Project description:BackgroundMultidrug-resistant tuberculosis (MDR-TB) in HIV infected individuals is a serious threat to global efforts to combat tuberculosis. Inconsistent findings on the association between HIV infection and MDR-TB were present in many studies. We aimed to review existing data on the relationship between HIV infection and MDR-TB systematically to assess the contribution of HIV on MDR-TB worldwide. We also investigated the patterns of MDR-TB by age, country-wise income, study designs, and global regions.MethodsWe utilized PubMed, Google Scholar, and ScienceDirect databases to select eligible studies for meta-analysis that were published between January 12,010, and July 30, 2020. The random-effects model was used to obtain the pooled odds ratio of the crude association between HIV and MDR-TB with a 95% confidence interval. We investigated the potential publication-bias by checking funnel plot asymmetry and using the Egger's test. Moreover, we assessed the heterogeneity using the I2 statistic. Sensitivity analysis was performed based on sample size and adjustment factors. The protocol was registered with PROSPERO-CRD42019132752.ResultsWe identified 1603 studies through a database search, and after subsequent eliminations we selected 54 studies including 430,534 TB patients. The pooled odds of MDR-TB was 1.42 times higher in HIV-positive patients than HIV-negative patients (OR=1.42,CI=1.17-1.71, I2=75.8%). Subgroup analysis revealed that the estimated pooled odds for South-East Asian countries was 1.86, which is the highest in WHO regions (OR=1.86,CI=1.30-2.67, I2=0.00%), followed by Europe and Africa. The effect estimate was found to be higher for primary MDR-TB (OR=2.76,CI=1.70-4.46, I2=0.00%). There was also a trend towards increased odds of MDR-TB for HIV patients older than 40 years (OR=1.56,CI=1.17-2.06). The association was found to be significant in high-burden TB countries (OR=1.75, CI=1.39-2.19) and in high-income countries (OR=1.55, CI=1.06-2.27).ConclusionSuch findings indicate that HIV infection raises the risk of MDR-TB, and after contrasting it with the results of the earlier pooled study, it appeared to be an upward risk trend. Moreover, we found that the risk is the highest in the South-East Asian region. A balanced allocation of resources is needed to halt both primary and secondary MDR-TB, particularly in HIV infected people with 40 years of age and older.
Project description:Multidrug-resistant (MDR) bacteria pose a significant clinical threat to human health, but the development of antibiotics cannot meet the urgent need for effective agents, especially those that can kill persisters and biofilms. Here, we reported that nigericin showed potent bactericidal activity against various clinical MDR Gram-positive bacteria, persisters and biofilms, with low frequencies of resistance development. Moreover, nigericin exhibited favorable in vivo efficacy in deep-seated mouse biofilm, murine skin and bloodstream infection models. With Staphylococcus aureus, nigericin disrupted ATP production and electron transport chain; cell death was associated with altered membrane structure and permeability. Obtaining nigericin-resistant/tolerant mutants required multiple rounds of challenge, and, cross-resistance to members of several antimicrobial classes was absent, probably due to distinct nigericin action with the GraSR two-component regulatory system. Thus, our work reveals that nigericin is a promising antibiotic candidate for the treatment of chronic or recurrent infections caused by Gram-positive bacteria.
Project description:Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I2, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13-89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.
Project description:To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches.We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization's portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses.Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01-1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38-1.13), for death RR: 1.01 (95% CI: 0.67-1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48-2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models.Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings.
Project description:IntroductionTransgender individuals are at risk for HIV. HIV risks are dynamic and there have been substantial changes in HIV prevention (e.g., pre-exposure prophylaxis [PrEP]). It is thus time to revisit HIV prevalence and burden among transgender individuals. The objective of this systematic review and meta-analysis was thus to examine worldwide prevalence and burden of HIV over the course of the epidemic among trans feminine and trans masculine individuals.MethodsWe conducted an updated systematic review by searching PsycINFO, PubMed, Web of Science, and Google Scholar, for studies of any research design published in in a peer-reviewed journal in any language that reported HIV prevalence among transgender individuals published between January 2000 and January 2019. Two independent reviewers extracted the data and assessed methodological quality. We then conducted a meta-analysis, using random-effects modelling, to ascertain standardized prevalence and the relative burden of HIV carried by transgender individuals by country and year of data collection, and then by geographic region. We additionally explored the impact of sampling methods and pre-exposure prophylaxis (PrEP).ResultsBased on 98 studies, overall standardized HIV prevalence over the course of the epidemic, based on weights from each country by year, was 19.9% (95% CI 14.7% - 25.1%) for trans feminine individuals (n = 48,604) and 2.56% (95% CI 0.0% - 5.9%) for trans masculine individuals (n = 6460). Overall OR for HIV infection, compared with individuals over age 15, was 66.0 (95% CI 51.4-84.8) for trans feminine individuals and 6.8 (95% CI 3.6-13.1) for trans masculine individuals. Prevalence varied by geographic region (13.5% - 29.9%) and sampling method (5.4% - 37.8%). Lastly, PrEP effects on prevalence could not be established.ConclusionTrans feminine and trans masculine individuals are disproportionately burdened by HIV. Their unique prevention and care needs should be comprehensively addressed. Future research should further investigate the impact of sampling methods on HIV prevalence, and monitor the potential impact of PrEP.
Project description:BackgroundMultidrug-resistant (MDR) bacteria are the main cause of lower respiratory tract infections (LRTIs) with high mortality. The purpose of this study is to identify the risk factors associated with MDR by performing a systematic review and meta-analysis.MethodsPubMed, EMBASE (via Ovid), and Cochrane Library were systematically searched for studies on the risk factors for MDR bacteria in LRTIs as of November 30, 2019. Literature screening, data abstraction, and quality assessment of the eligible studies were performed independently by two researchers.ResultsA total of 3,607 articles were retrieved, of which 21 articles representing 20 cohort studies published in English were included after title/abstract and full-text screening. Among the 21 articles involving 7,650 patients and 1,360 MDR organisms, ten reported the risk factors for MDR Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), ten for MDR GNB, and one for MDR GPB. The meta-analysis results suggested that prior antibiotic treatment, inappropriate antibiotic therapy, chronic lung disease, chronic liver disease and cerebral disease, prior MDR and PA infection/colonization, recent hospitalization, longer hospitalization stay, endotracheal tracheostomy and mechanical ventilation, tube feeding, nursing home residence, and higher disease severity score were independent risk factors for MDR bacteria.ConclusionsThis review identified fourteen clinical factors that might increase the risk of MDR bacteria in patients with LRTIs. Clinicians could take into account these factors when selecting antibiotics for patients and determine whether coverage for MDR bacteria is required. More well-designed studies are needed to confirm the various risk factors for MDR bacteria in the future.
Project description:The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)50/MIC90 values for AMXT-1501 in the range of 3.13-12.5 μM (2.24-8.93 μg /mL), including for methicillin-resistant Staphylococcus aureus (MRSA), CR Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of S. aureus and Enterococcus faecalis. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.
Project description:Multidrug-resistant pathogens pose a serious threat to human health. For decades, the antibiotic vancomycin has been a potent option when treating Gram-positive multidrug-resistant infections. Nonetheless, in recent decades, we have begun to see an increase in vancomycin-resistant bacteria. Here, we show that the nuclear factor-kappa B (NF-κB) inhibitor N-[3,5-Bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (IMD0354) was identified as a positive hit through a Caenorhabditis elegans-methicillin-resistant Staphylococcus aureus (MRSA) infection screen. IMD0354 was a potent bacteriostatic drug capable of working at a minimal inhibitory concentration (MIC) as low as 0.06 µg/mL against various vancomycin-resistant strains. Interestingly, IMD0354 showed no hemolytic activity at concentrations as high as 16 µg/mL and is minimally toxic to C. elegans in vivo with 90% survival up to 64 µg/mL. In addition, we demonstrated that IMD0354's mechanism of action at high concentrations is membrane permeabilization. Lastly, we found that IMD0354 is able to inhibit vancomycin-resistant Staphylococcus aureus (VRSA) initial cell attachment and biofilm formation at sub-MIC levels and above. Our work highlights that the NF-κB inhibitor IMD0354 has promising potential as a lead compound and an antimicrobial therapeutic candidate capable of combating multidrug-resistant bacteria.
Project description:Introduction HIV-positive status disclosure for children is challenging for family members, guardians, and healthcare professionals. Disclosure is very challenging, particularly for children, yet no systematic synthesis of evidence accurately measures HIV-positive status disclosure in children. This systematic review and meta-analysis study aimed to quantify the national prevalence of pediatric HIV-positive status disclosure in Ethiopia and identify factors associated with HIV-positive status disclosure. Method We systematically searched PubMed, EMBASE, Web of Science databases, and google scholar for relevant published studies. Studies published in the English language and conducted with cohort, case-control, and cross-sectional designs were eligible for the review. The primary and secondary outcomes of the study were HIV-positive status disclosure and factors associated with HIV-positive status disclosure, respectively. The quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. A random effect- model was used to estimate the pooled prevalence of HIV-positive status disclosure. Heterogeneity and publication bias of included studies was determined using I2 and Egger’s test, respectively. Result From 601 records screened, nine relevant studies consisting of 2,442 HIV-positive children were included in the analysis. The overall pooled prevalence of HIV-positive status disclosure among children living with HIV/AIDS in Ethiopia was 31.2% (95% CI [23.9–38.5]). HIV-negative status of caregivers (AOR: 2.01; 95% CI [1.28–3.18]), long duration on ART (greater than 5 years) (AOR: 3.2; 95% CI [1.77–5.78]) and older age of the child (>10 years) (AOR: 7.2; 95% CI [4.37–11.88]) were significantly associated with HIV-positive status disclosure. Conclusion Low prevalence of pediatric HIV-positive status disclosure was observed in Ethiopia. The longer duration of ART, the HIV-negative status of the caregiver, and older age greater than 10 years were the predictors of pediatric HIV-positive status disclosure. Health system leaders and policymakers shall design training and counseling programs for healthcare professionals and caregivers to enhance their awareness about HIV-positive status disclosure. Trial registration This review was registered under PROSPERO and received a unique registration number, CRD42019119049.
Project description:BackgroundMultidrug-resistant (MDR) bacteria are a global health threat, notably in low- and middle-income countries. The aim of this review was to estimate the prevalence of multidrug-resistant bacteria in healthcare and community settings in West Africa.MethodsIn accordance with PRISMA guidelines, we searched PubMed, CINAHL, African Index Medicus, and other databases for studies published from 2010 onward. Data on MDR bacterial prevalence, study characteristics, and infection types were extracted and analyzed via R software. Subgroup analyses were performed to explore differences in prevalence across infection settings and sample types.ResultsOut of the 5,320 articles identified, 50 studies from 13 West African countries met the inclusion criteria, with the majority from Nigeria (34%) and Ghana (22%). Among the 35,820 bacteria isolated in these studies, gram-negative bacteria (GNB), particularly Escherichia coli and Klebsiella sp., were the most frequently isolated species, accounting for 63.3% of the bacteria. The overall prevalence of MDR bacteria was 59% (95% CI: 48-69%), with significant heterogeneity between studies (I² = 98%, p < 0.001). Subgroup analysis revealed a 7% increase in MDR bacteria prevalence from the first five-year period to the last two five-year periods, and a greater prevalence of MDR bacteria in nosocomial infections (65%, 95% CI: 45-81%) than in community-acquired infections (53%, 95% CI: 31-74%). The prevalence of MDR bacteria in mixed infection settings was 58% (95% CI: 44-71%). The MDR prevalence was highest in the urine samples (72%, 95% CI: 57-84%) and superficial skin samples (69%, 95% CI: 29-92%), whereas it was lowest in the nasopharyngeal samples (26%, 95% CI: 21-33%).ConclusionThe high prevalence of MDR bacteria in West Africa underscores the need for strengthened infection control measures, improved surveillance, and stricter antibiotic use policies. Enhanced regional collaboration is essential to mitigate the spread of AMR in both healthcare and community settings.Prospero registration numberCRD42023470363.