RESUMEN
Development of a safe and effective human immunodeficiency virus (HIV) vaccine is a persistent challenge despite decades of research. Previous strategies utilizing protein subunit and viral vector vaccines were safe but not protective. Current strategies seek to induce broadly neutralizing antibodies, with multiple early phase trials in progress seeking to achieve this through sequential vaccination, mRNA, or updated viral-vectored vaccines. A safe and effective vaccine is critical to ending the HIV epidemic.
Asunto(s)
Vacunas contra el SIDA , Infecciones por VIH , Humanos , Vacunas contra el SIDA/inmunología , Vacunas contra el SIDA/administración & dosificación , Infecciones por VIH/prevención & control , Anticuerpos Neutralizantes/inmunología , VIH-1/inmunología , Anticuerpos Anti-VIH/inmunología , Desarrollo de VacunasRESUMEN
Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation with cell-based pseudovirus neutralization activity (PNA) and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta and omicron variant resistance to neutralization in samples with paired vaccine strain and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. Importantly, this completely automated assay can be performed in 4 h to measure neutralizing antibody titers for 16 samples over 8 serial dilutions or, 128 samples at a single dilution with replicates. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.
RESUMEN
Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2/genética , COVID-19/prevención & control , Anticuerpos ampliamente neutralizantesRESUMEN
Importance: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders. Objective: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection. Design, Setting, and Participants: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group within each vaccine trial. Data were analyzed from April 2022 to February 2023. Exposures: Comorbid conditions, demographic factors, and SARS-CoV-2 exposure risk at the time of enrollment. Main Outcomes and Measures: Coprimary outcomes were COVID-19 and severe COVID-19. Multivariate Cox proportional regression models estimated adjusted hazard ratios (aHRs) and 95% CIs for baseline covariates, accounting for trial, region, and calendar time. Secondary outcomes included severe COVID-19 among people with COVID-19, subclinical SARS-CoV-2 infection, and SARS-CoV-2 infection. Results: A total of 57â¯692 participants (median [range] age, 51 [18-95] years; 11â¯720 participants [20.3%] aged ≥65 years; 31â¯058 participants [53.8%] assigned male at birth) were included. The analysis population included 3270 American Indian or Alaska Native participants (5.7%), 7849 Black or African American participants (13.6%), 17â¯678 Hispanic or Latino participants (30.6%), and 40â¯745 White participants (70.6%). Annualized incidence was 13.9% (95% CI, 13.3%-14.4%) for COVID-19 and 2.0% (95% CI, 1.8%-2.2%) for severe COVID-19. Factors associated with increased rates of COVID-19 included workplace exposure (high vs low: aHR, 1.35 [95% CI, 1.16-1.58]; medium vs low: aHR, 1.41 [95% CI, 1.21-1.65]; P < .001) and living condition risk (very high vs low risk: aHR, 1.41 [95% CI, 1.21-1.66]; medium vs low risk: aHR, 1.19 [95% CI, 1.08-1.32]; P < .001). Factors associated with decreased rates of COVID-19 included previous SARS-CoV-2 infection (aHR, 0.13 [95% CI, 0.09-0.19]; P < .001), age 65 years or older (aHR vs age <65 years, 0.57 [95% CI, 0.50-0.64]; P < .001) and Black or African American race (aHR vs White race, 0.78 [95% CI, 0.67-0.91]; P = .002). Factors associated with increased rates of severe COVID-19 included race (American Indian or Alaska Native vs White: aHR, 2.61 [95% CI, 1.85-3.69]; multiracial vs White: aHR, 2.19 [95% CI, 1.50-3.20]; P < .001), diabetes (aHR, 1.54 [95% CI, 1.14-2.08]; P = .005) and at least 2 comorbidities (aHR vs none, 1.39 [95% CI, 1.09-1.76]; P = .008). In analyses restricted to participants who contracted COVID-19, increased severe COVID-19 rates were associated with age 65 years or older (aHR vs <65 years, 1.75 [95% CI, 1.32-2.31]; P < .001), race (American Indian or Alaska Native vs White: aHR, 1.98 [95% CI, 1.38-2.83]; Black or African American vs White: aHR, 1.49 [95% CI, 1.03-2.14]; multiracial: aHR, 1.81 [95% CI, 1.21-2.69]; overall P = .001), body mass index (aHR per 1-unit increase, 1.03 [95% CI, 1.01-1.04]; P = .001), and diabetes (aHR, 1.85 [95% CI, 1.37-2.49]; P < .001). Previous SARS-CoV-2 infection was associated with decreased severe COVID-19 rates (aHR, 0.04 [95% CI, 0.01-0.14]; P < .001). Conclusions and Relevance: In this secondary cross-protocol analysis of 4 randomized clinical trials, exposure and demographic factors had the strongest associations with outcomes; results could inform mitigation strategies for SARS-CoV-2 and viruses with comparable epidemiological characteristics.
Asunto(s)
COVID-19 , Adulto , Humanos , Masculino , Persona de Mediana Edad , COVID-19/epidemiología , Vacunas contra la COVID-19 , Demografía , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , Adolescente , Adulto Joven , Anciano , Anciano de 80 o más AñosRESUMEN
Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.
RESUMEN
INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of global morbidity and mortality, affecting nearly a quarter of the human population and accounting for over 10 million deaths each year. Over the past several decades, TB incidence and mortality have gradually declined, but 2021 marked a threatening reversal of this trend highlighting the importance of accurate diagnosis and effective treatment of all forms of TB. AREAS COVERED: This review summarizes advances in TB diagnostics, addresses the treatment of people with TB infection and TB disease including recent evidence for treatment regimens for drug-susceptible and drug-resistant TB, and draws attention to special considerations in children and during pregnancy. EXPERT OPINION: Improvements in diagnosis and management of TB have expanded the available options for TB control. Molecular testing has enhanced the detection of TB disease, but better diagnostics are still needed, particularly for certain populations such as children. Novel treatment regimens have shortened treatment and improved outcomes for people with TB. However, important questions remain regarding the optimal management of TB. Work must continue to ensure the potential of the latest developments is realized for all people affected by TB.
Asunto(s)
Tuberculosis Latente , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Niño , Humanos , Antituberculosos/uso terapéutico , Tuberculosis/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Latente/tratamiento farmacológico , Antígenos BacterianosRESUMEN
Background: Hybrid immunity is associated with more durable protection against coronavirus disease 2019 (COVID-19). We describe the antibody responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated and unvaccinated individuals. Methods: The 55 vaccine arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens (ancestral and variants of concern [VOCs]) were assessed on disease day 1 (DD1) and 28â days later (DD29). Results: The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post-first dose. For vaccine group cases, there was a 1.88-fold rise in ancestral antispike bAbs 1 month post-disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 antispike and antinucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group. Conclusions: Following COVID-19, vaccinated participants had higher levels and greater breadth of antispike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.
RESUMEN
We describe severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG seroprevalence and antigenemia among patients at a medical center in January-March 2021 using residual clinical blood samples. The overall seroprevalences were 17% by infection and 16% by vaccination. Spent or residual samples are a feasible alternative for rapidly estimating seroprevalence or monitoring trends in infection and vaccination.
RESUMEN
Cryptococcoid Sweet syndrome is a rare histologic variant of the neutrophilic dermatosis presenting clinically with skin lesions typical of classical Sweet syndrome but with yeast-like structures suggestive of Cryptococcus on histopathology. Histochemical stains for fungus and cultures are negative whereas staining for myeloperoxidase is positive. We present 2 cases of cryptococcoid Sweet syndrome with atypical skin manifestations, including hemorrhagic bullae and plaques, and provide a brief review of the literature. Clinicians should be aware that this variant of Sweet syndrome can present with uncommon clinical findings and has histopathologic findings suggestive of Cryptococcus species.
RESUMEN
Although linezolid is effective for multidrug-resistant TB (MDR-TB) tuberculosis treatment, it is associated with cytopenias after 4 weeks of administration. Data on toxicities with long-term use of linezolid and drug pharmacodynamics in MDR-TB treatment are limited, and concerns about toxicity present barriers to wider implementation. This was a secondary analysis of a prospective cohort study of patients treated for MDR-TB in the country of Georgia from 2015 to 2017. Intensive blood sampling 4 to 6 weeks after treatment initiation with linezolid 600 mg daily was performed for pharmacokinetic (PK) analysis, including linezolid trough concentration (Cmin) and area under the curve from 0 to 24 hours (AUC0-24). Linezolid exposure was defined using literature-reported thresholds. Cytopenias were defined using an NIH adverse event (AE) scale. Logistic regression was used to evaluate the relationship between linezolid exposure and cytopenias. Among 76 patients receiving linezolid in their baseline treatment regimen and who had PK data available, cytopenia AEs occurred in 30 (39.5%) for an incidence rate of 46 per 100 person-years. The median duration of linezolid therapy was 526 days. No patients required dose reduction or interruption due to cytopenias. Median linezolid Cmin was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC0-24 was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters (Cmin > 2 mg/L and AUC0-24 > 160 mg·h/L). Cytopenias occurred frequently with long-term use of linezolid 600 mg/day and were associated with PK parameters but did not result in the need for treatment interruption in the management of a cohort of patients with MDR-TB.
Asunto(s)
Antituberculosos , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos/efectos adversos , Humanos , Incidencia , Linezolid/efectos adversos , Estudios Prospectivos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID 50 ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. Clinicaltrialsgov: NCT05289037.
RESUMEN
Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential for diagnosis, treatment, and infection control. Polymerase chain reaction (PCR) fails to distinguish acute from resolved infections, as RNA is frequently detected after infectiousness. We hypothesized that nucleocapsid in blood marks acute infection with the potential to enhance isolation and treatment strategies. In a retrospective serosurvey of inpatient and outpatient encounters, we categorized samples along an infection timeline using timing of SARS-CoV-2 testing and symptomatology. Among 1860 specimens from 1607 patients, the highest levels and frequency of antigenemia were observed in samples from acute SARS-CoV-2 infection. Antigenemia was higher in seronegative individuals and in those with severe disease. In our analysis, antigenemia exhibited 85.8% sensitivity and 98.6% specificity as a biomarker for acute coronavirus disease 2019 (COVID-19). Thus, antigenemia sensitively and specifically marks acute SARS-CoV-2 infection. Further study is warranted to determine whether antigenemia may aid individualized assessment of active COVID-19.
Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Prueba de COVID-19 , Estudios Retrospectivos , Sensibilidad y Especificidad , Nucleocápside , BiomarcadoresRESUMEN
We assessed the prevalence of antibiotic prescriptions among ambulatory patients tested for coronavirus disease 2019 (COVID-19) in a large public US healthcare system and found a low overall rate of antibiotic prescriptions (6.7%). Only 3.8% of positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) tests were associated with an antibiotic prescription within 7 days.
RESUMEN
Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for a third dose of vaccine. We evaluated early safety and immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, and Delta variants that were similar or greater than peak responses after the second dose. Spike-specific CD4+ and CD8+ T cells increased to similar levels as after the second dose. A third mRNA vaccination was well tolerated and generated robust humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1).
RESUMEN
BACKGROUND: Estimates of the prevalence of SARS-CoV-2 antibodies and factors associated with infection among healthcare personnel (HCP) vary widely. We conducted a serosurvey of HCP at a large public healthcare system in the Atlanta area. MATERIALS AND METHODS: All employees of Grady Health System were invited to participate in mid-2020; a volunteer sample of those completing testing was included. Asymptomatic HCP were offered testing for IgG antibody and for SARS-CoV-2 RNA using polymerase chain reaction (PCR). Symptomatic HCP were offered PCR testing. Antibody index values for IgG and cycle threshold values for PCR were evaluated for those with a positive result. An online survey was distributed at the time of testing. RESULTS: 624 of 1677 distributed surveys (37.2%) were completed by 608 unique HCP. The majority were female (76.4%) and provided clinical care (70.9%). The most common occupations were clinician (24.8%) and nurse (23.5%). 37 of 608 (6.1%) HCP had detectable IgG. Exposure to a confirmed case of COVID-19 outside of the hospital was associated with detectable IgG (12.8% vs 4.4%, p = 0.02), but exposure to a patient with COVID-19 was not. CONCLUSIONS: Among HCP in a large healthcare system, 6.1% had detectable SARS-CoV-2 IgG. Seropositivity was associated with exposures outside of the healthcare setting.
Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/diagnóstico , COVID-19/epidemiología , Atención a la Salud , Femenino , Personal de Salud , Humanos , Inmunoglobulina G , Masculino , ARN Viral , Estudios SeroepidemiológicosRESUMEN
While the development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines was rapid, time to development and implementation challenges remain that may impact the response to future pandemics. Trained immunity via bacille Calmette-Guerin (BCG) vaccination (an antigen agnostic strategy) offers a potential intervention against future novel pathogens via an existing, safe, and widely distributed vaccine to protect vulnerable populations and preserve health system capacity while targeted vaccines are developed and implemented.
RESUMEN
Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.
RESUMEN
Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.
RESUMEN
Paroxysmal nocturnal hemoglobinuria is a clonal hematopoietic stem cell disorder resulting in complement-mediated hemolysis. Eculizumab, a monoclonal antibody against complement protein C5, has been shown to reduce both intravascular hemolysis and risk for thrombosis, and thereby improve the quality of life in these patients. While the infection risk from Neisseria meningitidis due to terminal complement blockade can be mitigated with appropriate immunizations and prophylactic antibiotics, these patients remain vulnerable to infections from Neisseria gonorrhoeae. Physicians and families should be aware of disseminated and severe gonococcal infections in patients receiving complement blockade, especially in this era of emerging cephalosporin and azithromycin resistance.
Asunto(s)
Hemoglobinuria Paroxística , Calidad de Vida , Complemento C5 , Proteínas del Sistema Complemento , Hemoglobinuria Paroxística/tratamiento farmacológico , Hemólisis , HumanosRESUMEN
BACKGROUND: Although rapid molecular diagnostic tests for tuberculosis (TB) have decreased detection time of Mycobacterium tuberculosis and drug resistance, whether their use improves clinical care and outcomes is uncertain. To address these knowledge gaps, we evaluated whether use of the Xpert MTB/RIF assay impacts treatment and clinical outcome metrics among patients treated for sputum smear-negative multidrug-resistant (MDR)-TB. METHODS: We conducted a retrospective cohort study of adult patients initiating treatment for sputum smear-negative MDR-TB at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia from 2011 to 2016. The Xpert MTB/RIF was introduced in Georgia in 2010 and implemented into programmatic use in 2014. Exposure was availability of an Xpert result at time of diagnosis. Time to second-line treatment initiation, sputum culture conversion, and end-of-treatment outcomes were determined. Time to event was compared using a Cox proportional hazards model. RESULTS: Among 151 patients treated for sputum smear-negative MDR-TB (96% culture positive), the Xpert was utilized in the clinical management of 78 (52%) patients and not used in 73 (48%). An adjusted analysis controlling for potential confounders found that patients in the Xpert group had shorter median time to second-line treatment (13 vs 56 days; adjusted hazard ratio [aHR], 10.21; Pâ <â .0001) and culture conversion (61 vs 93 days; aHR, 1.93; Pâ <â .001). There was no difference in treatment outcomes. CONCLUSIONS: Use of the Xpert in the management of sputum smear-negative MDR-TB decreases time to second-line therapy and sputum culture conversion, providing evidence of its clinical impact and supporting its programmatic utility.