (18%, n = 187), cardiovascular disorders (12%, n = 127) and bacterial infections (12%, n = 121). The study sample utilized a total of 7,733 bed days of those, 55% (4,259/7,733) were for HIV-positive patients. The average cost per admission amongst confirmed HIV-positive patients, which was an average of 9.3 days in length, was $1,783 (United States Dollars).

Conclusions

Even in the era of large-scale antiretroviral treatment, inpatient facilities in South Africa shoulder a significant HIV burden. The majority of this burden is related to patients not on ART (298/469, 64%), and accounts for more than half of all inpatient resources. Reducing the costs of inpatient care is thus another important benefit of expanding access to ART, promoting earlier ART initiation, and achieving rates of ART retention and adherence.     

Factors Associated with Unfavorable Treatment Outcomes in New and Previously Treated TB Patients in Uzbekistan: A Five Year Countrywide Study

Background

TB is one of the main health priorities in Uzbekistan and relatively high rates of unfavorable treatment outcomes have recently been reported. This requires closer analysis to explain the reasons and recommend interventions to improve the situation. Thus, by using countrywide data this study sought to determine trends in unfavorable outcomes (lost-to-follow-ups, deaths and treatment failures) and describe their associations with socio-demographic and clinical factors.

Method

A countrywide retrospective cohort study of all new and previously treated TB patients registered in the National Tuberculosis programme between January 2006 and December 2010.

Results

Among 107,380 registered patients, 67% were adults, with smaller proportions of children (10%), adolescents (4%) and elderly patients (19%). Sixty per cent were male, 66% lived in rural areas, 1% were HIV-infected and 1% had a history of imprisonment. Pulmonary TB (PTB) was present in 77%, of which 43% were smear-positive and 53% were smear-negative. Overall, 83% of patients were successfully treated, 6% died, 6% were lost-to-follow-up, 3% failed treatment and 2% transferred out. Factors associated with death included being above 55 years of age, HIV-positive, sputum smear positive, previously treated, jobless and living in certain provinces. Factors associated with lost-to-follow-up were being male, previously treated, jobless, living in an urban area, and living in certain provinces. Having smear-positive PTB, being an adolescent, being urban population, being HIV-negative, previously treated, jobless and residing in particular provinces were associated with treatment failure.

Conclusion

Overall, 83% treatment success rate was achieved. However, our study findings highlight the need to improve TB services for certain vulnerable groups and in specific areas of the country. They also emphasize the need to develop unified monitoring and evaluation tools for drug-susceptible and drug-resistant TB, and call for better TB surveillance and coordination between provinces and neighbouring countries.     

Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda

Rationale

The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.

Objective

To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.

Methods

We prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.

Results

477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73–84%) and specificity (190/199, 96%, 95% CI: 92–98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31–54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0–26] vs. 0 [IQR 0–1], p<0.001), and for smear-negative TB (35 [IQR 22–55] vs. 22 [IQR 0–33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0–5] vs. 0 [IQR 0–2], p = 0.06) and for smear-negative TB (7 [IQR 3–53] vs. 6 [IQR 1–61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: −21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: −34 to +46%, p = 0.77).

Conclusions

Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.     

Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity

Background

The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

Methodology

Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

Results

A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13–103) versus 2 SFU (1–50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2–16.7) cells/μl versus 2.4 (1.1–4.0) cells/μl; p = 0.041) and IL-10 secreting cells (65 SFU (7–196) versus 1 SFU (0–31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

Conclusions

Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.