TUBERCULOSIS CONFERENCE

Previously Published Papers on "Tuberculosis Conference"

• Evaluating Health-Related Quality of Life of Lost to Follow-Up Tuberculosis Patients in Yemen

  Authors: Ammar Ali Saleh Jaber, Amer Hayat Khan, Syed Azhar Syed Sulaiman, Keywords: Yemen, tuberculosis, health-related quality of life, khat. DOI:10.5281/zenodo.2580962 Abstract: Tuberculosis (TB) is considered as a major disease that affects daily activities and impairs health-related quality of life (HRQoL). The impact of TB on HRQoL can affect treatment outcome and may lead to treatment defaulting. Therefore, this study aims to evaluate the HRQoL of TB treatment lost to follow-up during and after treatment in Yemen. For this aim, this prospective study enrolled a total of 399 TB lost to follow-up patients between January 2011 and December 2015. By applying HRQoL criteria, only 136 fill the survey during treatment. Moreover, 96 were traced and fill out the HRQoL survey. All eight HRQol domains were categorized into the physical component score (PCS) and mental component score (MCS), which were calculated using QM scoring software. Results show that all lost to follow-up TB patients reported a score less than 47 for all eight domains, except general health (67.3) during their treatment period. Low scores of 27.9 and 29.8 were reported for emotional role limitation (RE) and mental health (MH), respectively. Moreover, the mental component score (MCS) was found to be only 28.9. The trace lost follow-up shows a significant improvement in all eight domains and a mental component score of 43.1. The low scores of 27.9 and 29.8 for role emotion and mental health, respectively, in addition to the MCS score of 28.9, show that severe emotional condition and reflect the higher depression during treatment period that can result to lost to follow-up. The low MH, RE, and MCS can be used as a clue for predicting future TB treatment lost to follow-up.

• Identification of Promiscuous Epitopes for Cellular Immune Responses in the Major Antigenic Protein Rv3873 Encoded by Region of Difference 1 of Mycobacterium tuberculosis

  Authors: Abu Salim Mustafa, Keywords: Mycobacterium tuberculosis, Rv3873, peptides, vaccine DOI:10.5281/zenodo.1316664 Abstract: Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

• Antibody Reactivity of Synthetic Peptides Belonging to Proteins Encoded by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions of Differences

  Authors: Abu Salim Mustafa, Keywords: Genomic regions of differences, Mycobacterium tuberculosis, peptides, serodiagnosis. DOI:10.5281/zenodo.1316329 Abstract: The comparisons of mycobacterial genomes have identified several Mycobacterium tuberculosis-specific genomic regions that are absent in other mycobacteria and are known as regions of differences. Due to M. tuberculosis-specificity, the peptides encoded by these regions could be useful in the specific diagnosis of tuberculosis. To explore this possibility, overlapping synthetic peptides corresponding to 39 proteins predicted to be encoded by genes present in regions of differences were tested for antibody-reactivity with sera from tuberculosis patients and healthy subjects. The results identified four immunodominant peptides corresponding to four different proteins, with three of the peptides showing significantly stronger antibody reactivity and rate of positivity with sera from tuberculosis patients than healthy subjects. The fourth peptide was recognized equally well by the sera of tuberculosis patients as well as healthy subjects. Predication of antibody epitopes by bioinformatics analyses using ABCpred server predicted multiple linear epitopes in each peptide. Furthermore, peptide sequence analysis for sequence identity using BLAST suggested M. tuberculosis-specificity for the three peptides that had preferential reactivity with sera from tuberculosis patients, but the peptide with equal reactivity with sera of TB patients and healthy subjects showed significant identity with sequences present in nob-tuberculous mycobacteria. The three identified M. tuberculosis-specific immunodominant peptides may be useful in the serological diagnosis of tuberculosis.

• The Role of Chemokine Family, CXCL-10 Urine as a Marker Diagnosis of Active Lung Tuberculosis in HIV/AIDS Patients

  Authors: Dwitya Elvira, Raveinal Masri, Rohayat Bilmahdi, Keywords: Chemokine, IP-10 urine, HIV/AIDS, Tuberculosis. DOI:10.5281/zenodo.1128889 Abstract: Human Immunodeficiency Virus (HIV) pandemic increased significantly worldwide. The rise in cases of HIV/AIDS was also followed by an increase in the incidence of opportunistic infection, with tuberculosis being the most opportunistic infection found in HIV/AIDS and the main cause of mortality in HIV/AIDS patients. Diagnosis of tuberculosis in HIV/AIDS patients is often difficult because of the uncommon symptom in HIV/AIDS patients compared to those without the disease. Thus, diagnostic tools are required that are more effective and efficient to diagnose tuberculosis in HIV/AIDS. CXCL-10/IP-10 is a chemokine that binds to the CXCR3 receptor found in HIV/AIDS patients with a weakened immune system. Tuberculosis infection in HIV/AIDS activates chemokine IP-10 in urine, which is used as a marker for diagnosis of infection. The aim of this study was to prove whether IP-10 urine can be a biomarker diagnosis of active lung tuberculosis in HIV-AIDS patients. Design of this study is a cross sectional study involving HIV/AIDS patients with lung tuberculosis as the subject of this study. Forty-seven HIV/AIDS patients with tuberculosis based on clinical and biochemical laboratory were asked to collect urine samples and IP-10/CXCL-10 urine being measured using ELISA method with 18 healthy human urine samples as control. Forty-seven patients diagnosed as HIV/AIDS were included as a subject of this study. HIV/AIDS were more common in male than in women with the percentage in male 85.1% vs. 14.5% of women. In this study, most diagnosed patients were aged 31-40 years old, followed by those 21-30 years, and > 40 years old, with one case diagnosed at age less than 20 years of age. From the result of the urine IP-10 using ELISA method, there was significant increase of the mean value of IP-10 urine in patients with TB-HIV/AIDS co-infection compared to the healthy control with mean 61.05 pg/mL ± 78.01 pg/mL vs. mean 17.2 pg/mL. Based on this research, there was significant increase of urine IP-10/CXCL-10 in active lung tuberculosis with HIV/AIDS compared to the healthy control. From this finding, it is necessary to conduct further research into whether urine IP-10/CXCL-10 plays a significant role in TB-HIV/AIDS co-infection, which can also be used as a biomarker in the early diagnosis of TB-HIV.

• Statistical Analysis of Interferon-γ for the Effectiveness of an Anti-Tuberculous Treatment

  Authors: Shishen Xie, Yingda L. Xie, Keywords: Data analysis, interferon gamma release assay, statistical methods, tuberculosis infection. DOI:10.5281/zenodo.1125833 Abstract: Tuberculosis (TB) is a potentially serious infectious disease that remains a health concern. The Interferon Gamma Release Assay (IGRA) is a blood test to find out if an individual is tuberculous positive or negative. This study applies statistical analysis to the clinical data of interferon-gamma levels of seventy-three subjects who diagnosed pulmonary TB in an anti-tuberculous treatment. Data analysis is performed to determine if there is a significant decline in interferon-gamma levels for the subjects during a period of six months, and to infer if the anti-tuberculous treatment is effective.

• Impact of Tuberculosis Co-infection on Cytokine Expression in HIV-Infected Individuals

  Authors: M. Nosik, I. Rymanova, N. Adamovich, S. Sevostyanihin, K. Ryzhov, Y. Kuimova, A. Kravtchenko, N. Sergeeva, A. Sobkin, Keywords: HIV, Tuberculosis, TB, HIV associated with TB, Th1/ Th2 cytokine expression. DOI:10.5281/zenodo.1123554 Abstract: HIV and Tuberculosis (TB) infections each speed the other's progress. HIV-infection increases the risk of TB disease. At the same time, TB infection is associated with clinical progression of HIV-infection. HIV+TB co-infected patients are also at higher risk of acquiring new opportunistic infections. An important feature of disease progression and clinical outcome is the innate and acquired immune responses. HIV and TB, however, have a spectrum of dysfunctions of the immune response. As cytokines play a crucial role in the immunopathology of both infections, it is important to study immune interactions in patients with dual infection HIV+TB. Plasma levels of proinflammatory cytokines IL-2, IFN-γ and immunoregulating cytokines IL-4, IL-10 were evaluated in 75 patients with dual infection HIV+TB, 58 patients with HIV monoinfection and 50 patients with TB monoinfection who were previously naïve for HAART. The decreased levels of IL-2, IFN-γ, IL-4 and IL-10 were observed in patients with dual infection HIV+TB in comparison with patients who had only HIV or TB which means the profound suppression of Th1 and Th2 cytokine secretion. Thus, those cytokines could possibly serve as immunological markers of progression of HIV-infection in patients with TB.

• Surface Thermodynamics Approach to Mycobacterium tuberculosis (M-TB) – Human Sputum Interactions

  Authors: J. L. Chukwuneke, C. H. Achebe, S. N. Omenyi, Keywords: Absorbance, dielectric constant, Hamaker coefficient, Lifshitz formula, macrophage, Mycobacterium tuberculosis, Van der Waals forces. DOI:10.5281/zenodo.1110325 Abstract: This research work presents the surface thermodynamics approach to M-TB/HIV-Human sputum interactions. This involved the use of the Hamaker coefficient concept as a surface energetics tool in determining the interaction processes, with the surface interfacial energies explained using van der Waals concept of particle interactions. The Lifshitz derivation for van der Waals forces was applied as an alternative to the contact angle approach which has been widely used in other biological systems. The methodology involved taking sputum samples from twenty infected persons and from twenty uninfected persons for absorbance measurement using a digital Ultraviolet visible Spectrophotometer. The variables required for the computations with the Lifshitz formula were derived from the absorbance data. The Matlab software tools were used in the mathematical analysis of the data produced from the experiments (absorbance values). The Hamaker constants and the combined Hamaker coefficients were obtained using the values of the dielectric constant together with the Lifshitz Equation. The absolute combined Hamaker coefficients A132abs and A131abs on both infected and uninfected sputum samples gave the values of A132abs = 0.21631x10-21Joule for M-TB infected sputum and Ã132abs = 0.18825x10-21Joule for M-TB/HIV infected sputum. The significance of this result is the positive value of the absolute combined Hamaker coefficient which suggests the existence of net positive van der waals forces demonstrating an attraction between the bacteria and the macrophage. This however, implies that infection can occur. It was also shown that in the presence of HIV, the interaction energy is reduced by 13% conforming adverse effects observed in HIV patients suffering from tuberculosis.

• Awareness about HIV-Infection among HIV-Infected Individuals Attending Medical Moscow Center, Russia

  Authors: Marina Nosik, Irina Rymanova, Sergei Sevostyanihin, Natalya Sergeeva, Alexander Sobkin, Keywords: AIDS, HIV transmission risks, HIV misconceptions, risk behavior. DOI:10.5281/zenodo.1108216 Abstract: This paper presents results of the survey regarding the awareness about HIV/AIDS among HIV-infected individuals. A questionnaire covering various aspects of HIV-infection was conducted among 110 HIV-infected individuals who attended the G.A. Zaharyan Moscow Tuberculosis Clinic, Department for treatment of TB patients with HIV. The questionnaire included questions about modes of HIV transmission and preventive measures against HIV/AIDS, as well as questions about age, gender, education and employment status. The survey revealed that the respondents in the whole had a good knowledge regarding modes of HIV transmission and preventive measures against HIV/AIDS: about 83,6% male respondents and 85,7% female respondents gave an accurate answers regarding the HIV-infection. However, the overwhelming majority of the study participants, that is, 88,5% men and 98% women, was quite ignorant about the risk of acquiring HIV through saliva and toothbrush of HIV-infected individual. Though that risk is rather insignificant, it is still biologically possible. And this gap in knowledge needs to be filled. As the study showed another point of concern was the fact, that despite the knowledge of HIV transmission risk through unprotected sex about 40% percent of HIVpositive men and 25% of HIV-positive women did not insist on using condoms with their sexual partners. These findings indicate that there are still some aspects about HIV-infection which needed to be clarified and explained through more detailed and specific educational programs.

• Development of a Mobile Image-Based Reminder Application to Support Tuberculosis Treatment in Africa

  Authors: Haji Ali Haji, Hussein Suleman, Ulrike Rivett, Keywords: ICT4D, mobile technology, tuberculosis, visualbased reminder. DOI:10.5281/zenodo.1107738 Abstract: This paper presents the design, development and evaluation of an application prototype developed to support tuberculosis (TB) patients’ treatment adherence. The system makes use of graphics and voice reminders as opposed to text messaging to encourage patients to follow their medication routine. To evaluate the effect of the prototype applications, participants were given mobile phones on which the reminder system was installed. Thirty-eight people, including TB health workers and patients from Zanzibar, Tanzania, participated in the evaluation exercises. The results indicate that the participants found the mobile image-based application is useful to support TB treatment. All participants understood and interpreted the intended meaning of every image correctly. The study findings revealed that the use of a mobile visualbased application may have potential benefit to support TB patients (both literate and illiterate) in their treatment processes.

• Evaluation of the Microscopic-Observation Drug-Susceptibility Assay Drugs Concentration for Detection of Multidrug-Resistant Tuberculosis

  Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi, Keywords: Isoniazid, MODS assay, MDR-TB, Rifampin. DOI:10.5281/zenodo.1092962 Abstract: New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P