scholarly journals Antibody Responses in HIV-Infected Patients With Advanced Immunosuppression and Asymptomatic Cryptococcal Antigenemia

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Admire Hlupeni ◽  
Antonio Nakouzi ◽  
Tao Wang ◽  
Kathryn F Boyd ◽  
Tariro A Makadzange ◽  
...  

Abstract Background There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/µL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg- patients. Methods We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/µL; 125 CrAg- and CrAg+ but cerebrospinal fluid CrAg- by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1–3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results GXM-IgG, -IgM, and -IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg- patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG, -IgG2, and -IgM, this model had an 80.4% probability (95% confidence interval, 0.75–0.86) of predicting CrAg+ status. Conclusions Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 276-276
Author(s):  
Joseph Church

HIV-infected children are at risk for developing disseminated MAC infection. Children older than 5 years and those with CD4+ T-cell counts <100/mm3 (<100 x 106/liter) are at greatest risk.


2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.


2019 ◽  
Vol 37 (07) ◽  
pp. 731-737 ◽  
Author(s):  
Audrey A. Merriam ◽  
Chia-Ling Nhan-Chang ◽  
B. Isabel Huerta-Bogdan ◽  
Ronald Wapner ◽  
Cynthia Gyamfi-Bannerman

Objective Our institution is in an area of New York City with a large population of immigrants from Zika virus endemic areas. With the recent Zika virus outbreak, we sought to examine our center's experience with screening for Zika virus and outcomes among patients who tested positive for the disease during pregnancy. Study Design We performed a chart review of all pregnant patients who tested positive (positive serum or urine polymerase chain reaction [PCR]) or presumed positive (immunoglobulin M [IgM] enzyme-linked immunosorbent assay [ELISA] positive or IgM ELISA equivocal with positive plaque reduction neutralization test) for Zika virus. All tests were performed by the Department of Health (DOH) and followed Centers for Disease Control and Prevention guidelines in effect at the time of specimen collection. Testing of cord blood, placenta, and/or neonatal blood were/was performed by the DOH for New York County. Prenatal ultrasounds for fetal head size and surveillance for calcifications were performed by maternal–fetal medicine specialists. Infant head ultrasound results were included when available. Results Between March 2016 and April 2017, 70 pregnant patients were positive or presumed positive for Zika infection during pregnancy. Of those, 16 women had positive urine or serum PCR and the remaining 54 were presumed positive. Among positive cases, five women tested positive via urine PCR only, nine women tested positive via serum PCR only, and two women had both positive urine and serum PCR. Fifteen of 67 infants (22%) born during the study period were born to mothers with positive urine or serum PCR testing. Sixty-five newborns were clinically normal with normal head measurements. Of the intracranial ultrasound performed, one infant had a grade 1 intraventricular hemorrhage, four had incidental choroid plexus cysts, and one had severe ventriculomegaly that was also noted antenatally. There were 2 positive and 15 equivocal infant serum IgM samples and 1 positive placental PCR from these pregnancies. There were four pregnancy terminations and two cases with fetal anomalies in this population that were split evenly between patients who tested positive and those who tested presumed positive for Zika virus during pregnancy. Conclusion We found no differences in pregnancy or neonatal outcomes between women who tested positive and presumed positive for Zika virus during pregnancy. Testing of infants and placenta tissue after delivery was largely inconclusive. Improvement in testing for Zika virus infection is needed to determine which pregnancies are at risk for congenital anomalies. Further research is still needed to determine which children are at risk for poor neurodevelopmental outcomes related to Zika virus and how to best coordinate care among the immigrant population during a new disease epidemic.


2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Win Le Shwe Sin Ei ◽  
Kyi Pyar Soe ◽  
Adelene Hilbig ◽  
Jillian Murray ◽  
David Heiden

Abstract A retrospective review of diagnosis of cytomegalovirus retinitis (CMVR) before and after introduction of routine immediate eye examination among AIDS patients in Myanmar with an absolute CD4 T-cell count &lt;100 cells/μL demonstrated an increased detection of CMVR from 1.1% (14/1233) to 10.7% (65/608), an improvement of ~10-fold. Diagnosis of CMVR was achieved a mean of 2 days after clinic enrollment.


2020 ◽  
pp. 001857872097389
Author(s):  
Colleen A. Cook ◽  
Victor Vakayil ◽  
Kyle Pribyl ◽  
Derek Yerxa ◽  
John Kriz ◽  
...  

Purpose: Hospital pharmacists contribute to patient safety and quality initiatives by overseeing the prescribing of antidiabetic medications. A pharmacist-driven glycemic control protocol was developed to reduce the rate of severe hypoglycemia events (SHE) in high-risk hospitalized patients. Methods: We retrospectively analyzed the rates of SHE (defined as blood glucose ≤40 mg/dL), before and after instituting a pharmacist-driven glycemic control protocol over a 4-year period. A hospital glucose management team that included a lead Certified Diabetes Educator Pharmacist (CDEP), 5 pharmacists trained in diabetes, a lead hospitalist, critical care and hospital providers established a process to first identify patients at risk for severe hypoglycemia and then implement our protocol. Criteria from the American Diabetes Association and the American Association of Clinical Endocrinologists was utilized to identify and treat patients at risk for SHE. We analyzed and compared the rate of SHE and physician acceptance rates before and after protocol initiation. Results: From January 2015 to March 2019, 18 297 patients met criteria for this study; 139 patients experienced a SHE and approximately 80% were considered high risk diabetes patients. Physician acceptance rates for the new protocol ranged from 77% to 81% from the year of initiation (2016) through 2018. The absolute risk reduction of SHE was 9 events per 1000 hospitalized diabetic patients and the relative risk reduction was 74% SHE from the start to the end of the protocol implementation. Linear regression analysis demonstrated that SHE decreased by 1.5 events per 1000 hospitalized diabetic patients (95% confidence interval, −1.54 to −1.48, P < .001) during the 2 years following the introduction of the protocol. This represents a 15% relative reduction of SHE per year. Conclusion: The pharmacist-driven glycemic control protocol was well accepted by our hospitalists and led to a significant reduction in SHE in high-risk diabetes patient groups at our hospital. It was cost effective and strengthened our physician-pharmacist relationship while improving diabetes care.


2020 ◽  
Vol 211 ◽  
pp. 108329 ◽  
Author(s):  
Maria O. López-Oliva ◽  
Virginia Martínez ◽  
Aranzazu Rodríguez-Sanz ◽  
Laura Álvarez ◽  
M. José Santana ◽  
...  

2020 ◽  
Vol 4 (7) ◽  
pp. 1526-1537
Author(s):  
David R. Gruber ◽  
Amanda L. Richards ◽  
Heather L. Howie ◽  
Ariel M. Hay ◽  
Jenna N. Lebedev ◽  
...  

Abstract Antibodies are typically thought of as the endpoint of humoral immunity that occur as the result of an adaptive immune response. However, affinity-matured antibodies can be present at the initiation of a new immune response, most commonly because of passive administration as a medical therapy. The current paradigm is that immunoglobulin M (IgM), IgA, and IgE enhance subsequent humoral immunity. In contrast, IgG has a “dual effect” in which it enhances responses to soluble antigens but suppresses responses to antigens on red blood cells (RBCs) (eg, immunoprophylaxis with anti-RhD). Here, we report a system in which passive antibody to an RBC antigen promotes a robust cellular immune response leading to endogenous CD4+ T-cell activation, germinal center formation, antibody secretion, and immunological memory. The mechanism requires ligation of Fcγ receptors on a specific subset of dendritic cells that results in CD4+ T-cell activation and expansion. Moreover, antibodies cross-enhance responses to a third-party antigen, but only if it is expressed on the same RBC as the antigen recognized by the antibody. Importantly, these observations were IgG subtype specific. Thus, these findings demonstrate that antibodies to RBC alloantigens can enhance humoral immunity in an IgG subtype-specific fashion and provide mechanistic elucidation of the enhancing effects.


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