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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269065

RESUMO

BackgroundCoronavirus disease 2019 (COVID-19) is also associated with other co-morbidities among with previous and current pulmonary tuberculosis (PTB). PTB is a risk factor for COVID-19, both in terms of severity and mortality, regardless of human immunodeficiency virus (HIV) status. However, there is less information available on COVID-19 associated with PTB in point of view incidence and mortality rates in sub-Saharan Africa (SSA) as a high burden TB region. This systematic review served to provide data synthesis of available evidence on COVID-19/PTB incidence and case fatality rates, and mortality rate found in clinical and post-mortem COVID-19/PTB diagnostics in SSA. MethodsWe conducted a systematic electronic search in the PubMed, Medline, Google Scholar, Medrxix and COVID-19 Global literature on coronavirus disease databases for studies including COVID-19 associated with PTB in sub-Saharan Africa. The main outcomes were the proportion of people with COVID-19 associated to current /or previous PTB and the case fatality associated to COVID-19/PTB. The combination method was based on methodological similarities in the included random effect model studies using Prometa 3 software. We further undertook sensitivity analysis and meta-regression. ResultsFrom the 548 references extracted by the literature search, 25 studies were selected and included in the meta-analysis with a total of 191, 250 COVID-19 infected patients and 11, 452 COVID-19 deaths. The pooled COVID-19/PTB incidence was 2% [1%-3%] and mortality of 10% [4%-20%]. The pooled estimates for case fatality rate among COVID-19/PTB were 6% [3%-11%] for clinical PTB diagnostic and 26% [14%-48%] for post-mortem PTB diagnostic. Meta-regression model including the effect sizes and cumulative COVID-19 cases (P= 0.032), HIV prevalence (P= 0.041) and TB incidence (P= 0.002) to explained high heterogeneity between studies. ConclusionAs a summary, the incidence of TB associated with COVID-19 and case fatality rates are higher in SSA. However, COVID-19 associated to TB may be underreported in the studies conducted in SSA as the post-mortem TB diagnostic was higher. Large-scale cohort studies that adequately clear tool on previous and/or current TB diagnostic tools are required to confirmed COVID-19/TB incidence and case fatality in SSA. Review registrationPROSPERO (CRD42021233387)

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268505

RESUMO

ObjectivesTo assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT). MethodsIndividuals [≥]5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard. ResultsOut of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration [≤] 3days versus [≤] 7days. Agreement between nasal and nasopharyngeal Ag-RDT was 99.4%. ConclusionsThe STANDARD Q Ag-RDT showed high specificity. Sensitivity was, however, below the WHO recommended minimum requirement of [≥] 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling. Highlights- Prospective study on real-world diagnostic performance of nasal and nasopharyngeal SD Biosensor STANDARD Q COVID-19 Ag Test in 2131 participants in a rural African setting - The sensitivity of the STANDARD Q COVID-19 Ag Test was below the World Health Organization requirement of [≥] 80% but met the specificity requirement of [≥]97%. - Sensitivity was higher in the following subpopulations: persons with symptoms [≤]3 days, and Ct value < 25. - In head-to-head comparison nasal and nasopharyngeal sampling had comparable sensitivity and specificity and an overall test agreement of 99.4%, indicating that the more convenient nasal sampling could be used for SARS-CoV-2 rapid antigen tests. - 24 of the 2131 participants with COVID-19 symptoms had pulmonary tuberculosis with a positive Xpert Ultra test on sputum.

3.
Clin Infect Dis ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35015842

RESUMO

Testing programs for SARS-CoV-2 have relied on high-throughput PCR laboratories and rapid antigen assays to meet diagnostic needs. Both technologies are essential, however issues of cost, accessibility, manufacturing delays and performance have limited their use in low resource settings and contributed to the global inequity in Covid-19 testing. Emerging low-cost, multi-disease point-of-care nucleic acid tests may address these limitations and strengthen pandemic preparedness, especially within primary healthcare where most cases of disease first present. Widespread deployment of these novel technologies will also help close long-standing test access gaps for other diseases, including tuberculosis, HIV, cervical cancer, viral hepatitis and sexually transmitted infections. We propose a more optimized testing framework based on greater use of point-of-care nucleic acid tests together with rapid immunologic assays and high-throughput laboratory molecular tests to improve the diagnosis of priority endemic and epidemic diseases, as well as strengthen the overall delivery of primary healthcare services.

4.
J Korean Med Sci ; 37(3): e20, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35040295

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea. METHODS: We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as 'before-pandemic' and 'during-pandemic' based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment. RESULTS: Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715-1.094). CONCLUSION: The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic's impact on the national TB control project.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35046100

RESUMO

BACKGROUND: Over the last 30 years, South Africa has experienced four 'colliding epidemics' of HIV and tuberculosis, chronic illness and mental health, injury and violence, and maternal, neonatal, and child mortality, which have had substantial effects on health and well-being. Using data from the 2019 Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we evaluated national and provincial health trends and progress towards important Sustainable Development Goal targets from 1990 to 2019. METHODS: We analysed GBD 2019 estimates of mortality, non-fatal health loss, summary health measures and risk factor burden, comparing trends over 1990-2007 and 2007-2019. Additionally, we decomposed changes in life expectancy by cause of death and assessed healthcare system performance. RESULTS: Across the nine provinces, inequalities in mortality and life expectancy increased over 1990-2007, largely due to differences in HIV/AIDS, then decreased over 2007-2019. Demographic change and increases in non-communicable diseases nearly doubled the number of years lived with disability between 1990 and 2019. From 1990 to 2019, risk factor burdens generally shifted from communicable and nutritional disease risks to non-communicable disease and injury risks; unsafe sex remained the top risk factor. Despite widespread improvements in healthcare system performance, the greatest gains were generally in economically advantaged provinces. CONCLUSIONS: Reductions in HIV/AIDS and related conditions have led to improved health since 2007, though most provinces still lag in key areas. To achieve health targets, provincial governments should enhance health investments and exchange of knowledge, resources and best practices alongside populations that have been left behind, especially following the COVID-19 pandemic.

7.
Trop Med Infect Dis ; 7(1)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35051128

RESUMO

As the COVID-19 pandemic surged, lockdowns led to the cancellation of essential health services. As part of our Zero TB activities in Karachi, we adapted our approach to integrate activities for TB and COVID-19 to decrease the impact on diagnosis and linkage to care for TB treatment. We implemented the following: (1) integrated COVID-19 screening and testing within existing TB program activities, along with the use of an artificial intelligence (AI) software reader on digital chest X-rays; (2) home delivery of medication; (3) use of telehealth and mental health counseling; (4) provision of PPE; (5) burnout monitoring of health workers; and (6) patient safety and disinfectant protocol. We used programmatic data for six districts of Karachi from January 2018 to March 2021 to explore the time trends in case notifications, the impact of the COVID-19 pandemic, and service adaptations in the city. The case notifications in all six districts in Karachi were over 80% of the trend-adjusted expected notifications with three districts having over 90% of the expected case notifications. Overall, Karachi reached 90% of the expected case notifications during the COVID-19 pandemic. The collaborative efforts by the provincial TB program and private sector partners facilitated this reduced loss in case notifications.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35063300

RESUMO

BACKGROUND: In the situation where COVID-19 pandemic has placed unprecedented demands and pressure on the health care system, we wanted to analyze how the medical microbiologists of our country were affected. Was it actually an opportunity to showcase the specialty or was it a doom? A debate was organized as a key session in the national e-conference of the Indian Association of Medical Microbiologists, held on 10 December 2020. OBJECTIVES: The objective of the debate was to examine and analyze the various positive as well as negative impacts of COVID-19 on the discipline of the medical microbiology of our country. CONTENT: Before the debate a voting session was conducted to assess the opinion of the audience followed by a very interesting debate where both the speakers presented their view points. The points in favor of the discipline were, mainly up-gradation of the specialty of microbiology in terms of learning, skill development, infrastructure, networking & research opportunities related to COVID-19. While the main points against were, nerve wracking work load without much acknowledgement, performance pressure from hospital administration to maintain rapid turnaround time, and a forceful neglect of all other infectious diseases like tuberculosis and antimicrobial resistance which were the key battle fields of the medical microbiologists. Postgraduate & even undergraduate training programs got completely derailed to their disadvantage. By the end of the debate, it was concluded that COVID-19 was neither a boon nor a bane to the microbiologists. A balanced approach to the problem in hand is required without ignoring the pre-existing infectious diseases in our country. The post debate voting swayed the audience considerably for it to be a bane & the faculty debating for boon had a huge margin to begin with but finally won with a whisker indicating the intensity of the debate.

9.
Curr HIV/AIDS Rep ; 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35064888

RESUMO

PURPOSE OF REVIEW: To describe how mitigation measures against COVID-19 have impacted HIV and TB research in South Africa. RECENT FINDINGS: South Africa has the highest number of COVID-19 (34%) cases in Africa, accounting for 43% of all reported COVID-19-related deaths on the continent. The country accounts for 20% of all people living with HIV and ranked third in the world for new TB infections in 2019. While South Africa's investments in its HIV and TB responses enabled it to pivot rapidly to respond to the emerging COVID-19 epidemic, it negatively impacted the HIV and TB response through temporary suspension of research, diversion of key resources for HIV and TB control, and patient access to health care facilities; the full extent of this has yet to emerge. Success in integrating responses to the colliding epidemics could potentially enhance survival outcomes and ensure gains made to date in HIV and TB are not reversed and we stay on track toward achieving the UN 2030 Sustainable Development Goals.

10.
Environ Sci Technol ; 56(2): 1125-1137, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34985868

RESUMO

Some infectious diseases, including COVID-19, can undergo airborne transmission. This may happen at close proximity, but as time indoors increases, infections can occur in shared room air despite distancing. We propose two indicators of infection risk for this situation, that is, relative risk parameter (Hr) and risk parameter (H). They combine the key factors that control airborne disease transmission indoors: virus-containing aerosol generation rate, breathing flow rate, masking and its quality, ventilation and aerosol-removal rates, number of occupants, and duration of exposure. COVID-19 outbreaks show a clear trend that is consistent with airborne infection and enable recommendations to minimize transmission risk. Transmission in typical prepandemic indoor spaces is highly sensitive to mitigation efforts. Previous outbreaks of measles, influenza, and tuberculosis were also assessed. Measles outbreaks occur at much lower risk parameter values than COVID-19, while tuberculosis outbreaks are observed at higher risk parameter values. Because both diseases are accepted as airborne, the fact that COVID-19 is less contagious than measles does not rule out airborne transmission. It is important that future outbreak reports include information on masking, ventilation and aerosol-removal rates, number of occupants, and duration of exposure, to investigate airborne transmission.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Aerossóis , Surtos de Doenças , Humanos , SARS-CoV-2 , Ventilação
11.
PLoS One ; 17(1): e0262057, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35025938

RESUMO

Respiratory tract infections (RTIs) are extremely common and can cause gastrointestinal tract symptoms and changes to the gut microbiota, yet these effects are poorly understood. We conducted a systematic review to evaluate the reported evidence of gut microbiome alterations in patients with a RTI compared to healthy controls (PROSPERO: CRD42019138853). We systematically searched Medline, Embase, Web of Science, Cochrane and the Clinical Trial Database for studies published between January 2015 and June 2021. Studies were eligible for inclusion if they were human cohorts describing the gut microbiome in patients with an RTI compared to healthy controls and the infection was caused by a viral or bacterial pathogen. Dual data screening and extraction with narrative synthesis was performed. We identified 1,593 articles and assessed 11 full texts for inclusion. Included studies (some nested) reported gut microbiome changes in the context of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (n = 5), influenza (H1N1 and H7N9) (n = 2), Tuberculosis (TB) (n = 4), Community-Acquired Pneumonia CAP (n = 2) and recurrent RTIs (rRTI) (n = 1) infections. We found studies of patients with an RTI compared to controls reported a decrease in gut microbiome diversity (Shannon) of 1.45 units (95% CI, 0.15-2.50 [p, <0.0001]) and a lower abundance of taxa (p, 0.0086). Meta-analysis of the Shannon value showed considerable heterogeneity between studies (I2, 94.42). Unbiased analysis displayed as a funnel plot revealed a depletion of Lachnospiraceae, Ruminococcaceae and Ruminococcus and enrichment of Enterococcus. There was an important absence in the lack of cohort studies reporting gut microbiome changes and high heterogeneity between studies may be explained by variations in microbiome methods and confounder effects. Further human cohort studies are needed to understand RTI-induced gut microbiome changes to better understand interplay between microbes and respiratory health.


Assuntos
Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Infecções Respiratórias/microbiologia , Animais , Bactérias/crescimento & desenvolvimento , Humanos
12.
BMJ Open ; 12(1): e056009, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980628

RESUMO

OBJECTIVES: This study aims to identify levels of adherence to antiretroviral therapy (ART) drugs and factors associated with them in Northwest Ethiopia. We hypothesise that in the era of COVID-19, there would be suboptimal adherence to ART drugs. DESIGN: An observational cross-sectional study was conducted. Factors associated with the level of adherence were selected for multiple logistic regressions at a p value of less than 0.2 in the analysis. Statistically significant associated factors were identified at a p value less than 0.05 and adjusted OR with a 95% CI. SETTING: The study was conducted in one specialised hospital and three district hospitals found in the South Gondar zone, Northwest Ethiopia. PARTICIPANTS: About 432 people living with HIV/AIDS receiving highly active ART in South Gondar zone public hospitals and who have been on treatment for more than a 3-month period participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Levels of adherence to ART drugs and their associated factors. RESULTS: Among 432 study participants, 81.5% (95% CI: 78% to 85.2%) of participants were optimally adherent to ART drugs. Determinants of a low level of adherence: stigma or discrimination (OR=0.4, p=0.016), missed scheduled clinical visit (OR=0.45, p=0.034), being on tuberculosis treatment (OR=0.45, p=0.01), recent CD4 cell count less than 500 cells/mm3 (OR=0.3, p=0.023) and patients who had been on WHO clinical stage III at the time of ART initiation (OR=0.24, p=0.027) were factors significantly associated with adherence to ART drugs. CONCLUSIONS: Level of adherence was relatively low compared with some local studies. The intervention targeted to reduce discrimination, counselling before initiation of treatment and awareness regarding compliance is advised to improve adherence to antiretroviral regimens.


Assuntos
COVID-19 , Infecções por HIV , Estudos Transversais , Etiópia , Infecções por HIV/tratamento farmacológico , Humanos , Adesão à Medicação , SARS-CoV-2
14.
J Telemed Telecare ; : 1357633X211068277, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989631

RESUMO

INTRODUCTION: Due to the growing burden of disease in South Africa, encompassing conditions such as tuberculosis, human immunodeficiency virus, and cancer, the holistic management of affected patients incorporating ototoxicity monitoring is a necessity. However, ototoxicity monitoring in developing countries may be limited due to a lack of resources and inadequate healthcare facilities. Subsequently, the use of tele-audiology may be a revolutionary technique with the potential to provide audiology services to under-served populations with limited access. METHODS: The study aimed to describe the use of tele-audiology services in ototoxicity monitoring through a scoping review of English peer-reviewed articles from June 2009 to June 2020. Seventeen articles were purposively selected from the following databases: PubMed, Science Direct, Taylor and Francis Online, WorldCat, and Google Scholar. Data was extracted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram and results were analyzed using deductive thematic analysis. RESULTS AND DISCUSSION: While a minority of the studies indicated that the cost of implementation and network connectivity within a South African context pose as barriers, most researchers reported that tele-audiology provides a reliable, time-efficient, cost-effective, and easily accessible alternative for ototoxicity monitoring. Hardware including the WAHTS, KUDUwave, and OtoID, along with software such as the TabSINT, Otocalc, uHear, and the hearTest, have proven to be useful for ototoxicity monitoring. A need for further investigations regarding the feasibility of tele-audiology implementation in South Africa is evident. Despite this, it provides audiologists with an opportunity to offer contact-less services during COVID-19, thus, confirming its versatility as an augmentative method for ototoxicity monitoring.

15.
Mini Rev Med Chem ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983348

RESUMO

Evidence from multiple scientific studies suggests that the Bacillus Calmette-Guérin (BCG) vaccine, widely used worldwide as a preventive measure against tuberculosis, also offers cross-protection against other pathogens. This review aimed to gather data from research that studied the mechanisms involved in the immunological protection induced by the BCG vaccine, which may be important in the control of viral infections, such as COVID-19. Through a literature review, we compiled information about the different BCG strains used worldwide, as well as the responses and protection elicited by them. We commented on the mechanisms of immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and we discussed the possibility of cross-protection of different BCG strains on the control of COVID-19. Due to the immunomodulatory properties of BCG, some BCG strains were able to induce an effective cellular immune response and, through epigenetic modifications, activate cells of the innate immune system, such as monocytes, macrophages and natural killer cells, which are crucial for the control of viral infections. Although several vaccines have already been developed and used in an attempt to control the COVID-19 pandemic, some BCG vaccine strains may help stimulate the basal defences against these pathogens and can be used as additional defences in this and future pandemics.

16.
PLoS One ; 17(1): e0262179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35051205

RESUMO

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.

17.
Cells ; 11(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35053318

RESUMO

Oxidized cholesterols, the so-called oxysterols, are widely known to regulate cholesterol homeostasis. However, more recently oxysterols have emerged as important lipid mediators in the response to both bacterial and viral infections. This review summarizes our current knowledge of selected oxysterols and their receptors in the control of intracellular bacterial growth as well as viral entry into the host cell and viral replication. Lastly, we briefly discuss the potential of oxysterols and their receptors as drug targets for infectious and inflammatory diseases.

18.
Int J Mol Sci ; 23(2)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35055170

RESUMO

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb), resulted in almost 1.4 million deaths in 2019, and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes into close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic, innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb-host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional, with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay shows that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows a lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status, determined by factors such as age, might play an important role in determining infection outcome.

19.
JCI Insight ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990408

RESUMO

BACKGROUND: Adenoviral (Ad)-vectored vaccines are typically administered via intramuscular injection to humans, incapable of inducing respiratory mucosal immunity. However, aerosol delivery of Ad-vectored vaccines remains poorly characterized and its ability to induce mucosal immunity in humans is unknown. This phase 1b trial was to evaluate the safety and immunogenicity of human serotype-5 Ad-vectored tuberculosis (TB) vaccine (AdHu5Ag85A) delivered to humans via inhaled aerosol or intramuscular injection. METHODS: 31 healthy, previously BCG-vaccinated adults were enrolled. AdHu5Ag85A was administered by single-dose aerosol using Aeroneb® Solo Nebulizer or by intramuscular (IM) injection. The study consisted of the low dose (LD) aerosol, high dose (HD) aerosol and IM groups. The adverse events were assessed at various times post-vaccination. Immunogenicity data were collected from the peripheral blood and bronchoalveolar lavage samples at baseline and select timepoints post-vaccination. RESULTS: The nebulized aerosol droplets were <5.39µm in size. Both LD and HD of AdHu5Ag85A administered by aerosol inhalation and IM injection were safe and well-tolerated. Both aerosol doses, particularly LD, but not IM, vaccination markedly induced airway tissue-resident memory CD4 and CD8 T cells of polyfunctionality. While as expected, IM vaccination induced Ag85A-specific T cell responses in the blood, the LD aerosol vaccination also elicited such T cells in the blood. Furthermore, the LD aerosol vaccination induced persisting transcriptional changes in alveolar macrophages. CONCLUSIONS: Inhaled aerosol delivery of Ad-vectored vaccine is a safe and superior way to elicit respiratory mucosal immunity. This study warrants further development of aerosol vaccine strategies against respiratory pathogens including TB and COVID-19. TRIAL REGISTRATION: This trial is registered with ClinicalTrial.gov, NCT# 02337270. FUNDING: The Canadian Institutes for Health Research and the Natural Sciences and Engineering Research Council of Canada.

20.
Ear Nose Throat J ; : 1455613211070896, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34974770

RESUMO

Laryngeal tuberculosis is the most frequent granulomatous disease of the larynx and it is prone to be diagnosed as cancer. COVID-19 pandemic caused considerable disruption in tuberculosis service provisions both in the primary care and hospital settings. This report describes a rare case of life-threatening stridor in a patient who presented with an ulceroproliferative laryngeal mass later confirmed as laryngeal tuberculosis. Urgent tracheostomy was performed. The patient's sputum and the computed tomography of the chest revealed a pulmonary, as well as laryngeal tuberculosis. The patient was commenced on a 24 week course of anti-tuberculous treatment which was interrupted because of a mild course of hospital-acquired coronavirus infection. 3 months after initial treatment for tuberculosis, his sputum cultures became negative. Flexible laryngoscopy was performed at our department 4 months after commencement of treatment, demonstrating complete regression of the lesion and symmetrical laryngeal mobility, hence the patient was successfully decannulated and discharged to be followed up to his community hospital. In the time of COVID-19 pandemic, we should never underestimate other severe infectious diseases.

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