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.
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.
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.
Abstract: In this study, due to the recurrence of bovine tuberculosis, in the same areas, the risk factors for the disease were determined and evaluated at the local level. This study was carried out in 32 farms where the disease was detected in the district and center of Samsun province in 2014. Predetermined risk factors, such as farm, environmental and economic risks, were investigated with the survey method. It was predetermined that risks in the three groups are similar to the risk variables of the disease on the global scale. These risk factors that increase the susceptibility of the infection must be understood by the herd owners. The risk-based contagious disease management system approach should be applied for bovine tuberculosis by farmers, animal health professionals and public and private sector decision makers.
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.
Abstract: Performing culture and characterization of mycobacteria in low resource settings like Nigeria is a very difficult task to undertake because of the very few and limited laboratories carrying out such an experiment; this is a largely due to stringent and laborious nature of the tests. Hence, a rapid, simple and accurate test for characterization is needed. The “SD BIOLINE TB Ag MPT 64 Rapid ®” is a simple and rapid immunochromatographic test used in differentiating Mycobacteria into Mycobacterium tuberculosis (NTM). The 100 sputa were obtained from patients suspected to be infected with tuberculosis and presented themselves to hospitals for check-up and treatment were involved in the study. The samples were cultured in a class III Biosafety cabinet and level III biosafety practices were followed. Forty isolates were obtained from the cultured sputa, and there were identified as Acid-fast bacilli (AFB) using Zeihl-Neelsen acid-fast stain. All the isolates (AFB positive) were then subjected to the SD BIOLINE Analyses. A total of 31 (77.5%) were characterized as MTBC, while nine (22.5%) were NTM. The total turnaround time for the rapid assay was just 30 minutes as compared to a few days of phenotypic and genotypic method. It was simple, rapid and reliable test to differentiate MTBC from NTM.
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.
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.
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.
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.
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.
Abstract: Tuberculosis (TB) remains a leading cause of
infectious mortality. It is primarily transmitted by the respiratory
route, individuals with active disease may infect others through
airborne particles which releases when they cough, talk, or sing and
subsequently inhale by others. In order to study the effect of the
Bacilli Calmette-Guerin (BCG) vaccine after vaccination of TB
patient, a Vaccinated Susceptible Infected and Recovered (VSIR)
mathematical model is being developed to achieve the desired
objectives. The mathematical model, so developed, shall be used to
quantify the effect of BCG Vaccine to protect the immigrant young
adult person. Moreover, equations are to be established for the
disease endemic and free equilibrium states and subsequently utilized
in disease stability analysis. The stability analysis will give a
complete picture of disease annihilation from the total population if
the total removal rate from the infectious group should be greater
than total number of dormant infections produced throughout
infectious period.
Abstract: We present a deterministic model which describes
the dynamics of tuberculosis in Algerian population where the
vaccination program with BCG is in place since 1969 and where
the WHO recommendations regarding the DOTS (directly-observed
treatment, short course) strategy are in application. The impact
of an intervention program, targeting recently infected people
among all close contacts of active cases and their treatment to
prevent endogenous reactivation, on the incidence of tuberculosis,
is investigated. We showed that a widespread treatment of latently
infected individuals for some years is recommended to shift from
higher to lower equilibrium state and thereafter relaxation is
recommended.
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
Abstract: Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.
Abstract: Pyrazinamide (PZA) is among the first-line pro-drugs in the tuberculosis (TB) combination chemotherapy used to treat Mycobacterium tuberculosis. Numerous reports have suggested that hepatotoxicity due to pyrazinamide in patients is due to inappropriate dosing. It is, therefore necessary to develop sensitive and reliable techniques for determining the PZA metabolic profile of diagnosed patients promptly and at point-of-care. This study reports the determination of PZA based on nanobiosensor systems developed from disuccinimidyl octanedioate modified Cytochrome P450-2E1 (CYP2E1) electrodeposited on gold substrates derivatised with (poly(8-anilino-1-napthalene sulphonic acid) PANSA/PVP-AgNPs nanocomposites. The rapid and sensitive amperometric PZA detection gave a dynamic linear range of 2µM to 16µM revealing a
limit of detection of 0.044µM and a sensitivity of 1.38µA/µM. The Michaelis-Menten parameters; KM, KM app and IMAX were calculated to be 6.0µM, 1.41µM and 1.51x10-6 A, respectively, indicating a nanobiosensor suitable for use in serum.
Abstract: M. paratuberculosis is a slow growing mycobactin dependent mycobacterial species known to be the causative agent of Johne’s disease in all species of domestic ruminants worldwide. JD is characterized by gradual weight loss; decreased milk production. Excretion of the organism may occur for prolonged periods (1 to 2.5 years) before the onset of clinical disease. In recent years researchers focus on identification a specific antigen of MAP to use in diagnosis test and preparation of effective vaccine. In this paper, for production of polyclonal antibody against proteins of Mycobacterium avium paratuberculosis cell well a rabbit immunization at a certain time period with antigen. After immunization of the animal, rabbit was bleeded for producing enriched serum. Antibodies were purification with ion exchange chromatography. For exact measurement of interaction, western blotting test was used that this study demonstrated sharp bands appears in nitrocellulose paper and specific bands were 50 and 150 KD molecular weight. These were indicating immunodominant proteins.
Abstract: Modelling is a widely used tool to facilitate the evaluation of disease management. The interest of epidemiological models lies in their ability to explore hypothetical scenarios and provide decision makers with evidence to anticipate the consequences of disease incursion and impact of intervention strategies.
All models are, by nature, simplification of more complex systems. Models that involve diseases can be classified into different categories depending on how they treat the variability, time, space, and structure of the population. Approaches may be different from simple deterministic mathematical models, to complex stochastic simulations spatially explicit.
Thus, epidemiological modelling is now a necessity for epidemiological investigations, surveillance, testing hypotheses and generating follow-up activities necessary to perform complete and appropriate analysis.
The state of the art presented in the following, allows us to position itself to the most appropriate approaches in the epidemiological study.
Abstract: Tuberculosis (TB) is a bacterial infectious disease caused by the obligate human pathogen, Mycobacterium tuberculosis. Multidrug-resistant tuberculosis (MDR-TB) is a global reality that threatens tuberculosis control. Resistance to antibiotic Rifampicin, occurs in 95% of cases through nucleotide substitutions in an 81-bp core region of the rpoB i.e; beta subunit of DNA dependant RNA polymerase. In this paper, we studied the Rifampicin-rpoB receptor interactions In silico. First, homology modeling was performed to obtain the three dimensional structure of Mycobacterium rpoB. Sixty analogs of Rifampicin were prepared using Marvin sketch software. Both original Rifampicin and the analogs were docked with rpoB and energy values were obtained. Out of sixty analogs, 43 analogs had lesser energy values than conventional Rifampicin and hence are predicted to have greater binding affinity to rpoB. Thus, this study offers a route for the development of Rifampicin analogs against multi drug resistant Mycobacterium rpoB.
Abstract: Kwashiorkor is one of nutritional problem in
Indonesia, which lead to decrease immune system. This condition
causes susceptibility to infectious disease, especially tuberculosis.
Development of new tuberculosis vaccine will be an important
strategy to eliminate tuberculosis in kwashiorkor. Previous research
showed that 38-kDa Mycobacterium tuberculosis protein is one of the
potent immunogen. However, the role of oral immunization with 38-
kDa Mycobacterium tuberculosis protein to the number of
lymphocytes in the rat model of kwashiorkor is still unknown. We
used kwashiorkor rat model groups with 4% and 2% low protein diet.
Oral immunization with 38-kDa Mycobacterium tuberculosis protein
given with 2 booster every week. The lymphocytes number were
measured by flowcytometry. There was no significant difference
between the number of lymphocytes in the normal rat group and the
kwashiorkor rat groups. It may reveal the role of 38-kDa
Mycobacterium tuberculosis protein as a potent immunogen that can
increase the lymphocytes number from kwashiorkor rat model same
as normal rat.