RESUMEN
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.
Asunto(s)
Ensayos de Liberación de Interferón gamma , Mycobacterium tuberculosis , Valor Predictivo de las Pruebas , Prueba de Tuberculina , Tuberculosis , Humanos , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Tuberculosis/microbiología , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Factores de Riesgo , Interacciones Huésped-Patógeno , Antígenos Bacterianos/inmunología , Medición de Riesgo , Progresión de la Enfermedad , Pronóstico , Biomarcadores/sangre , Factores de TiempoRESUMEN
One of the primary public health functions of a tuberculosis (TB) program is to arrest the spread of infection. Traditionally, TB programs have relied on epidemiological information, gathered through contact tracing, to infer that transmission has occurred between people. The ability of drawing such inferences is extensively context dependent. Where epidemiological information has been strong, such as 2 cases of TB occurring sequentially within a single household, confidence in such inferences is high; conversely, public health authorities have been less certain about the significance of TB cases merely occurring in the same wider social group or geographic area. Many current laboratory tests for TB used globally may be sufficient to confirm a diagnosis and guide appropriate therapy but still be insufficiently precise for distinguishing two strains reliably. In short, drawing inferences regarding a chain of transmissions has always been as much art as science.
Asunto(s)
Tuberculosis , Secuenciación Completa del Genoma , Humanos , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/transmisión , Tuberculosis/genética , Secuenciación Completa del Genoma/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Trazado de Contacto/métodos , Salud Pública/métodos , NarraciónRESUMEN
The changing phenotype of coronarvirus disease 2019 (COVID-19) may quickly render guideline-recommended interventions obsolete. We developed a 40-question clinician survey in consultation with the Australasian COVID-19 Trial site investigators. The survey was designed to assess clinician perceptions of the current treatment strategies and future research priorities in the management of non-critically ill patients admitted to hospital with SARS-CoV-2 infection. There were 84 complete responses from predominantly Australian and New Zealand clinicians. The perceived prevalence of patients with incidental COVID-19, nosocomial infection, underlying illness exacerbated by COVID-19, and/or immunocompromised status suggests new populations to target. The results highlighted clinician interest in antiviral therapies for future research in both immunocompetent and immunocompromised cohorts. These survey results underscore the need for ongoing surveillance of COVID-19 disease phenotypes and clinician and patient priorities for future research.
Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Australia/epidemiología , Hospitales , InvestigaciónRESUMEN
We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB).
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Mycobacterium tuberculosis/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance. METHODS: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context. RESULTS: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs. CONCLUSION: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Isoniazida/farmacología , Isoniazida/uso terapéutico , Victoria/epidemiología , Filogenia , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Secuenciación Completa del Genoma , Mutación , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
BACKGROUND: The prevalence of tuberculosis infection is critical to the design of tuberculosis prevention strategies, yet is unknown in Canada. We estimated the prevalence of tuberculosis infection among Canadian residents born abroad. METHODS: We estimated the prevalence of tuberculosis infection by age and year of migration to Canada for people from each of 168 countries by constructing country-specific and calendar year-specific trends for annual risk of infection using a previously developed model. We combined country-specific prevalence estimates with Canadian Census data from 2001, 2006, 2011, 2016 and 2021 to estimate the overall prevalence of tuberculosis infection among foreign-born Canadian residents. RESULTS: The estimated overall prevalence of tuberculosis infection among foreign-born people in Canada was 25% (95% uncertainty interval [UI] 20%-35%) for census year 2001, 24% (95% UI 20%-33%) for 2006, 23% (95% UI 19%-30%) for 2011, 22% (95% UI 19%-28%) for 2016 and 22% (95% UI 19%-27%) for 2021. The prevalence increased with age at migration and incidence of tuberculosis in the country of origin. In 2021, the estimated prevalence of infection among foreign-born residents was lowest in Quebec (19%, 95% UI 16%-24%) and highest in Alberta (24%, 95% UI 21%-28%) and British Columbia (24%, 95% UI 20%-30%). Among all foreign-born Canadian residents with tuberculosis infection in 2021, we estimated that only 1 in 488 (95% UI 185-1039) had become infected within the 2 preceding years. INTERPRETATION: About 1 in 4 foreign-born Canadian residents has tuberculosis infection, but very few were infected within the 2 preceding years (the highest risk period for progression to tuberculosis disease). These data may inform future tuberculosis infection screening policies.
Asunto(s)
Emigrantes e Inmigrantes , Tuberculosis Latente , Tuberculosis , Humanos , Incidencia , Tuberculosis Latente/epidemiología , Prevalencia , Tuberculosis/epidemiología , Canadá/epidemiologíaRESUMEN
The Australian Partnership for Preparedness Research on InfectiouS disease Emergencies (APPRISE) has developed a virtual biobank to support infectious disease research in Australia. The virtual biobank (https://apprise.biogrid.org.au) integrates access to existing distributed infectious disease biospecimen collections comprising multiple specimen types, including plasma, serum, and peripheral blood mononuclear cells. Through the development of a common data model, multiple collections can be searched simultaneously via a secure web portal. The portal enhances the visibility and searchability of existing collections within their current governance and custodianship arrangements. The portal is easily scalable for integration of additional collections.
Asunto(s)
Bancos de Muestras Biológicas , Enfermedades Transmisibles , Humanos , Australia/epidemiología , Leucocitos Mononucleares , Manejo de EspecímenesRESUMEN
BACKGROUND: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. METHODS: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. RESULTS: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). CONCLUSIONS: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.
Asunto(s)
COVID-19 , Coinfección , Infecciones por VIH , Tuberculosis Miliar , Humanos , Masculino , COVID-19/complicaciones , Infecciones por VIH/complicaciones , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Background: The management of infective endocarditis (IE) is complex owing to a high burden of morbidity and mortality. Recent guidelines recommend dedicated multidisciplinary teams (MDTs) for the management of IE. The aim of this systematic review and meta-analysis was to evaluate and summarize the effect of MDT management on patient outcomes. Methods: A systematic review was performed and, where feasible, results were meta-analyzed; otherwise, results were summarized narratively. Data extraction and quality assessment were performed in duplicate. Restricted maximum likelihood random effects models were used to calculate unadjusted risk ratios and 95% CIs. Results: Screening of 2343 studies based on title and abstract yielded 60 full-text reviews; 18 studies were summarized narratively, of which 15 were included in a meta-analysis of short-term mortality. Meta-analysis resulted in a risk ratio of 0.61 (95% CI, .47-.78; I2 = 62%) for mortality in favor of a dedicated MDT as compared with usual care. Length of stay was variable, with 55% (10/18) of studies reporting an increased length of stay. Most studies (16/18, 88.9%) reported a decreased time to surgery and an increased rate of surgery (13/18, 73%). No studies reported on patient-reported outcomes. Conclusions: This is the first systematic review and meta-analysis to assess the impact of MDT management on IE. The sum of evidence demonstrated a significant association between MDTs and improved short-term mortality. Further research is needed to evaluate benefits of virtual MDT care, cost-effectiveness, and the impact on patient-reported outcomes and long-term mortality.
RESUMEN
BACKGROUND: Non-adherence to treatment is a frequently observed phenomenon amongst those on long-term treatment for chronic illnesses. This qualitative study draws upon the tenets of 'practice theory' to reveal what shapes patients' ability to adhere to the demanding treatment for drug-resistant tuberculosis (DR-TB) at three treatment sites in Khyber-Pakhtunkhwa (KP) province of Pakistan. METHODS: This qualitative study involved observation of service provision over a period of nine months of stay at, and embedment within the three treatment sites and in-depth interviews with 13 service providers and 22 patients who became non-adherent to their treatment. RESULTS: Consistent with the extensive research based on the barriers and facilitator approach, both patients, and providers in our study also talked of patients' doubts about diagnosis and treatment efficacy, side-effects of drugs, economic constraints, unreliable disbursements of monetary incentive, attitude of providers and co-morbidities as reasons for non-adherence to treatment. Applying a practice theory perspective yielded more contextualised insights; inadequate help with patients' physical complaints, unempathetic responses to their queries, and failure to provide essential information, created conditions which hindered the establishment and maintenance of the 'practice' of adhering to treatment. These supply-side gaps created confusion, bred resentment, and exacerbated pre-existing distrust of public health services among patients, and ultimately drove them to disengage with the TB services and stop their treatment. CONCLUSION: We argue that the lack of supply-side 'responsiveness' to patient needs beyond the provision of a few material inputs is what is lacking in the existing DR-TB program in Pakistan. We conclude that unless Pakistan's TB program explicitly engages with these supply side, system level gaps, patients will continue to struggle to adhere to their treatments and the TB program will continue to lose patients. Conceptually, we make a case for reimagining the act of adherence (or not) to long-term treatment as a 'Practice.'
Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Pakistán , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Resultado del Tratamiento , Enfermedad CrónicaRESUMEN
BACKGROUND: People who are incarcerated are at high risk of developing tuberculosis. We aimed to estimate the annual global, regional, and national incidence of tuberculosis among incarcerated populations from 2000 to 2019. METHODS: We collected and aggregated data for tuberculosis incidence and prevalence estimates among incarcerated individuals in published and unpublished literature, annual tuberculosis notifications among incarcerated individuals at the country level, and the annual number of incarcerated individuals at the country level. We developed a joint hierarchical Bayesian meta-regression framework to simultaneously model tuberculosis incidence, notifications, and prevalence from 2000 to 2019. Using this model, we estimated trends in absolute tuberculosis incidence and notifications, the incidence and notification rates, and the case detection ratio by year, country, region, and globally. FINDINGS: In 2019, we estimated a total of 125â105 (95% credible interval [CrI] 93â736-165â318) incident tuberculosis cases among incarcerated individuals globally. The estimated incidence rate per 100â000 person-years overall was 1148 (95% CrI 860-1517) but varied greatly by WHO region, from 793 (95% CrI 430-1342) in the Eastern Mediterranean region to 2242 (1515-3216) in the African region. Global incidence per 100â000 person-years between 2000 and 2012 among incarcerated individuals decreased from 1884 (95% CrI 1394-2616) to 1205 (910-1615); however, from 2013 onwards, tuberculosis incidence per 100â000 person-years was stable, from 1183 (95% CrI 876-1596) in 2013 to 1148 (860-1517) in 2019. In 2019, the global case detection ratio was estimated to be 53% (95% CrI 42-64), the lowest over the study period. INTERPRETATION: Our estimates suggest a high tuberculosis incidence rate among incarcerated individuals globally with large gaps in tuberculosis case detection. Tuberculosis in incarcerated populations must be addressed with interventions specifically tailored to improve diagnoses and prevent transmission as a part of the broader global tuberculosis control effort. FUNDING: National Institutes of Health.
Asunto(s)
Prisioneros , Tuberculosis , Estados Unidos , Humanos , Teorema de Bayes , Incidencia , Tuberculosis/epidemiologíaRESUMEN
Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.
Asunto(s)
Endocarditis Bacteriana , Endocarditis , Guías de Práctica Clínica como Asunto , Adulto , Humanos , Consenso , Endocarditis/diagnóstico , Endocarditis/terapia , Endocarditis Bacteriana/prevención & control , Estudios ProspectivosRESUMEN
Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.
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COVID-19 , Embarazo , Femenino , Humanos , SARS-CoV-2 , Células Asesinas Naturales , Linfocitos T CD8-positivos , AnticuerposRESUMEN
Tuberculosis (TB) elimination and pre-elimination, with thresholds of 1 and 10 incident cases per million population, respectively, were considered achievable for low TB incidence countries in the 1990s, when they were conceived. However, it has since become clear that, even in low TB incidence settings with effective programmes and sufficient resources, achieving pre-elimination in the next decade will require a dramatic acceleration of efforts. In this review, we describe the history of the TB elimination concept and existing country experiences, as well as the interventions available to accelerate the progress towards this threshold. We then propose a framework for near-term progress towards the more aspirational goal of TB pre-elimination. This framework consists of five stages (high incidence, moderate incidence, low incidence, nearing pre-elimination and pre-elimination) that are benchmarked to specific levels of TB incidence in each country. Using this framework, countries can set 5-year targets of achieving certain reductions in TB incidence and/or reaching the next stage, through the use of strategies tailored to both local epidemiology and available organisation and infrastructure. TB elimination remains as an aspirational goal in all stages, but certain activities can be prioritised in the short term to make more rapid progress, ensure local-level buy-in and increase accountability. As TB pre-elimination is approached, certain ethical and social concerns are likely to rise in importance; these concerns are also discussed. Our aim in setting this framework is to guide clinicians, public health experts and decision makers in taking actionable next steps in the trajectory towards TB pre-elimination and elimination.
Asunto(s)
Antituberculosos , Tuberculosis , Humanos , Antituberculosos/uso terapéutico , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Tuberculosis/tratamiento farmacológico , Incidencia , Salud PúblicaRESUMEN
BACKGROUND: Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes. METHODS: Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094). CONCLUSION: Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB.
Asunto(s)
Tuberculosis Extrapulmonar , Tuberculosis , Humanos , Victoria/epidemiología , Estudios Retrospectivos , Incidencia , Salud Pública , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/diagnósticoRESUMEN
OBJECTIVES: Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. METHODS: TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). RESULTS: Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. CONCLUSIONS: A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.
Asunto(s)
COVID-19 , Tuberculosis Miliar , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de COVID-19 , Europa (Continente)/epidemiología , América del Norte/epidemiología , Pandemias , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiologíaRESUMEN
BACKGROUND: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with coronavirus disease 2019 (Covid-19). Participants were randomly assigned to usual care or usual care plus nafamostat. The primary end point was death (any cause) or receipt of new invasive or noninvasive ventilation or vasopressor support within 28 days after randomization. Analysis was with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to falling numbers of eligible patients. RESULTS: We screened 647 patients in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal) and enrolled 160 participants from May 2021 to August 2022. In the intention-to-treat population, the primary end point occurred in 8 (11%) of 73 patients with usual care and 4 (5%) of 82 with nafamostat. The median adjusted odds ratio for the primary end point for nafamostat was 0.40 (95% credible interval, 0.12 to 1.34) with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%. For usual care compared with nafamostat, hyperkalemia occurred in 1 (1%) of 67 and 7 (9%) of 78 participants, respectively, and clinically relevant bleeding occurred in 1 (1%) of 73 and 7 (8%) of 82 participants. CONCLUSIONS: Among hospitalized patients with Covid-19, there was a 93% posterior probability that nafamostat reduced the odds of death or organ support. Prespecified stopping criteria were not met, precluding definitive conclusions. Hyperkalemia and bleeding were more common with nafamostat. (Funded by ASCOT and others; ClinicalTrials.gov number, NCT04483960.)