REVIEW | doi:10.20944/preprints202308.2059.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: M.tb pathogenesis; MDR-TB; XDR-TB; drug tolerance; new approaches
Online: 30 August 2023 (11:20:12 CEST)
Antibiotics have played a crucial role in the reduction of TB incidence globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline of antibiotic development, and different economic and social conditions. In this review, we summarise recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasise that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throught the community.
REVIEW | doi:10.20944/preprints202309.0778.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Bedaquiline (BDQ); Delamanid (DLM); Xpert MTB; Tuberculosis; TB infection; Latent TB; TB Vaccines; TB Preventive Treatment
Online: 13 September 2023 (07:53:31 CEST)
In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.
ARTICLE | doi:10.20944/preprints202305.0493.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: treatment outcomes; DR-TB; MDR-TB; TB-HIV co-infection; treatment success rate
Online: 8 May 2023 (09:36:25 CEST)
An essential metric for determining the efficacy of tuberculosis (TB) control programs is the evaluation of TB treatment outcomes. Assessing treatment outcomes is fundamental to facilitating the End TB Strategy set target. Clinic records from 457 patients with DR-TB were examined for data collection while 101 patients were followed up prospectively. Data were analyzed using Stata version 17.0. The odds ratio and 95% confidence interval were calculated to check the association between variables. P ≤ 0.05 was con-sidered statistically significant. Of the 427 participants, 65.8% had successful treatment whilst 34.2% had unsuccessful TB treatment. A total of 61.2% and 39% of the HIV-positive and HIV-negative participants had a successful TB treatment whilst 66% and 34% of both HIV-negative and positive participants had unsuccessful TB treatment. From 101 patients that were followed up, smokers had longer treatment outcomes compared to non-smokers. In the study with HIV/TB co-infection, men predominated. HIV and tuberculosis co-infection made therapy difficult with unfavorable effects on TB management. The treatment success rate (65.8%) is lower than the WHO threshold standard with a high proportion of patients lost to follow-up. The co-infection of tuberculosis and HIV resulted in undesirable treatment outcomes. Strengthening TB surveillance and control is recommended.
ARTICLE | doi:10.20944/preprints201905.0225.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: GeneXpert; TB Expert Panel; Smear Negatives; Clinically Diagnosed TB; TB DOTS; Chest X-ray
Online: 17 May 2019 (11:18:34 CEST)
Setting A high proportion of notified tuberculosis cases in the Philippines are clinically diagnosed (63%) as opposed to bacteriologically confirmed. Better understanding of this phenomenon is required to improve tuberculosis control. Objectives To determine the percentage of Smear Negative Presumptive Tuberculosis patients that would be diagnosed by GeneXpert; compare clinical characteristics of patients diagnosed as tuberculosis cases; and review the impact that the current single government physician and a reconstituted Tuberculosis Diagnostic committee (Expert Panel) may have on tuberculosis over-diagnosis. Design This is a cross-sectional study of 152 patients 15-85 years old with two negative Direct Sputum Smear Microscopy results, with abnormal chest X-ray who underwent GeneXpert testing and review by an Expert Panel. Results 31% (48/152) of the sample were Xpert positive. 93% (97/104) of GeneXpert negatives were clinically diagnosed by a Single Physician. Typical symptoms and X-ray findings were higher in bacteriologically confirmed tuberculosis. When compared to GeneXpert results, the Expert panel’s sensitivity for active tuberculosis was high (97.5%, 39/40) but specificity was low (40.2%, 35/87). Conclusion Using the GeneXpert would increase the level of bacteriologically confirmed tuberculosis substantially among presumptive Tuberculosis. An Expert panel will greatly reduce over-diagnosis usually seen when a decision is made by a Single Physician.
BRIEF REPORT | doi:10.20944/preprints202106.0341.v2
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Impact of COVID on TB; TB Notification in India; Integrated TB COVID Activity; Threats and Opportunity during COVID; Initiatives to improve TB Surveillance; TB Surveillance during COVID Pandemic
Online: 22 June 2021 (14:05:04 CEST)
Introduction: Due to COVID-19 pandemic, performance of many program has been declined and Tuberculosis (TB) program is not an exception. TB case detection and notification has been recognized as one of worst hit area. The objective of this study was to explore the TB notification status of India during this pandemic and explore options to mitigate the issue. Methods: A secondary data analysis was performed on open source TB notification database of India. Relevant literature review was done to find out remedies based on the different initiative taken by different states of India. Results: In 2020, total TB notification decreased in all the states in comparison to 2019. The percentage of loss in the country was 34%. Private TB notification also decreased in 2020 in all the states except in Jharkhand. The percentage of loss in private TB notification in the country was 35%. Notification started declining in the month of February 2020 and it was lowest in the month of April-2020. The trend of notification began to improve since May 2020 when the States started taking innovative initiatives like Integrated TB Covid Case Search. Conclusion: Due to the ongoing COVID-19 pandemic the notifications of TB cases declined noticeably which has a serious implication in terms of silent spread within household and community. But the picture can be improved with integrated approach for TB-COVID case finding and management.
ARTICLE | doi:10.20944/preprints202311.0155.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: TB preventive treatment; UNHLM; End TB; TPT; 3HP; Bangladesh
Online: 2 November 2023 (09:58:42 CET)
Background: The UNHLM pledged to enroll 30 million in TB preventive treatment (TPT) by 2022, necessitating TPT expansion to all at TB risk. We assessed uptake and completion of a 12-dose, weekly isoniazid-rifapentine (3HP) TPT regimen. Methods: Between February 2018 - March 2019 in Dhaka, community-based TPT using 3HP targeted household contacts of 883 confirmed drug-sensitive pulmonary TB patients. Adhering to WHO guidelines, contacts underwent active TB screening before TPT initiation. Results: Of 3,193 contacts who advised health facility visits for screening, 67% (n=2,149) complied. Among these, 1,804 (84%) received chest X-rays. Active TB was diagnosed in 39 (2%) contacts; they commenced TB treatment. Over 97% of 1,216 contacts began 3HP TPT, with completion rates higher among females, those with more education and income, non-slum residents, and those without 3HP-related adverse events. Adverse events, mainly mild, occurred in 5% of participants. Conclusions: The 3HP weekly regimen, with its short duration, self-administered option, and minimal side effects, achieved satisfactory completion rates. A community-focused 3HP TPT approach is feasible, scalable nationally, and aligns with UNHLM targets.
ARTICLE | doi:10.20944/preprints202311.1903.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antimicrobial peptide; Mycobacterium tuberculosis; Diagnosis; Spot synthesis; Substitution Analysis; TB; anti TB compound
Online: 29 November 2023 (15:19:12 CET)
Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.
ARTICLE | doi:10.20944/preprints202206.0141.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Acinetobacter baumannii; XDR; IMP-1; VIM-2; NDM-1; VAP; ICU; Hospital-acquired infections
Online: 9 June 2022 (10:58:13 CEST)
A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.
CASE REPORT | doi:10.20944/preprints202308.1607.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: tuberculosis; disseminated TB; low-income setting
Online: 23 August 2023 (09:15:57 CEST)
Disseminated or military tuberculosis (TB) is defined as the presence of at least two non-contiguous sites of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation and spread of a latent focus or due to iatrogenic origin. Disseminated TB represents a life-threatening condition, especially in at-risk children and when the diagnosis and treatment are delayed. We report on a case of a 3-year old boy who presented with long-lasting unrecognised disseminated TB that was successfully managed in a low-resource setting.
ARTICLE | doi:10.20944/preprints202304.0083.v3
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: drug-resistant TB; heteroresistance; mutations; spoligotyping
Online: 9 June 2023 (15:36:21 CEST)
Drug-resistant tuberculosis (DR-TB) is still a major public health concern in South Africa. Mutations in M. tuberculosis can cause varying levels of phenotypic resistance to anti-TB medications. There have been no prior studies on gene mutations and the genotyping of DR-TB in the rural Eastern Cape Province; hence we aimed to identify DR-TB mutations, genetic diversity and allocated lineages among patients in this area. Using Xpert® MTB/RIF, we assessed the rifampin-resistance of sputum samples collected from 1157 patients suspected of having tuberculosis. GenoType MTBDR plus VER 2.0 was used for the detection of mutations causing resistance to anti-TB medications. The next step was to spotlight type 441 isolates. The most prevalent rifampin resistance-conferring mutations were in rpoB codon S531L, in INH-resistant strains, katG gene at codon S315TB and the inhA gene at codon C-15TB had highest mutations; 54.5% and 24.7%, respectively. In addition, 24.6% of strains showed mutations in both the rpoB and inhA genes, while 69.9% of strains showed mutations in both the katG and rpoB genes. Heteroresistance was seen in 17.9% of all cases in the study. According to spoligotyping analysis, Beijing families predominated. Investigating the evolutionary lineages of M. tuberculosis isolates can be done using the information provided by the study's diversity of mutations. In locations where these mutations have been discovered, decision-making regarding standardization of treatment regimens or individualized treatment may be aided by the detection frequency of rpoB, katG, and inhA mutations in various study areas.
ARTICLE | doi:10.20944/preprints202304.0202.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: model developement; TB– HIV integrated model; TB and HIV; model; quantitative and qualitative data
Online: 11 April 2023 (05:39:06 CEST)
Few studies have examined the pros and cons of integrated TB and HIV service delivery in public healthcare facilities, and even fewer have proposed conceptual models for improved integration. This study intends to fill that vacuum by outlining the development of a facility-based paradigm for integrating TB, HIV and patients services. The design of the proposed model were in stages that involved the evaluation of existing TB-HIV integration model and synthesis of both quantitative and qualitative data from the study sites which were selected public healthcare facilities at both rural and peri-urban settings in Oliver Reginald (O.R) Tambo District Municipality in Eastern Cape, South Africa. Secondary data on 2009-2013 TB-HIV clinical outcomes were obtained from multiple sources for quantitative analysis. Qualitative data involved focus group discussions among patient and heath care staff, which was thematically analysed. The development of a possibly better model and validation of this model show that the district's health system was reinforced by the model's guiding principles, which placed a strong emphasis on inputs, processes, outcomes, and integration effects.The model is adaptable to different healthcare delivery systems but will require support from healthcare stakeholders and professionals to be successful.
ARTICLE | doi:10.20944/preprints202308.0004.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Tuberculosis; TB case notification; Spatiotemporal; Oromia; Ethiopia
Online: 1 August 2023 (03:45:40 CEST)
Tuberculosis (TB) is a major public health concern in low and middle-income countries including Ethiopia. This study aimed to assess the spatiotemporal distribution and identify TB risk factors in Ethiopia's Oromia region. Descriptive and spatiotemporal analyses were conducted. Bayesian spatiotemporal modeling was employed to identify covariates that accounted for variability and spatiotemporal distribution of TB. A total of 206,278 new pulmonary TB cases were reported in the Oromia region between 2018 and 2022, with the lowest annual TB case notification (96.93 per 100,000 population) reported in 2020 (i.e., during the COVID-19 pandemic) and the highest TB case notification (106.19 per 100,000 population) reported in 2019. Substantial spatiotemporal variations in the distribution of notified TB case notifications were observed at zonal and district levels with most of the hotspot areas detected in the northern and southern parts of the region. The spatiotemporal distribution of notified TB incidence was positively associated with different ecological variables. The findings of this study indicated that preventive measures considering socio-demographic and health system factors can be targeted to high-risk areas for effective control of TB in the Oromia region. Further studies are needed to develop effective strategies for reducing the burden of TB in hotspot areas.
ARTICLE | doi:10.20944/preprints202208.0425.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: bovine tuberculosis; TB; attenuation; genomes; immunopathogenesis; SNPs
Online: 25 August 2022 (07:18:29 CEST)
Mycobacterium tuberculosis variant bovis (MBO) has one of the widest known mammalian host ranges, including humans. Despite characterization of this pathogen in the 1800s, and whole genome sequencing of a UK strain (AF2122) nearly two decades ago, the basis of its host specificity and pathogenicity remains poorly understood. Recent experimental calf infection studies show that MBO strain Ravenel (MBO Ravenel) is attenuated in the cattle host. In the present study, experimental infections were performed to define attenuation and whole genome sequencing completed to identify regions of differences (RD) and single nucleotide polymorphisms (SNPs) to explain the observed attenuation. Comparative genomic analysis of MBO Ravenel against three pathogenic strains of MBO (strains AF2122-97, 10-7428 and 95-1315) was performed. Experimental infection studies on 5 calves each, with either MBO Ravenel or 95-1315, revealed no visible lesions in all 5 animals in the Ravenel group despite robust IFN-γ responses. Out of 486 polymorphisms in the present analysis, 173 were unique to MBO Ravenel among the strains compared. A high-confidence subset of 9 unique SNPs were missense mutations in genes with annotated functions impacting 2 major MBO survival and virulence pathways: 1) Cell wall synthesis & transport [espH (A103T), mmpL8 (V888I), aftB (H484Y), eccC5 (T507M), rpfB (E263G)], and 2) Lipid metabolism & respiration [mycP1(T125I), pks5 (G455S), fadD29 (N231S), fadE29 (V360G)]. These substitutions likely contribute to the observed attenuation. Results from experimental calf infections and the functional attributions of polymorphic loci on the genome of MBO Ravenel provide new insights into the strain’s genotype-disease phenotype associations.
REVIEW | doi:10.20944/preprints202305.0979.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Tuberculosis; ESAT-6; ESX-1; virulence factors; T7SS; PhoPR signal transduction; host-pathogen interactions; TB vaccines; TB diagnosis
Online: 14 June 2023 (04:33:00 CEST)
Mycobacterium tuberculosis (Mtb) the causative agent of human tuberculosis (TB) is one of the most successfully adapted-human pathogens. Human-to-human transmission occurs at high rates through aerosols containing bacteria, but the pathogen evolved prior to the establishment of crowded populations. Mtb has developed a particular strategy to ensure persistence in the host until an opportunity for transmission arise. It has refined its lifestyle to obviate the need for virulence factors such as capsules, flagella, pilli, or toxins to circumvent mucosal barriers. Instead, the pathogen uses host macrophages, where it establishes intracellular niches, for its migration into the lung parenchyma and other tissues and for the induction of long-lived latency in granulomas. Finally, at the end of the infection cycle Mtb induces necrotic cell death of macrophages to escape to extracellular milieu and instructs a strong inflammatory response required for progression from latency to disease and transmission. Common to all these events is ESAT-6, one of the major virulence factors secreted by the pathogen. This review highlights the recent advances in understanding the role of ESAT-6 in hijacking macrophage function to establish a successful infection and transmission and its use as a target for the development of diagnostic tools, and vaccines.
ARTICLE | doi:10.20944/preprints202309.0825.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Tuberculosis (TB); emphysema; Latent Tuberculosis Infection (LTBI); NHANES
Online: 13 September 2023 (07:14:58 CEST)
(1) Background: A history of TB is a known risk factor for long-term respiratory impairment affecting lung functions in both restrictive and obstructive lung disease. (2) Methods: We analyzed data from the NHANES 1 Epidemiologic Follow-up Study (NHEFS), a longitudinal study conducted on non-institutionalized adult US population, ages 25-74 years. Approximately 93 percent (n=13,383) of the cohort was successfully traced by the end of the survey period and was available for analysis. The final adjusted model included age groups, gender, family income, lifetime smoking, BMI, and frequency of alcohol consumption as potential confounders. (3) Results: Estimated hazards ratio of developing Emphysema during follow-up in individuals that had a past diagnosis of TB was 54% lower (95% CI = 0.35, 0.61) as compared to individuals with no past TB, after controlling for potential confounders and using proportional hazards regression appropriate to the complex sample design. The association, however, was not statistically significant (HR = 0.862, p-value = 0.38) when only self-reported history of TB was considered as the exposure. (4) Conclusion: Tuberculosis (self-reported or LTBI) was strongly (but inversely) associated with Emphysema incidence. The association was not statistically significant with only self-reported history of TB as exposure.
ARTICLE | doi:10.20944/preprints202308.0224.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Keywords: Model; Drug resistance TB, Collaboration and Integration
Online: 3 August 2023 (08:17:13 CEST)
Infectious illnesses have always posed a threat to human health, with tuberculosis (TB) being a major concern. The use of various medications and antibiotics in the fight against such illnesses has led to the emergence of drug-resistant infectious diseases, which have become increasingly dif-ficult to manage as medical and scientific research has advanced. Inadequate medical infrastruc-ture, incorrect treatment practices that exacerbate resistance patterns, and transmission within communities and healthcare facilities are the main factors contributing to the spread of drug-resistant TB. Though treating individuals with multiple drug resistance (MDR) and extreme drug resistance (XDR) strains is challenging, early identification of resistance and the imple-mentation of a well-designed treatment regimen can result in a cure. Community-based inter-ventions that address socioeconomic barriers to adherence can also enhance treatment outcomes. While there have been few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations has been developed. This paradigm seeks to bridge the gap by facilitating the exchange of knowledge among healthcare professionals (HCP) in healthcare facilities (HCF), diagnostic laboratories (DL), and research institutes (RI), particularly for underprivileged communities in the Eastern Cape. The model guide will also monitor and evaluate TB management plans
ARTICLE | doi:10.20944/preprints202307.1138.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: HIV infection; Tuberculous meningitis; TB-DOTS; Mycobacterium tuberculosis
Online: 18 July 2023 (08:44:17 CEST)
: Background and objectives: One of the most severe symptoms of extrapulmonary tuberculosis (TBEP) is tuberculous meningitis (TBM) which is linked to significant morbidity and high mortality. It is well recognized that HIV-positive people are more likely to develop TBEP, including TBM, especially if they have severe immunodeficiencies. Material and methods: We conducted a retrospective clinical study based on hospital medical records of the diagnosed patients with HIV/AIDS and Tuberculous Meningitis in North-eastern Romania, hospitalized at "Sf. Parascheva" Clinical Hospital of Infectious Diseases from Iasi. We aim to highlight the profile and the caracteristics of the HIV/AIDS and Tuberculous Meningitis coinfection cases. The time frame under study was from January 1st, 2010, to December 1st, 2022. Results: Our Center has a total number of patients on record of 1692. Patients co-infected with HIV- TB were 195 of which 19 cases were HIV- TBM coinfection and it was more common in women. From this total, 6 cases were late presenters and 13 patients were already in the center's records with a deficient immunological viral status, non-compliant, and non-adherent to antiretroviral therapy. The average age in the study group was 27 years old. The mean admission day number was 17.73 days. CSF findings (qualitative and quantitaitve examination, biochemestry) were in accordance with the literature. Conclusions: The key to the management of the HIV-positive patient is the multidisciplinary approach and access to antiretroviral therapy. We must find and eliminate obstacles affecting patients and the healthcare system. In order to increase ART uptake among HIV-infected TB patients and to put an end to the TB and HIV epidemics.
ARTICLE | doi:10.20944/preprints202109.0314.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: GeneXpert; MDR-TB; Prevalence; River Nile State; Sudan
Online: 17 September 2021 (12:41:23 CEST)
Background: World Health Organization (WHO) estimates that there were 558000 new cases with resistance to Rifampicin, of which 82% had multidrug-resistant tuberculosis (MDR-TB). Objectives: We aimed to identify the prevalence of MDR-TB in River Nile state, Sudan, and the risk factors contributing to its occurrence. Methods: This was a descriptive cross-sectional hospital-based study involved 200 specimens taken from patients suspected of having MDR-TB tested using an automated GeneXpert assay. Results: Results of GeneXpert assay showed that the presence of Mycobacterium tuberculosis in 81 (40.5%), and out of 81 positive test results there were 13 (16%) had MDR-TB. Additionally, 7 cases of MDR-TB were previously treated which represented about (53%) of MDR patients, the remaining 6 MDR-TB patients were new cases and represented (47%) of MDR-TB patients. Moreover, there were 4 MDR-TB patients who had a history of contact with MDR-TB patients. Conclusion: Prevalence of MDR-TB in River Nile State, Sudan was 16%, which is greater than WHO estimation for Sudan (10.1%). The results revealed that the main risk factor to develop MDR-TB was a history of contact with MDR-TB, so adherence to treatment and social awareness about the spread of MDR-TB are crucial preventive measures.
ARTICLE | doi:10.20944/preprints202106.0355.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: TB; Treatment Adherence; Private Sector; Defaulter; LTFU; THALI
Online: 14 June 2021 (11:45:29 CEST)
Objective: In India, yearly, estimated one million TB cases are missing from notification, mostly from private sector. The large number of patients in private sector has raised concerns for suboptimal quality of care. This study was conducted to find out the treatment adherence status among the private TB patients and factors associated with poor adherence.Data Source: Secondary project data, obtained through adherence monitoring house visit by NGO workers. Data collected by reviewing different records available with the patients & data was entered into the CommCare HQ, an open-source mobile platform designed for data collection.Methods: Descriptive observational study.Results: Default rate among private patients was 5%. Commonest reasons stated for being a defaulter were ‘Medicine is not good’ (30%), ‘Travel’ (28.6%), ‘Cost of treatment’ (21.8%) and ‘Side effects’ (11.6%). Despite best of efforts only 36.9% defaulter could be retrieved. Higher default rate was associated with 15-59 years age, males, earning member of the family, addiction, DR-TB, continuation phase of treatment, previous history of TB, presence of symptoms and inability to walk.Conclusion: Privately treated TB patients are vulnerable to non-adherence. Once defaulted, it is difficult to retrieve them. Economically productive age group is at higher risk of being defaulter. Strict adherence monitoring for private TB patients and extensive advocacy communication & social mobilization program in the community, workplaces and institutions is a need of hour.
REVIEW | doi:10.20944/preprints201912.0002.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: tuberculosis (TB); diagnostics; lipoarabinomannan (LAM); urinary test; diagnosis
Online: 2 December 2019 (04:18:41 CET)
Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker which can be detected in urine, an easily collected sample. This review discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next-generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.
ARTICLE | doi:10.20944/preprints201909.0123.v1
Subject: Medicine And Pharmacology, Tropical Medicine Keywords: Active case findings; Tuberculosis; TOUCH Agent; High TB burden area; TB Surveillance; 4S Screening; THALI Project; SORT IT; Operational Research
Online: 11 September 2019 (13:30:30 CEST)
Background: Active case finding for TB was implemented in selected sixty high TB burden wards of Kolkata, India. Community volunteers called TOUCH agents (TAs) identified and referred presumptive TB patients (PTBPs) to health facilities for TB diagnosis and treatment. We aimed to describe the ‘care cascade’ of PTBPs identified during July to December, 2018 and to explore the reasons for attrition as perceived by TAs and PTBPs. Methods: An explanatory mixed methods study with quantitative phase of cohort study using routinely collected data followed by descriptive qualitative study with in-depth interviews was conducted. Results: Of the 3, 86,242 individuals enumerated, 1132 (0.3%) PTBPs were identified. Only 713 (63.0%) PTBPs visited referred facility for TB diagnosis. TB was diagnosed in 177 (24.8%) and the number needed to screen for one TB was 2,183 individuals. The potential reasons for low yield were stigma and apprehension about TB, distrust about TA, wage loss for attending health facilities and substance abuse among PTBPs. Conclusion: The yield of ACF was suboptimal with low PTBP identification rate and high attrition rate. Interviewing each individual for symptoms of TB and supporting PTBPs for diagnosis through sputum collection and transport can be adopted to improve the yield.
ARTICLE | doi:10.20944/preprints202201.0165.v1
Subject: Computer Science And Mathematics, Probability And Statistics Keywords: HIV/TB co-infected Mortality; Residential Variations; Multilevel Logistic Regression
Online: 12 January 2022 (13:34:06 CET)
The purpose of this study was to identify the factors that affect the mortality among adult HIV/TB co-infected patients and to see the nutritional difference among mortality in residence level. Retrospective cohort studies of 417 patients which fulfill our criteria were included. Multilevel logistic regression models were used. MLwiN and SPSS software are used to estimate the parameter. The variance of the random factor in the empty model was significant which indicates that there were residential differences in TB-HIV co-infected mortality and it shows multilevel analysis was an appropriate approach for further analysis. The prevalence of HIV/TB co-infected patients' death was 12.9% in study time. Functional status, age of patients, WHO clinical stages, nutritional status, CD4 counts, regimen, and BMI were found to be significant determinants of HIV/TB co-infected mortality. In our study, patients with the bedridden category of functional status, the fourth stages of WHO clinical stages (stage IV), patients with higher age, patients whose treatments were second-line regimen and low CD4 cell counts were more at risk of death. The study also revealed that; poor nutritional status increased the risk of mortality among HIV/TB co-infected patients and it varies among the residence of the patients (rural area were more at risk).
ARTICLE | doi:10.20944/preprints202109.0283.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Tuberculosis; Delay in diagnosis; Treatment outcomes; Internally displaced TB patients.
Online: 16 September 2021 (12:26:00 CEST)
Human displacement is on the rise globally, and the increase in the burden of tuberculosis (TB) is also attributed to migrations worldwide. A significant number of such displacement occur in regions with considerably higher areas of TB burden. Displacements may delay in TB diagnosis and treatment, which possibly will lead to TB transmission among healthy individuals. In this study, we assessed the association of existing determinants after a protracted internal displacement of people with the delay in TB diagnosis and treatment outcomes. A cross-sectional study was conducted on internally displaced TB patients registered at selected health facilities in three urban districts of Pakistan from March 2019 to February 2020. The univariate and multivariate logistic regression model was used to assess the delay in diagnosis and treatment outcomes. IDPs with delay in initiation of treatment beyond 30 days were at high possibility of unsuccessful TB treatment outcomes (adjusted odds ratio AOR,2.60; 95% CI 1.06-6.40). Analysis of factors that affect health seeker behavior and timely treatment showed a significant association (p<0.05) in-between age group 55-65 years (AOR, 2.66; 95% CI 1.00-7.07), female patients (AOR, 2.42; 95% CI 1.21-4.81), visited non-formal health provider (AOR, 8.81; 95% CI 3.99-19.46), self-medication (AOR, 2.72; 95 % CI 1.37-5.37), poor knowledge of TB (AOR, 11.39; 95% CI 3.31-39.1), and perceived stigma (AOR, 8.81; 95% CI 3.99-19.4). Prolong delay in treatment was associated with unfavorable treatment outcomes among IDPs, more specifically. As migrants and IDPs are more likely to experience an interruption in care due to overall exclusion from social and health care services. Therefore, it is imperative to understand the barriers in providing public health care services, particularly in preventing and treating TB.
ARTICLE | doi:10.20944/preprints201701.0035.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: QuantiFERON-TB Gold In-Tube test; pulmonary tuberculosis; sensitivity; specificity
Online: 9 January 2017 (03:58:00 CET)
The value of QuantiFERON in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 128 cases with active PTB and 128 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. Their IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; P < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.
ARTICLE | doi:10.20944/preprints201805.0040.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: anti-TB activity; catalysis; cyclization; olivacine; palladium; pyrido[4,3-b]carbazoles
Online: 2 May 2018 (12:54:38 CEST)
The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant anti-TB activity with an MIC90 value of 1.5 μM.
ARTICLE | doi:10.20944/preprints202004.0448.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: acetyleugenol; Acacia nilotica; anti-tuberculosis; Serine/Threonine kinases; multi-drug resistant TB
Online: 24 April 2020 (14:12:33 CEST)
Acetyleugenol is a phytochemical compound with broad effect against infectious diseases and tumors. Here, we extracted, characterized and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)―a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial pathogenic isolates with best activity against Proteus sp., Salmonella typhi, Staphylococcu aureus, and Streptococcus pneumonia, which showed similar or better zone of inhibition to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogs were subjected to molecular docking experiments against two potential tuberculosis drug targets―MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores comparing to the acetyleugenol. The indole analogs EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with –11.08 and –10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analog has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogs with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.
ARTICLE | doi:10.20944/preprints202305.1050.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Kyrgyz Republic; TB presumptive; failure; operational research; SORT IT; key population; private sector
Online: 15 May 2023 (14:09:10 CEST)
Until 2021, in the Kyrgyz Republic, tuberculosis(TB) was diagnosed and treated only in the public sector. With funding support of the STOP-TB partnership, the private providers in four regions of the country and Bishkek city were mapped, trained and incentivized to screen for, identify presumptive TB patients, and refer them to the public facilities for diagnosis and treatment. In this study, we describe the cascade of care of such patients. This was a cohort study involving secondary analysis of routine data. Of 79,352 patients screened during February 2021-March 2022, 2,511(3%) had presumptive TB, of whom, 903(36%) were not tested for TB [pre-diagnostic loss-to-follow-up]. A total of 323(13%) patients were diagnosed as TB, of whom, 42(13%) were not started on treatment [pre-treatment loss-to-follow-up]. Among 257 patients eligible for outcome assessment, 197(77%) had treatment success, 29(11%) were lost-to-follow-up, 13(5%) died, 4(2%) had treatment failure and 14(5%) were not evaluated. While this donor-funded, pioneering initiative was successful in engaging the private sector, we recommend the national TB programme to scale-up the initiative nationally with dedicated budgets, activities and plans to monitor the progress. Qualitative research is urgently needed to understand the reasons for the gaps in the care cascade.
ARTICLE | doi:10.20944/preprints202211.0401.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: TB-HIV integration; Challenges and barriers; Patients; O.R Tambo District; Eastern Cape; South Africa
Online: 22 November 2022 (03:08:13 CET)
Abstract: Tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics in South Africa have been closely related and persistent, posing a significant burden for healthcare provision. We explored the patients perspectives on challenges and barriers of scaling up TB and HIV integrated services. A descriptive cross-sectional study applying a qualitive research approach was used. Through focus group discusssions (FGDs), we interviewed 29 patients accessing TB and HIV services at the study sites which were selected at primary health care (PHC) clinics in the O.R Tambo district in Eastern Cape, South Africa. Anonymised data was analysed using both content and thematic analysis technique. Challenges and barriers identified included a lack of health education about TB and HIV; an inadequate counselling for antiretroviral drugs (ARVs) and HIV; a lack of awareness of the National TB control program; and poor quality of services provided by the health care facilities. These findings suggest that the O.R. Tambo district needs to strengthen its TB-HIV integration immediately. Keywords: TB-HIV integration; Challenges and barriers; Patients; O.R Tambo District; Eastern Cape; South Africa
ARTICLE | doi:10.20944/preprints202008.0634.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: bovine TB; risk factors; disease control; animal health policy; veterinary epidemiology; evidence-based policy
Online: 28 August 2020 (11:25:31 CEST)
Bovine tuberculosis (bTB) outbreaks, caused by Mycobacterium bovis infection, are a costly animal health challenge. Understanding factors associated with the duration of outbreaks, known as breakdowns, could lead to better disease management policy development. We undertook a retrospective observational study (2012-2018) and employed Finite Mixture Models (FMM) to model the outcome parameter, and to investigate how factors were associated with duration for differing subpopulations identified. In addition to traditional risk factors (e.g. herd size, bTB history), we also explored farm geographic area, parcels/farm fragmentation, metrics of intensity via nitrogen loading, and whether herds were designated controlled beef finishing units (CBFU) as potential risk factors for increased duration. The final model fitted log-normal distributions, with two latent classes (k) which partitioned the population into a subpopulation around the central tendency of the distribution, and a second around the tails of the distribution. The latter subpopulation included longer breakdowns of policy interest. Increasing duration was positively associated with recent (<3 yrs) TB history and the number of reactors disclosed, (log) herd size, beef herd-type relative to other herd types, number of land parcels, area, and being designated a controlled finishing unit (“feedlot”), and having high annual inward cattle movements within the “tails” subpopulation. Breakdown length was negatively associated with year of commencement of breakdown (i.e. a decreasing trend) and non-significantly with the organic nitrogen produced on the farm (N kg/hectare), a measure of stocking density. The latter finding may be due to confounding effects with herd size and area. Most variables contributed only moderately to explaining variation in breakdown duration, that is, they had moderate size effects on duration. Herd-size and CBFU had greater effect sizes on the outcome. The findings contribute to evidence-based policy formation in Ireland.
REVIEW | doi:10.20944/preprints201910.0362.v1
Subject: Computer Science And Mathematics, Probability And Statistics Keywords: tuberculosis (TB); human immunodeficiency virus (HIV); Acquired Immune Deficiency Syndrome (AIDS); World Health Organization (WHO); panel data; poisson; negative binomial; regression
Online: 31 October 2019 (04:33:45 CET)
Tuberculosis cause of death worldwide and the leading cause from a single infectious agent, ranking above Human immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). The aim of this study is to ascertain the trend of tuberculosis prevalence and the effect of HIV prevalence onl Tuberculosis case in some West African countries from 2000 to 2016 using count panel data regression models. The data used annual HIV and Tuberculosis cases spanning from 2000 to 2016 extracted from online publication of World health Organization (WHO). Panel Poisson regression model and Negative binomial regression model for fixed and random effects were used to analyzed the count data, the result revealed a positive trend in TB cases while increased in HIV cases leads to increase in TB cases in West African countries. Among the competing models used in this study, Panel Negative Binomial Regression Model with fixed effect emerged the best model with log likelihood value of -1336.554. This study recommended that Government and NGOs need more strategies to fight against HIV menace in West Africa as this will in turn reduced TB cases in West Africa.
ARTICLE | doi:10.20944/preprints202308.0906.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Bedaquiline; Oral bioavailability; Solubility; Quality by design (QbD); Pseudo-ternary; Self-nanoemulsifying drug delivery systems (SNEDDS); Multi-drug resistance tuberculosis (MDR-TB)
Online: 11 August 2023 (07:09:51 CEST)
Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, USFDA has given expedited approval to bedaquiline (BDQ), as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis but due to poor solubility desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of Bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of Bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88±2.1 nm with a zeta potential of 21.16 mV. In vitro, studies showed enhanced drug release with a high degree of stability at 25 ± 2 ºC & 60 ± 5 % and 40 ± 2 ºC & 75± 5 %. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.
ARTICLE | doi:10.20944/preprints202305.1948.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Kyrgyz Republic; drug-sensitive pulmonary TB; electronic register system; paper-based records; completeness; concordance; treatment initiation; treatment outcomes; SORT IT; operational research
Online: 29 May 2023 (02:49:28 CEST)
This study evaluated the effectiveness of an electronic system for managing drug-sensitive pulmonary tuberculosis patients in the Kyrgyz Republic. This was a cohort study using programmatic data. The study included patients registered on the paper-based system in 2019 and the electronic system between June 2021 and May 2022. Data was taken from 302 individuals from the electronic system for completeness and concordance in comparison with the paper-based system. The study showed that for most variables the completeness and concordance was 85.3%-93.0% and was lowest for non-mandatory fields such as medication side effects (26.8% vs 13.6%). No significant difference was observed in time taken from symptom onset to diagnosis and treatment initiation between the two systems. However, the electronic system had a significantly higher percentage of patients who initiated treatment on the same day of diagnosis (80.3% vs. 57.1%). The proportion with successful outcomes was similar in both groups, but the electronic system had a significantly lower proportion of patients with outcomes that were not evaluated or recorded (4.8% vs. 14.3%, p < 0.001). The study highlights the potential advantages of implementing an electronic TB register system for improving records. We advocate for similar studies in other regions in Kyrgyz Republic.
ARTICLE | doi:10.20944/preprints201910.0342.v1
Subject: Computer Science And Mathematics, Probability And Statistics Keywords: Tubercolusis (TB); Poisson Autoregressive (PAR); Poisson Exponentially Weighted Moving Average Model (PEWMA); Hepatitis; Human Immunodeficiency Virus (HIV); Acquired Immune Deficiency Syndrome (AIDs)
Online: 29 October 2019 (15:51:16 CET)
The research work examined the trend of HIV/AIDS, Tuberculosis, and Hepatitis diseases in Plateau state. Annual data from 2003 to 2018 was collected from the department of biostatistics at Plateau State Specialist Hospital (PSSH), Jos. The methods of analysis used are the Poisson Autoregressive Model (PAR(1)) and the Poisson Exponentially Weighted Moving Average Model (PEWMA). The results revealed a significant annual decrease of 23.9% and 4% in Tuberculosis and HIV/AIDS respectively. Furthermore, the results showed a significant annual increase of 46% in Hepatitis. The PEWMA model used revealed that TB increased by 0.02% when there is an increase in HIV but not significant, while Hepatitis significantly aggravates TB by at least 0.24%. Also, there is a significant rise in HIV by 0.85% when TB increases but Hepatitis has no such effect on HIV. Lastly, PEWMA model indicated a rise of 0.5% in Hepatitis cases when there is an increase in TB, but a surge in HIV has no such effect on Hepatitis cases in Jos. The study recommended that fight against TB should be intensified since TB cases significantly affect both HIV and Hepatitis in Jos, Nigeria.