The high household costs associated with tuberculosis (TB) diagnosis and treatment can create barriers to access and adherence, highlighting the urgency of achieving the World Health Organization's ...End TB Strategy target that no TB-affected households should face catastrophic costs by 2020.
To estimate the occurrence of catastrophic costs associated with TB diagnosis and treatment and to identify socioeconomic indicators associated with catastrophic costs in a setting where TB control strategies have been implemented effectively.
In this cross-sectional study, 455 patients with TB in the Chennai metropolitan area of South India who were treated under the TB control program between February 2017 and March 2018 were interviewed. Patients were interviewed by trained field investigators at 3 time points: at the initiation of treatment, at the end of the intensive phase of treatment, and at the end of the continuation phase of treatment. A precoded interview schedule was used to collect information on demographic, socioeconomic, and clinical characteristics and direct medical, direct nonmedical, and indirect costs. Data analysis was performed from August 2018 to November 2019.
Direct, indirect, and total costs to patients with TB. Catastrophic costs associated with TB were defined as costs exceeding 20% of the household's annual income. A binary response model was used to determine the factors that were significantly associated with catastrophic costs.
Of 455 patients with TB interviewed, 205 (53%) were aged 19 to 45 years (mean SD age, 38.4 16.0 years), 128 (33%) were female, 72 (19%) were illiterate, 126 (33%) were employed, and 186 (48%) had a single earning member in the family (percentages are based on the 384 patients who were interviewed through the end of the continuation phase of treatment). Sixty-one percent of patients (234 patients) had pulmonary smear positive TB. The proportion of patients with catastrophic costs was 31%. Indirect costs contributed more toward catastrophic cost than did direct costs. Multivariate logistic regression analysis found that unemployment (adjusted odds ratio, 0.2; 95% CI, 0.1-0.5; P < .001) and higher annual household income (Rs 1-200 000, adjusted odds ratio, 0.4; 95% CI, 0.2-0.7; P = .004; Rs >200 000, adjusted odds ratio, 0.2; 95% CI, 0.1-0.5; P < .001) were associated with a decreased likelihood of experiencing catastrophic costs.
Despite the implementation of free diagnostic and treatment services under a national TB control program, TB-affected households had a high risk of catastrophic costs and further impoverishment. There is an urgent demand to provide additional financial protection for patients with TB.
Plasma proteins are known to interfere the drug metabolism during therapy. As limited information is available regarding the role of plasma proteins in HIV drug resistance during ART in HIV/AIDS ...patients, the present study aimed to identify and characterize the differentially expressed plasma proteins in the drug resistant and drug respondent groups of HIV-1 infected patients with > 6 years of first line ART.
Four-drug resistant (treatment failure) and four-drug respondent (treatment responder) patients were selected for plasma proteomic analysis based on viral load and drug resistance associated mutations from a cohort study designed on the first line ART patients who were enrolled in the antiretroviral therapy center, Sarojini Naidu Medical College, Agra, India from December 2009 to November 2016. After depleting high abundant proteins, plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3-10. Spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein data base using the internal Mascot. Gene ontology study was completed through STRING v.11 and Panther15.0.
Out of eight spots from 2D gel samples analyzed by MALDITOF/TOF, two proteins were found to have significant score (> 56) after Flex analysis. These two proteins were identified to be apolipoprotein A1 and serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. Apolipoprotein-A1 and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes.
Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and ...isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013-2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of
mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB.
Optimal recovery of mycobacteria from the contaminated liquid culture is a challenge. While alternative methods have been suggested to reduce the rate of contamination in the BACTEC MGIT 960 system, ...reprocessing the contaminated liquid culture improves recovery of Mycobacterium tuberculosis. Among 793 MGIT cultures raised from as many sputum specimens after primary decontamination by the standard NaLC-NaOH method, valid results were available for 687 (86.6%) as 106 (13.4%) were contaminated. Reprocessing and reculturing of the contaminated cultures increased valid results to 739 (93.2%) and reduced the contamination rate to 6.8%. Both values were statistically significant. Recovery of the Mycobacterium tuberculosis complex increased from 45.6% to 48.4%. Valid negative results were available for an additional 3.4%. The method may be adopted to reduce the rate of contamination and to improve the valid culture results for mycobacteria.
Background
Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3‐ and 4‐month regimens containing moxifloxacin in a randomised clinical trial ...in pulmonary TB (PTB) patients in South India.
Methods
New, sputum‐positive, adult, HIV‐negative, non‐diabetic PTB patients were randomised to 3‐ or 4‐month moxifloxacin regimens moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) or to a control regimen (2H3R3Z3E3/4R3H3) C. The 4 test regimens were 3R7H7Z7E7M7 M3, 2R7H7Z7E7M7/2R7H7M7 M4, 2R7H7Z7E7M7/2R3H3M3 M4‐I or 2R7H7Z7E7M7/2R3H3E3M3 M4‐IE. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post‐treatment. The primary end point was TB recurrence post‐treatment.
Results
Of 1371 patients, randomised, modified intention‐to‐treat (ITT) analysis was done in 1329 and per‐protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. ‘Favourable’ response at end of treatment was 96–100% in the moxifloxacin regimens and 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI −3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4‐I and M4‐IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification.
Conclusion
The 4‐month daily moxifloxacin regimen M4 was found to be equivalent and as safe as the 6‐month thrice‐weekly control regimen.
Contexte
La réduction de la durée du traitement de la tuberculose (TB) est une priorité de recherche. Nous avons testé l'efficacité et la sécurité de schémas thérapeutiques contenant de la moxifloxacine pendant 3 et 4 mois dans un essai clinique randomisé chez des patients atteints de TB pulmonaire (PTB) dans le sud de l’Inde.
Méthodes
De nouveaux patients PTB, adultes, non diabétiques, positifs pour les expectorations, VIH négatifs ont été randomisés pour des schémas thérapeutiques contenant de la moxifloxacine pendant 3 mois ou 4 mois moxifloxacine (M), isoniazide (H), rifampicine (R), pyrazinamide (Z), l'éthambutol (E) ou pour un régime témoin (2H3R3Z3E3/4R3H3) C. Les 4 régimes de l’essai étaient 3R7H7Z7E7M7 M3, 2R7H7Z7E7M7/2R7H7M7 M4, 2R7H7Z7E7M7/2R3H3M3 M4‐I ou 2R7H7Z7E7M7/2R3H3E3M3 M4‐IE. Le traitement a été directement observé. Les évaluations cliniques et bactériologiques ont été effectuées mensuellement au cours du traitement et durant 24 mois après le traitement. Le critère d'évaluation principal était la récidive de la TB après le traitement.
Résultats
Des 1.371 patients randomisés, une analyse en intention de traiter (ITT) modifiée a été effectuée sur 1.329 et une analyse par protocole (PP) sur 1.223 patients. Le régime M3 a été interrompu en raison de taux élevés de récidive de la TB. La réponse «favorable» à la fin du traitement était de 96 à 100% dans les bras moxifloxacine et 93% dans le bras témoin. Parmi ceux‐ci, la récidive de la TB est survenue chez 4,1% dans le schéma M4 et chez 4,5% dans le schéma témoin et a démontré une équivalence dans une marge de 5% (IC95%: −3,68, 4,55). Des résultats similaires ont été observés dans l'analyse ITT modifiée. Les taux de récidive de la TB dans les schémas M4‐I et M4‐IE n'ont pas montré d'équivalence avec le schéma témoin. 16 (1,4%) des 1.087 patients dans les régimes à moxifloxacine ont nécessité une modification du traitement.
Conclusion
Le régime quotidien de moxifloxacine pendant 4 mois M4 s'est avéré équivalent et aussi sûr que le régime témoin de trois fois par semaine pendant 6 mois.
Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1)-infected individuals. However, only 10-30% of infected individuals produce broadly neutralizing ...antibodies (bNAbs). Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN) ability (1). In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Three of the five individuals (NAB033, NAB059, and NAB065) demonstrated a significant increase (
< 0.05) in potency. Interestingly, two of the three samples also showed a significant increase in CD4 binding site-specific antibody response, maintained stable CD4+ T cell counts (>350 cells/mm
) and continued to remain ART-naïve for more than 10 years after initial diagnosis, implying a strong clinical correlation with the development and evolution of broadly neutralizing antibody response against HIV-1.
Geographically, most tuberculosis (TB) cases in 2018 were reported from India. This TB burden is compounded by MDR-TB and XDR-TB. The strategies for the management and control of TB in the community ...depend on an understanding of the mode of spread of the different strains of TB isolates in the community. To determine the distribution and trends of M. tb strains over the time period in the community due to treatment, we carried out the present study on changes over two decades. Design/Methods. A total of 1218 M. tb isolates (year: 2001–2018) from Tiruvallur, India, were genotyped by spoligotyping after DNA extraction and subjected to anti-TB drug susceptibility testing for the first-line anti-TB drugs. Results. On analysis with the SpolDB4 database, majority (2001–2003: 53.32% and 2015–2018: 46.3%) of the isolates belonged to East African Indian (EAI) lineage, and the orphans designated in comparison to SpolDB4 stood 33% among 2001–2003 strain collection and 46.3% among 2015–2018 strain collection. 10.2% (2001–2003) and 9.26% (2015 to 2018) of isolates were monoresistant to isoniazid (H). MDR strains were less common among EAI strains (3.2%) compared to non-EAI strains (10.32%). Conclusions. EAI is the most predominant lineage in Tiruvallur, despite the presence of highly transmissible lineages like Beijing for the last two decades. The prevalence of MDR-TB is below the national average of 2-3% among the new TB cases in the last two decades. The reason can be attributed to the well-established nature of the locally circulating strains in this region which are not associated with drug resistance.
C–C motif chemokine ligand 2, a gene that codes for a protein involved in inflammation. Certain SNPs in the CCL2 gene have been studied for their potential associations with susceptibility to various ...diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in CCL2 may influence the immune response to Mycobacterium leprae infection.
To investigate the association of the C–C motif chemokine ligand-2 single nucleotide polymorphisms with leprosy.
CCL2 single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for CCL2 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for CCL2 -2134 T>G, 325 leprosy and 288 controls for CCL2 -1549 A>T SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β were estimated in sera samples and correlated with CCL2 genotypes.
The frequency of the GCT (-2518 A>G, -362 G>C, -2134 T>G) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-2518A>G, p = 0.53), (-362 G>C, p = 0.01), (-2134 T>G, p = 0.10)}. G allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). GG genotype (p = 0.008) and G allele at -2518 (p = 0.030) of the CCL 2 gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -2518 AA and AG genotypes (p = 0.0001).
G allele and GG genotype at the CCL2 -2518 site are associated with a risk of ENL reactions.
•Host directed therapy is an adjunctive to the immune response of a host to fight against infections.•Xenophagy is a form of selective autophagy that helps the host in reducing the burden of ...infectious microorganisms.•Infected Immune cells, non-classically activate vitamin D3, which express antimicrobial peptides.•Activated vitamin D3 and trace elements enhance the xenophagic pathway and eliminate the infection.
According to the WHO report 2019, Tuberculosis (TB) is an ancient disease of humanity that is curable. TB has caused significant morbidity and mortality even in 2018. The etiological agent of TB, Mycobacterium tuberculosis (MTB) exploits its virulence factors to escape from host immunity and therapeutic drugs. Host Directed Therapy (HDT) is an adjunctive therapy where repurposed drugs, small molecules, vitamins, cytokines, and monoclonal antibodies are used to overcome the pathogen exploited pathways in the host. One of the HDTs, i.e. induction of autophagy is a highly regulated intracellular self-degradative process in which pathogens are sequestered in double-layered autophagosomes and targeted to the lysosome for degradation. Apart from the pathogen clearance, autophagy involves the release of nutrients during starvation, removal of damaged organelles and aggregated proteins, antigen presentation, tumor suppression, and anti-aging mechanisms. Xenophagy is a type of selective autophagy against microbes induced by ubiquitin receptors (p62/SQSTM1, NDP52, NBR1, OPTN, Parkin and Smurf proteins) after pathogen recognition. ULK1/2, Beclin-1, ATG5-ATG12-ATG16 L and LC-II-PE complexes along with two nutrient-sensing protein complexes, mTOR and AMPK activate autophagy mechanisms to limit infection. Pattern Recognition Receptors (PRRs) such as TLR2, recognize lipopolysaccharide (LPS) of MTB and triggers vitamin D3 activating enzymes. Activated vitamin D3 induces the synthesis of antimicrobial peptide, LL-37, which further enhances xenophagy. Apart from vitamin D, few micronutrients such as zinc and iron also regulate autophagy. In this review, we discuss current knowledge, advances and perspectives of autophagy against TB.
•Pooled testing has the advantage of reducing several constraints of individual testing.•We put forth various pooled testing models that are presumed to be practical for SARS-CoV-2 testing and ...evaluate their resource efficiency at different prevalence rates.•Pooling can be implemented in low prevalence settings, especially for community surveillance.
SARS-CoV-2 has surged across the globe causing the ongoing COVID-19 pandemic. Systematic testing to facilitate index case isolation and contact tracing is needed for efficient containment of viral spread. The major bottleneck in leveraging testing capacity has been the lack of diagnostic resources. Pooled testing is a potential approach that could reduce cost and usage of test kits. This method involves pooling individual samples and testing them ‘en bloc’. Only if the pool tests positive, retesting of individual samples is performed. Upon reviewing recent articles on this strategy employed in various SARS-CoV-2 testing scenarios, we found substantial diversity emphasizing the requirement of a common protocol. In this article, we review various theoretically simulated and clinically validated pooled testing models and propose practical guidelines on applying this strategy for large scale screening. If implemented properly, the proposed approach could contribute to proper utilization of testing resources and flattening of infection curve.
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