Prognostic values of serum IP-10 and IL-17 in Patients with Pulmonary Tuberculosis

Objective:To identify patients at high risk of relapse after anti-tuberculosis (TB) therapy or with poor long-term outcomes.Methods:Fifty-one patients with pulmonary TB: 7 were classified as high association with both cavitations on initial chest radiography and positive sputum smear/cultures after two months of anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25 low association (LA, neither risk). Serum interferon (IFN)-γ-inducible protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were investigated.Results:There was a trend towards higher serum IP-10 levels (p= 0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10 levels were higher in the HA than in the MA/LA group (656.2 ± 234.4 vs. 307.6 ± 258.5 pg/ml, adjustedp= 0.005). Receiver operating characteristic curves showed that the risk of relapse was well-captured by month-2 IP-10 levels at a cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75–0.97,p= 0.003). Month-2 serum IL-17 levels were lower in non-survivors than survivors (15.7 ± 2.9 pg/ml vs. 24.6 ± 8.2 pg/ml,p= 0.001). Multivariate analysis demonstrated that a month-2 serum IL-17 level of ≤ 17 pg/ml (p= 0.026) was independently associated with all-cause mortality.Conclusions:Serum IP-10 and IL-17 levels after 2 months of anti-TB treatment may be biomarkers for estimating risk of both cavitation and delayed sputum conversion, and for predicting long-term mortality, respectively.

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The Prevalence of Absolute and Functional Iron Deficiency Anemia in New Cases of Smear-positive Pulmonary Tuberculosis and Their Sputum Conversion Rate at the End of Intensive Tuberculosis Treatment Phase

Prague Medical Report ◽

10.14712/23362936.2020.3 ◽

2020 ◽

Vol 121 (1) ◽

pp. 35-41

Author(s):

Maliheh Metanat ◽

Mohammad Ali Mashhadi ◽

Roya Alavi-Naini ◽

Leli Rezaie-Kahkhaie ◽

Nahid Sepehri-Rad ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Treatment Phase ◽

Deficiency Anemia ◽

Sputum Smear ◽

Tb Treatment ◽

Significant Difference ◽

Smear Positive Pulmonary Tuberculosis ◽

Sputum Conversion ◽

Positive Sputum Smear

About one third of the population is infected with tuberculosis (TB). On the other hand, iron deficiency is the most common micronutrient deficiency in the world. A number of studies have documented anemia in patients with TB, however, this study aimed to assess the prevalence of iron deficiency anemia (IDA) in patients with acid-fast bacilli (AFB) sputum smear-positive, and sputum conversion in these two groups of patients with absolute and functional IDA at the end of the second month of anti-TB therapy in Zahedan, Iran. The results of this study revealed that 91 out of 198 (45.9%) sputum positive pulmonary TB patients were anemic, and among those 72 (79.1%) had iron deficiency anemia. The overall prevalence of IDA in this study was 36.3%. In 72 patients with IDA, 54 (75%) had functional while the remainder had absolute IDA 18 (25%). Twenty-one out of 72 (29.2%) of patients with IDA remained sputum positive and among 126 non IDA patients 47 (37.3%) had positive sputum smear at the end of intensive TB treatment phase (p=0.278). Approximately, less than half of patients with tuberculosis had anemia among them 79% had iron deficiency anemia. The frequency of functional IDA was three times more than absolute IDA. There was no statistically significant difference in sputum conversion between two groups of IDA and non-IDA patients after intensive phase of anti-TB therapy.

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Risk Factors for Unfavorable Treatment Outcomes among the Human Immunodeficiency Virus-Associated Tuberculosis Population in Tashkent City, Uzbekistan: 2013–2017

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094623 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4623

Author(s):

Sherali Massavirov ◽

Kristina Akopyan ◽

Fazlkhan Abdugapparov ◽

Ana Ciobanu ◽

Arax Hovhanessyan ◽

...

Keyword(s):

Risk Factors ◽

Human Immunodeficiency Virus ◽

Treatment Outcomes ◽

Sputum Smear ◽

People Living With Hiv ◽

Tb Treatment ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Positive Sputum Smear

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection poses a growing clinical challenge. People living with HIV have a higher chance of developing TB, and once the disease has progressed, are at greater risk of having unfavorable TB treatment outcomes. Data on TB treatment outcomes among the HIV-associated TB population in Uzbekistan are limited. Thus, we conducted a cohort study among 808 adult patients with HIV-associated TB registered at the Tashkent TB referral hospital from 2013–2017 to document baseline characteristics and evaluate risk factors for unfavorable TB treatment outcomes. The data were collected from medical records and ambulatory cards. About 79.8% of the study population had favorable treatment outcomes. Antiretroviral therapy (ART) coverage at the admission was 26.9%. Information on CD4-cell counts and viral loads were largely missing. Having extrapulmonary TB (aOR 2.21, 95% CI: 1.38–3.53, p = 0.001), positive sputum smear laboratory results on admission (aOR 1.62, 95% CI: 1.07–2.40), diabetes (aOR 5.16, 95% CI: 1.77–14.98), and hepatitis C (aOR 1.68, 95% CI: 1.14–2.46) were independent risk factors for developing unfavorable TB treatment outcomes. The study findings provide evidence for targeted clinical management in co-infected patients with risk factors. Strengthening the integration of TB/HIV services may improve availability of key data to improve co-infection management.

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Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study

BMC Infectious Diseases ◽

10.1186/s12879-021-06220-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Juliet Namugenyi ◽

Joseph Musaazi ◽

Achilles Katamba ◽

Joan Kalyango ◽

Emmanuel Sendaula ◽

...

Keyword(s):

Bacterial Load ◽

Sputum Smear ◽

People Living With Hiv ◽

Cd4 Cell Count ◽

Cut Point ◽

Ct Value ◽

Tb Treatment ◽

Drug Concentrations ◽

Unit Increase ◽

Sputum Conversion

Abstract Background In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. Methods A subset of 138 PLHIV from the ‘SOUTH’ study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. Results A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient’s colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. Conclusion Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

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Longitudinal body weight and sputum conversion in patients with tuberculosis, Southwest Ethiopia: a retrospective follow-up study

BMJ Open ◽

10.1136/bmjopen-2017-019076 ◽

2018 ◽

Vol 8 (9) ◽

pp. e019076 ◽

Cited By ~ 2

Author(s):

Mersha Filate ◽

Zelalem Mehari ◽

Yihun Mulugeta Alemu

Keyword(s):

Body Weight ◽

Control Strategies ◽

Sputum Smear ◽

Inverse Association ◽

Southwest Ethiopia ◽

Positive Type ◽

Follow Up Study ◽

Tb Treatment ◽

Sputum Conversion

ObjectivesTo describe the association between change in body weight and sputum smear conversion and to identify factors linked with body weight and sputum smear conversion in Jimma University Specialized Hospital, Southwest Ethiopia.DesignA retrospective follow-up study.SettingTeaching hospital in Southwest Ethiopia.ParticipantsA total of 450 patients with tuberculosis (TB) were included in the follow-up between 2011 and 2013.Main outcome measuresThe association between body weight and sputum conversion was measured using joint modelling.ResultsThe association between change in body weight and change in sputum conversion was −0.698 (p<0.001). A strong inverse association between change in body weight and change in sputum conversion was observed. The study variables sex, age, type of TB, HIV status, dose of anti-TB drug and length of enrolment to TB treatment were significantly associated with change in body weight of patients with TB. The study variables age, type of TB, dose of anti-TB drug and length of enrolment were significantly associated with change in sputum status of patients with TB.ConclusionsAmong patients with TB who were on anti-TB treatment, increase in body weight and positive sputum status were inversely related over time. TB prevention and control strategies should give emphasis on factors such as female sex, older age, non-pulmonary positive type of TB, HIV-positive, lower dose of anti-TB drug and length of enrolment to TB treatment during monitoring of trends in body weight and sputum status.

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Decreased Osteopontin Expression as a Reliable Prognostic Indicator of Improvement in Pulmonary Tuberculosis: Impact of the Level of Interferon-γ-Inducible Protein 10

Cellular Physiology and Biochemistry ◽

10.1159/000438559 ◽

2015 ◽

Vol 37 (5) ◽

pp. 1983-1996 ◽

Cited By ~ 11

Author(s):

Yunan Zhu ◽

Hongyu Jia ◽

Jianing Chen ◽

Guangying Cui ◽

Hainv Gao ◽

...

Keyword(s):

Mononuclear Cells ◽

Inflammatory Diseases ◽

Prognostic Indicator ◽

Interferon Γ ◽

Sputum Smear ◽

Peripheral Blood Mononuclear ◽

Pulmonary Tb ◽

Tb Treatment ◽

Before And After ◽

Inducible Protein

Background/Aims: Osteopontin (OPN) expression is increased during the course of various chronic inflammatory diseases, including tuberculosis (TB). However, its prognostic value in TB management remains unclear. This study aimed to determine whether OPN could associate with other cytokines serving as a reliable biomarker for evaluating the effectiveness of early anti-TB treatments. Methods: Smear-positive pulmonary TB patients (n = 20) were recruited, and the plasma levels of OPN, IP-10, TNF-α, and IL-12 were measured by ELISA before initiation of anti-TB therapy and after sputum smear conversion. The C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were also tracked during anti-TB treatment. Results: OPN expression was significantly elevated in patients with smear-positive pulmonary TB, and was closely related with disease severity. Monitoring during the treatment course revealed that its expression, along with that of IFN-γ-induced protein 10 (IP-10), decreased significantly only after sputum smear conversion. Moreover, OPN levels positively correlated with CRP levels before and after anti-TB treatment. Furthermore, OPN markedly promoted IP-10 expression in peripheral blood mononuclear cells. Conclusion: Association between OPN and IP-10 may serve as a reliable prognostic indicator for improvement during the early treatment of pulmonary TB, and may help clinicians in tailoring an effective TB treatment regimen.

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Mobile health to improve adherence to tuberculosis treatment in Khartoum state, Sudan

Journal of Public Health in Africa ◽

10.4081/jphia.2019.1101 ◽

2020 ◽

Vol 10 (2) ◽

Author(s):

Ahmed Osman Ahmed Ali ◽

Martin H. Prins

Keyword(s):

Intervention Group ◽

Control Group ◽

Sputum Smear ◽

Related Factors ◽

Tb Treatment ◽

Treatment Default ◽

Sms Reminder ◽

Positive Sputum Smear ◽

Impact On Treatment ◽

And Control

Although tuberculosis is a treatable disease, the high frequency of treatment default remains a challenge. The use of mobile phones structurally in a TB program has the potential to lower the frequency of default. However, it’s impact on treatment outcome in Sudan has not yet been evaluated. The aim is to evaluate the potential use of cell phones for lowering treatment default. We conducted a controlled intervention pilot study during the period from 1st of May 2017 to 31st of March 2018, in eight TB treatment units in Khartoum state, Sudan. Newly diagnosed patient with positive sputum smear on DOTS therapy were enrolled in intervention and control groups. SMS reminder were sent to the intervention group.Assessments were done at the beginning and at the end of the treatment. One hundred and forty-eight patients were enrolled, seventy-four patients in each group.The participants in the two groups were similar in demographic characteristics and behavioral and knowledge related factors about TB disease at baseline. The patients in the intervention group had a lower default rate (6.8%), higher documented cure rate (78.4%), better knowledge compared to control group. SMS reminder was useful and facilitated good interaction between patients and health personnel. Mobile texting seemed useful and was highly accepted by participants. Further evaluation of it’s potential benefit was warranted.

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The long term effect of pulmonary tuberculosis on income and employment in a low income, urban setting

Thorax ◽

10.1136/thoraxjnl-2020-215338 ◽

2020 ◽

pp. thoraxjnl-2020-215338

Author(s):

Jamilah Meghji ◽

Stefanie Gregorius ◽

Jason Madan ◽

Fatima Chitimbe ◽

Rachael Thomson ◽

...

Keyword(s):

Low Income ◽

Disease Onset ◽

Treatment Completion ◽

Well Being ◽

Urban Setting ◽

Financial Strain ◽

First Episode ◽

Health Seeking ◽

Tb Treatment

BackgroundMitigating the socioeconomic impact of tuberculosis (TB) is key to the WHO End TB Strategy. However, little known about socioeconomic well-being beyond TB-treatment completion. In this mixed-methods study, we describe socioeconomic outcomes after TB-disease in urban Blantyre, Malawi, and explore pathways and barriers to financial recovery.MethodsAdults ≥15 years successfully completing treatment for a first episode of pulmonary TB under the National TB Control Programme were prospectively followed up for 12 months. Socioeconomic, income, occupation, health seeking and cost data were collected. Determinants and impacts of ongoing financial hardship were explored through illness narrative interviews with purposively selected participants.Results405 participants were recruited from February 2016 to April 2017. Median age was 35 years (IQR: 28–41), 67.9% (275/405) were male, and 60.6% (244/405) were HIV-positive. Employment and incomes were lowest at TB-treatment completion, with limited recovery in the following year: fewer people were in paid work (63.0% (232/368) vs 72.4% (293/405), p=0.006), median incomes were lower (US$44.13 (IQR: US$0–US$106.15) vs US$72.20 (IQR: US$26.71–US$173.29), p<0.001), and more patients were living in poverty (earning <US$1.90/day: 57.7% (211/366) vs 41.6% (166/399), p<0.001) 1 year after TB-treatment completion compared with before TB-disease onset. Half of the participants (50.5%, 184/368) reported ongoing dissaving (use of savings, selling assets, borrowing money) and 9.5% (35/368) reported school interruptions in the year after TB-treatment completion. Twenty-one participants completed in-depth interviews. Reported barriers to economic recovery included financial insecurity, challenges rebuilding business relationships, residual physical morbidity and stigma.ConclusionsTB-affected households remain economically vulnerable even after TB-treatment completion, with limited recovery in income and employment, persistent financial strain requiring dissaving, and ongoing school interruptions. Measures of the economic impact of TB disease should include the post-TB period. Interventions to protect the long-term health and livelihoods of TB survivors must be explored.

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Long-term mortality and active TB disease among patients who were lost to follow-up during second line tuberculosis treatment in 2011-2014: population-based study in the country of Georgia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab127 ◽

2021 ◽

Author(s):

Giorgi Kuchukhidze ◽

Davit Baliashvili ◽

Natalia Adamashvili ◽

Ana Kasradze ◽

Russell R Kempker ◽

...

Keyword(s):

Multivariable Analysis ◽

Positive Culture ◽

Population Based ◽

Drug Resistant ◽

Second Line ◽

Adjusted Risk ◽

Tb Treatment ◽

Country Of Georgia

Abstract BACKGROUND High rates of loss to follow-up (LFU) exist among patients with multi-drug and extensively drug-resistant tuberculosis (M/XDR TB); We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment. METHODS We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011-2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture. RESULTS Follow-up information was obtained for 461 patients, among these patients, 107 (23%) died and 177 (38%) were contacted, of those contacted 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time-period for transmitting drug-resistant TB in the community of 480 days (IQR=803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio=13.3, 95% CI: 4.2, 42.2) CONCLUSIONS Nearly one-quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, one in seven remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment.

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Activation of Glutamate Transporter-1 (GLT-1) Confers Sex-Dependent Neuroprotection in Brain Ischemia

Brain Sciences ◽

10.3390/brainsci11010076 ◽

2021 ◽

Vol 11 (1) ◽

pp. 76

Author(s):

Flavia A. Tejeda-Bayron ◽

David E. Rivera-Aponte ◽

Christian J. Malpica-Nieves ◽

Gerónimo Maldonado-Martínez ◽

Héctor M. Maldonado ◽

...

Keyword(s):

Infarct Size ◽

Glutamate Transporter ◽

Triphenyltetrazolium Chloride ◽

Stroke Outcomes ◽

Female Mice ◽

Protein Levels ◽

Translational Activator ◽

Glutamate Transporter 1 ◽

Sensorimotor Performance

Stroke is one of the leading causes of long-term disability. During ischemic stroke, glutamate is released, reuptake processes are impaired, and glutamate promotes excitotoxic neuronal death. Astrocytic glutamate transporter 1 (GLT-1) is the major transporter responsible for removing excess glutamate from the extracellular space. A translational activator of GLT-1, LDN/OSU 0212320 (LDN) has been previously developed with beneficial outcomes in epileptic animal models but has never been tested as a potential therapeutic for ischemic strokes. The present study evaluated the effects of LDN on stroke-associated brain injury. Male and female mice received LDN or vehicle 24 h before or 2 h after focal ischemia was induced in the sensorimotor cortex. Sensorimotor performance was determined using the Rung Ladder Walk and infarct area was assessed using triphenyltetrazolium chloride staining. Males treated with LDN exhibited upregulated GLT-1 protein levels, significantly smaller infarct size, and displayed better sensorimotor performance in comparison to those treated with vehicle only. In contrast, there was no upregulation of GLT-1 protein levels and no difference in infarct size or sensorimotor performance between vehicle- and LDN-treated females. Taken together, our results indicate that the GLT-1 translational activator LDN improved stroke outcomes in young adult male, but not female mice.

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Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver

Cells ◽

10.3390/cells8060610 ◽

2019 ◽

Vol 8 (6) ◽

pp. 610 ◽

Cited By ~ 2

Author(s):

Volker Kinast ◽

Stefan L. Leber ◽

Richard J. P. Brown ◽

Gabrielle Vieyres ◽

Patrick Behrendt ◽

...

Keyword(s):

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Ectopic Expression ◽

Host Factor ◽

Hcv Infection ◽

Mrna Levels ◽

Structural Support ◽

Protein Levels ◽

Inducible Protein

Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus.

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