RESUMEN
We observed multisystem inflammatory syndrome in 2 older adults in the United States who had received mRNA coronavirus disease vaccine soon after natural infection. We identified 5 similar cases from the Vaccine Adverse Events Reporting System. The timing of vaccination soon after natural infection might have an adverse effect on the occurrence of vaccine-related systemic inflammatory disorders.
Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Anciano , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , SARS-CoV-2 , Estados Unidos , Vacunación/efectos adversosRESUMEN
Better and more diverse biomarkers for the development of simple point-of-care tests for active tuberculosis (TB), a clinically heterogeneous disease, are urgently needed. We generated a proteomic Mycobacterium tuberculosis (Mtb) High-Density Nucleic Acid Programmable Protein Array (HD-NAPPA) that used a novel multiplexed strategy for expedited high-throughput screening for antibody responses to the Mtb proteome. We screened sera from HIV uninfected and coinfected TB patients and controls (n = 120) from the US and South Africa (SA) using the multiplex HD-NAPPA for discovery, followed by deconvolution and validation through single protein HD-NAPPA with biologically independent samples (n = 124). We verified the top proteins with enzyme-linked immunosorbent assays (ELISA) using the original screening and validation samples (n = 244) and heretofore untested samples (n = 41). We identified 8 proteins with TB biomarker value; four (Rv0054, Rv0831c, Rv2031c and Rv0222) of these were previously identified in serology studies, and four (Rv0948c, Rv2853, Rv3405c, Rv3544c) were not known to elicit antibody responses. Using ELISA data, we created classifiers that could discriminate patients' TB status according to geography (US or SA) and HIV (HIV- or HIV+) status. With ROC curve analysis under cross validation, the classifiers performed with an AUC for US/HIV- at 0.807; US/HIV+ at 0.782; SA/HIV- at 0.868; and SA/HIV+ at 0.723. With this study we demonstrate a new platform for biomarker/antibody screening and delineate its utility to identify previously unknown immunoreactive proteins.
Asunto(s)
Proteínas Bacterianas/inmunología , Infecciones por VIH/sangre , Mycobacterium tuberculosis/metabolismo , Análisis por Matrices de Proteínas/métodos , Proteómica/métodos , Determinación de Anticuerpos Séricos Bactericidas/métodos , Tuberculosis/inmunología , Adulto , Anciano , Biomarcadores/sangre , Coinfección , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Curva ROC , Sudáfrica , Estados Unidos , Adulto JovenRESUMEN
Severe mpox has been observed in people with advanced human immunodeficiency virus (HIV). We describe clinical outcomes of 13 patients with advanced HIV (CD4 <200â cells/µL), severe mpox, and multiorgan involvement. Despite extended tecovirimat courses and additional agents, including vaccinia immune globulin, cidofovir, and brincidofovir, this group experienced prolonged hospitalizations and high mortality.
RESUMEN
Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis (TB) are 2 ends of a spectrum of states ranging from asymptomatic infection to overt disease. While progressing from LTBI to TB, patients often undergo asymptomatic states with detectable manifestations indicative of disease. Such asymptomatic disease states frequently remain undiagnosed, and their manifestations and duration are mostly dependent on host immune response. Various terms referring to such states are used in the literature, often interchangeably and without explicit definitions. Defining these intermediate states in concrete terms is important for pragmatic reasons, as they might impact upon the diagnostic performance of TB biomarkers and could also present targets for therapeutic interventions. We here propose definitions for 2 commonly used terms, "incipient" and "subclinical" TB, to describe asymptomatic disease states occurring at opposite ends of the host response spectrum. We propose using the term "incipient TB" when referring to early, contained disease in asymptomatic, relatively immunocompetent persons. In contrast, we propose using the term "subclinical TB" to refer to disease in asymptomatic, immunocompromised individuals in whom it is largely associated with loss of effective containment. The rationale for this article is to facilitate the discussion of such early disease states, especially in relation to their impact on TB biomarker discovery and assessment of new diagnostics, and with regard to treatment decisions and ultimately outcome.
Asunto(s)
Tuberculosis Latente/inmunología , Mycobacterium tuberculosis/inmunología , Técnicas Bacteriológicas , Biomarcadores/análisis , Progresión de la Enfermedad , Interacciones Huésped-Patógeno , Humanos , Huésped Inmunocomprometido/inmunología , Tuberculosis Latente/clasificación , Tuberculosis Latente/diagnósticoRESUMEN
The ability to utilize leftover samples containing anticoagulants or Ficoll would provide substantial opportunities for future antibody and biomarker studies. Some anticoagulants might influence antibody reactivity against pathogens, but comprehensive studies investigating effects in the context of TB are lacking. We enrolled 24 individuals with and without history of M. tuberculosis and/or HIV-infection and investigated TB antibody reactivities, function, and other host protein biomarkers in simultaneously obtained serum and plasma from serum separation, EDTA, heparin, acid citrate dextrose (ACD), or mononuclear cell preparation (CPT™) tubes which contain heparin and Ficoll. Antibody isotype reactivities to two mycobacterial antigens, as well as phagocytosis of M. tuberculosis, correlated strongly and significantly between serum and plasma, irrespective of type of anticoagulant or Ficoll present (r ≥ 0.85, p < 0.0001). However, the presence of ACD resulted in slightly lower values than those obtained with serum in both indirect (antibody reactivities to mycobacterial antigens) and Sandwich ELISAs (soluble CD14 measurements). Our data demonstrate that leftover plasma, regardless of containing anticoagulants or Ficoll, can be used in TB antibody or other host protein biomarker studies but suggest the value of a correction factor when using ACD plasma interchangeably with serum in antibody binding studies.
Asunto(s)
Anticuerpos Antibacterianos/efectos de los fármacos , Anticoagulantes/farmacología , Ficoll/farmacología , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Especificidad de Anticuerpos/efectos de los fármacos , Antígenos Bacterianos/inmunología , Sitios de Unión de Anticuerpos , Recolección de Muestras de Sangre , Ácido Cítrico/farmacología , Coinfección , Ácido Edético/farmacología , Femenino , Glucosa/análogos & derivados , Glucosa/farmacología , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Heparina/farmacología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/microbiología , Masculino , Persona de Mediana Edad , Fagocitosis/efectos de los fármacos , Células THP-1 , Tuberculosis/sangre , Tuberculosis/microbiologíaRESUMEN
A better understanding of all immune components involved in protecting against Mycobacterium tuberculosis infection is urgently needed to inform strategies for novel immunotherapy and tuberculosis (TB) vaccine development. Although cell-mediated immunity is critical, increasing evidence supports that antibodies also have a protective role against TB. Yet knowledge of protective antigens is limited. Analyzing sera from 97 US immigrants at various stages of M. tuberculosis infection, we showed protective in vitro and in vivo efficacy of polyclonal IgG against the M. tuberculosis capsular polysaccharide arabinomannan (AM). Using recently developed glycan arrays, we established that anti-AM IgG induced in natural infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide motifs within AM and its functions in bacillus Calmette-Guérin vaccination and/or in controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We showed that anti-AM IgG from asymptomatic but not from diseased individuals was protective and provided data suggesting a potential role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Vacuna BCG/inmunología , Inmunoglobulina G/inmunología , Mananos/inmunología , Mycobacterium tuberculosis/inmunología , Oligosacáridos/inmunología , Tuberculosis/inmunología , Animales , Femenino , Humanos , Masculino , Ratones , Células THP-1RESUMEN
Rifamycin-resistant Mycobacterium tuberculosis infection (i.e., by a strain of M. tuberculosis that is only resistant to rifamycins) occurs disproportionately among patients infected with the human immunodeficiency virus (HIV) who have a low CD4 cell count. We observed 3 genetically confirmed cases of relapse with rifamycin-resistant M. tuberculosis infection following concurrent treatment with rifabutin (dosage, 150 mg every other day) and a ritonavir-boosted HIV protease inhibitor during a prior episode of drug-susceptible tuberculosis. Higher doses of rifabutin and a ritonavir-boosted HIV protease inhibitor as treatment for tuberculosis should be studied further.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Infecciones por VIH/complicaciones , Mycobacterium tuberculosis/efectos de los fármacos , Rifabutina/farmacología , Tuberculosis/microbiología , Adulto , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Recurrencia , Rifabutina/uso terapéutico , Ritonavir/uso terapéutico , Resultado del TratamientoRESUMEN
Sputum smear-negative HIV-associated active tuberculosis (TB) is challenging to diagnose. CD14 is a pattern recognition receptor that is known to mediate monocyte activation. Prior studies have shown increased levels of soluble CD14 (sCD14) as a potential biomarker for TB, but little is known about its value in detecting smear-negative HIV-associated TB. We optimized a sandwich ELISA for the detection of sCD14, and tested sera from 56 smear-negative South African (39 culture-positive and 17 culture-negative) HIV-infected pulmonary TB patients and 24 South African and 43 US (21 positive and 22 negative for tuberculin skin test, respectively) HIV-infected controls. SCD14 concentrations were significantly elevated in smear-negative HIV-associated TB compared with the HIV-infected controls (p < 0.0001), who had similar concentrations, irrespective of the country of origin or the presence or absence of latent M. tuberculosis infection (p = 0.19). The culture-confirmed TB group had a median sCD14 level of 2199 ng/mL (interquartile range 1927-2719 ng/mL), versus 1148 ng/mL (interquartile range 1053-1412 ng/mL) for the South African controls. At a specificity of 96%, sCD14 had a sensitivity of 95% for culture-confirmed smear-negative TB. These data indicate that sCD14 could be a highly accurate biomarker for the detection of HIV-associated TB.
Asunto(s)
Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Fluorobencenos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Biomarcadores/sangre , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Masculino , Factores de Riesgo , Rosuvastatina CálcicaRESUMEN
Immune restoration syndromes (IRS) in AIDS constitute a group of illness characterized by a pathologic inflammatory response in patients with late-stage AIDS who start highly active antiretroviral therapy. Although there is no standardized definition or therapy, IRS have partial immune restoration associated with an increase in their CD-4 cell count and a decrease in their viral load. Patients with IRS show a paradoxical reaction that is, clinical worsening rather than improvement on therapy, associated with a recognized or occult infection. Symptoms include new or worsening fever, lymphadenopathy, pulmonary, visceral, central nervous system, or cutaneous disease which may be severe and occasionally life threatening and must be differentiated from disease progression. In this paper, we review the clinical and associated thoracic imaging findings of IRS associated with specific infections including mycobacterial and fungal infections, cytomegalovirus, Pneumocystis jiroveci pneumonia and also Kaposi sarcoma and sarcoidosis. Recognition of the imaging findings in the appropriate clinical setting presents an opportunity to make a timely diagnosis. With appropriate management, IRS usually does not alter long-term prognosis.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico por imagen , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Terapia Antirretroviral Altamente Activa , Radiografía Torácica , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Recuento de Linfocito CD4 , Humanos , Pronóstico , Síndrome , Tomografía Computarizada por Rayos X , Carga ViralAsunto(s)
Bacteriemia/prevención & control , Catéteres de Permanencia/efectos adversos , Infección Hospitalaria/prevención & control , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Sesgo , Sangre/microbiología , Infección Hospitalaria/diagnóstico , Infecciones por Bacterias Gramnegativas/etiología , Humanos , Unidades de Cuidados IntensivosRESUMEN
Intervention at the earliest possible stage of pulmonary tuberculosis (PTB) reduces morbidity for the individual and transmission for the community. We characterize the clinical and radiographic manifestations of sputum culture-negative (Cx-) PTB in order to facilitate awareness of this under recognized and likely early disease state. In this cross-sectional sub-study, we reviewed the medical records of HIV-uninfected PTB patients enrolled from 2006-2014 within the context of a TB biomarker study in New York City. Cx- PTB was defined as clinical and/or radiographic presentation consistent with PTB, three initial mycobacterial sputum cultures negative, and no evidence of other respiratory disease. Diagnosis was confirmed by clinical and radiographic improvement on antituberculous treatment and/or culture, nucleic acid, or histological confirmation from a specimen other than the initial three sputa. Cx+ PTB was defined as above but with M. tuberculosis growth in at least one of the first three sputum cultures. Demographics, symptoms, and radiographic findings on initial presentation were compared between the two groups. Of 99 subjects diagnosed with PTB, 21 met the criteria of Cx- PTB. Cx- compared to Cx+ subjects presented with a significantly lower frequency of cough (70% vs. 91%, P = 0.02), sputum production (30% vs. 64%, P < 0.01), weight loss (25% vs. 54%, P = 0.02), and frequency of cavitation on chest CT (12% vs. 68%, P < 0.01). Our findings should raise awareness that neither a positive culture nor the hallmark symptoms are invariably associated with early TB disease.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar/diagnóstico por imagen , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Esputo/microbiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
Five of 10 patients who commenced successful highly active antiretroviral therapy (HAART) for infection with human immunodeficiency virus type 1 (HIV-1) concurrent with or soon after a diagnosis of cryptococcal infection experienced clinical events characterized by sterile inflammation. Two patients developed aseptic meningitis with elevated intracranial pressure, 1 developed intrathoracic lyphadenopathy with hypercalcemia, 1 developed cavitary pneumonia at the site of a cryptococcal nodule, and 1 developed a supraclavicular abscess. These events occurred 2-11 months after initiation of HAART. For 3 patients, biopsy demonstrated findings atypical for acquired immunodeficiency syndrome-associated cryptococcosis. Results of fungal cultures were negative for all 5 patients, and cryptococcal antigen levels had declined markedly in 4 patients. The timing and clinical features of and biopsy findings for these cases of cryptococcosis suggest the existence of a paradoxical reaction to Cryptococcus infection that occurs in the context of HIV immune restoration.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Criptococosis/etiología , Cryptococcus/inmunología , Infecciones por VIH/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Criptococosis/inmunología , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men. No association was found with baseline CD4+ cell count or HIV RNA level. The prevalence of HCV coinfection in a diverse HIV clinical trials cohort provides additional information about risk behaviors and demographic factors that can be used in the analysis of clinical and virologic outcomes.
Asunto(s)
Infecciones por VIH/complicaciones , VIH , Hepacivirus , Hepatitis C/complicaciones , Adulto , Recuento de Linfocito CD4 , Ensayos Clínicos como Asunto , Estudios de Cohortes , Femenino , Infecciones por VIH/inmunología , Hepatitis C/epidemiología , Humanos , Masculino , Análisis Multivariante , PrevalenciaAsunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , VIH/genética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adenina/análogos & derivados , Adenina/uso terapéutico , Densidad Ósea/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Emtricitabina , Humanos , Lamivudine/uso terapéutico , Mutación , Organofosfonatos/uso terapéutico , Tenofovir , Zidovudina/uso terapéuticoRESUMEN
Serology data are limited for patients with sputum smear-negative HIV-associated active tuberculosis (TB). We evaluated the serum antibody responses against the mycobacterial proteins MPT51, MS, and echA1 and the 38-kDa protein via enzyme-linked immunosorbent assay (ELISA) in South African (S.A.) HIV-positive (HIV(+)) smear-negative TB patients (n = 56), U.S. HIV(+) controls with a positive tuberculin skin test (TST(+); n = 21), and S.A. HIV-negative (HIV(-)) (n = 18) and HIV(+) (n = 24) controls. TB patients had positive antibody reactivity against MPT51 (73%), echA1 (59%), MS (36%), and the 38-kDa protein (11%). Little reactivity against MPT51 and echA1 was observed in control groups at low risk for TB, i.e., S.A. HIV(-) (0% and 6%, respectively), and at moderate risk for TB development, i.e., U.S. HIV(+) TST(+) controls (14% and 10%, respectively). By contrast, more reactivity was detected in the S.A. HIV(+) control group at higher risk for TB (25% and 45%, respectively). Our data hold promise that antibody detection against MPT51 and echA1 might have adjunctive value in the detection of HIV(+) smear-negative TB and might reflect increasing Mycobacterium tuberculosis infection activity in asymptomatic HIV(+) individuals.