Vivian Iida Avelino-Silva

Liver transplant from Anti-HBc-positive, HBsAg-negative donor into HBsAg-negative recipient: is it safe? A systematic review of the literature.

Avelino‐Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti‐HBc‐positive, HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature. 
Clin Transplant 2010: 24: 735–746.

Liver transplantation: fifty years of experience.

Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation.

CD4/CD8 Ratio Predicts Yellow Fever Vaccine-Induced Antibody Titers in Virologically Suppressed HIV-Infected Patients.

Background:Yellow fever vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. Methods:We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4+ T-cell count, CD4+/CD8+ ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. Results:Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: −0.38, P = 0.027) and lower CD4+/CD8+ ratio (rho: 0.42, P = 0.014), but not CD4+ T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. Conclusions:ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4+/CD8+ ratio, but not with CD4+ T-cell count. These results supports the notion that low CD4+/CD8+ ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4+ T-cell count in patients with successful ART.

Campaign, counseling and compliance with influenza vaccine among older persons

OBJECTIVES: Population aging raises concerns regarding the increases in the rates of morbidity and mortality that result from influenza and its complications. Although vaccination is the most important tool for preventing influenza, vaccination program among high-risk groups has not reached its predetermined aims in several settings. This study aimed to evaluate the impacts of clinical and demographic factors on vaccine compliance among the elderly in a setting that includes a well-established annual national influenza vaccination campaign. METHODS: This cross-sectional study included 134 elderly patients who were regularly followed in an academic medical institution and who were evaluated for their influenza vaccination uptake within the last five years; in addition, the demographic and clinical characteristics and the reasons for compliance or noncompliance with the vaccination program were investigated. RESULTS: In total, 67.1% of the participants received the seasonal influenza vaccine in 2009. Within this vaccination-compliant group, the most common reason for vaccine uptake was the annual nationwide campaign (52.2%; 95% CI: 41.4–62.9%); compared to the noncompliant group, a higher percentage of compliant patients had been advised by their physician to take the vaccine (58.9% vs. 34.1%; p<0.01). CONCLUSION: The education of patients and health care professionals along with the implementation of immunization campaigns should be evaluated and considered by health authorities as essential for increasing the success rate of influenza vaccination compliance among the elderly.

A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus

The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut50 ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.

Sclerosing mesenteritis as an unusual cause of fever of unknown origin: a case report and review

Fever of unknown origin (FUO), defined as a temperature higher than 38.3°C on several occasions and lasting longer than three weeks that is associated with a diagnosis that remains uncertain after one week of investigation (1), is a frequent condition in the infectious diseases specialty clinic. The condition is often associated with extensive diagnostic procedures and, not rarely, frustration for both the patient and the physician. An evidence-based approach has been used to group the causes of FUO (2) into four general categories: infectious, rheumatic/inflammatory, neoplastic, and miscellaneous disorders (3). Infectious diseases such as endocarditis, intra-abdominal abscesses, and tuberculosis, as well as inflammatory conditions such as temporal arteritis, adults Still disease, and late-onset rheumatoid arthritis, are commonly identified causes of FUO (3). However, unexpected and rare causes are sometimes diagnosed, as reported below in a case of sclerosing mesenteritis.

CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients

Background HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity—may influence vaccine response in this population. Methods We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. Results 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV–infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. Conclusions HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

Disseminated Fusarium infection in autologous stem cell transplant recipient

Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.

Evolution of a Jellyfish Sting

A healthy 33-year-old woman was stung by a jellyfish on the medial aspect of her left ankle while wading in the coastal waters of North Carolina. Within hours, painful, erythematous, linear, urticarial lesions developed where the jellyfish tentacles had made contact with her skin.

Yellow fever vaccine viremia following ablative BM suppression in AML

Yellow fever vaccine (YFV) has been used for over 70 years in endemic areas. It is produced from 17D attenuated viral strain and is rarely associated with serious adverse events (SAE), such as anaphylaxis and YFV-associated neurotropic and viscerotropic diseases. Immunosuppressed patients and patients at extremes of age are at higher risk of developing YFV-associated adverse events (AE). The vaccine is not recommended for infants less than six months old or for persons with altered immune status such as thymic disorders, AIDS and immunosuppressive therapies based on a presumed increased risk for YFV-associated SAE. YFV should be deferred in persons with a history of cancer or transplant recipients until immune recovery, as suggested by two reports describing the lack of YFV AE in immune-recovered BM recipients. Mechanisms for YFV-associated neurotropic and viscerotropic diseases are still not completely elucidated. It is likely that immune response may not contain 17D replication, which usually follows the first vaccine dose. Indeed, a low-level viremia has been described in primary recipients, starting 3–7 days after vaccination, persisting for 1–3 days and decreasing as IgM Abs are produced. We report the case of a patient with AML who started chemotherapy just 7 days after yellow fever (YF) vaccination. 17D viral load was monitored by RT-PCR, as well as clinical and laboratory abnormalities. Levels of neutralizing Abs (NA) against 17D were also quantified. The titration of NA against YF was performed at Fiocruz, Rio de Janeiro, using a Plaque Reduction Neutralization Test in serial twofold dilutions starting at 1:5, in 50 mL aliquots of heatinactivated (56 1C for 30 min) serum, in 96-well tissue culture plates. A positive in house monkey serum sample with YF Ab content calibrated by a WHO International Reference Preparation, with 1115 mIU/mL was the reference for each set of tests, and was repeated every 10 samples. After incubation at room temperature for 1 h, a suspension of Vero cells was added and the plates were incubated for 3 h. The medium was then discarded and the cells overlaid with 100 mL of medium containing carboxymethylcellulose. After incubation for 7 days at 37 1C in 5% CO2, cell monolayers were fixed with 10% formalin, stained with 0.04% crystal violet and plaques counted. The mean Ab content at the 50% end point of the standard was calculated through linear regression. The mean titre of the standard sera determined the levels of protection in each sample. Total RNA was extracted from 140mL of plasma using QIAamp RNA Blood Mini Kit (Qiagen, Hilden, Germany) and eluted in 60 mL of elution buffer. cDNA was obtained through a reverse transcriptase reaction using 10 mL of the extracted RNA, 300 ng of random primer (Amersham Biosciences, Piscataway, NJ, USA); 10 U/mL of Super Script TM II reverse transcriptase (Invitrogen, Carlsbad, CA, USA) in a buffer solution with 0.25 U/mL of ribonuclease inhibitor (Invitrogen) and 0.5 mM deoxyribonucleotide triphosphates (Invitrogen), at final volume of 20 mL. The reaction was incubated at 45 1C for 90 min. Five microlitres of cDNA was added to 20mL of TaqMan Master Mix (Applied Biosystems, Foster City, CA, USA) and was amplified by RT-PCR using the following primers and probe: (YF-NS5_F) 50-GCACGG ATGTAACAGACTGAAGA-30; (YF-NS5_R) 50-CCAGGCCGAACCTGTC AT-30 and (YF-NS5Probe) 50-FAM-CGACTGTGTGGTCCGGCCCATC-30TAMRA. The product was amplified using optical detection system layout of BioRad ICycler for 45 cycles at the following settings: 10 min at 95 1C, followed by 45 cycles of 15 s for 94 1C and 60 s for 60 C. An asymptomatic 39 year-old man was diagnosed with AML after routine blood test. BM aspiration demonstrated 76% blasts, urging chemotherapy initiation. He had been vaccinated against YF for the first time 7 days before chemotherapy was started. Detailed clinical and laboratory follow up for possible YFVassociated AE was performed, and 17D viral load was monitored by RT-PCR, daily for the first 19 days after vaccination (Table 1). He remained clinically stable, without any neurological or hepatic abnormalities that could resemble YFV-associated neurotropic or viscerotropic disease. 17D viral load, as measured by RT-PCR, decreased progressively from the first measurement, with undetectable levels on day 16. NA against 17D were measured on day 28 after vaccination, and surprisingly indicated protective levels. This is an unusual case of YF vaccination followed by chemotherapy-induced severe immunosuppression. The 17D viremia was documented for 15 days after vaccination, and was not associated with detectable AE. Surprisingly, protective NA titers were detected 1 month after the vaccine, indicating memory B lymphocytes may have been preserved despite ablative BM suppression. The use of 17D in immunosuppressed patients is a common concern in clinical practice and several points remain unknown. In a recent review, 17D AE in vulnerable populations of children, pregnant women, older persons, HIV positive patients and in individuals taking immunosuppressive medications were described. Although SAE have been identified among older persons and breastfeeding mothers, no change in the current understanding of the risk of 17D SAE could be provided by this comprehensive review. Several inconclusive reports described mutations in 17D that may be associated with SAE. However, a particular strain related to the lack of AE in an immunosuppressed individual has not been described. Host genetic susceptibilities may also have an important role in the development of YFV AE. In previous reports, cases of YFV AE have been associated with high and prolonged 17D viral load, abnormalities in innate immune response and genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES. Populations of immunosuppressed individuals are likely to increase worldwide, raising concern about the use of live attenuated vaccines and their possible AE. YFV zones have been expanding in recent years in several regions of South America, in order to prevent potential urban outbreaks of the disease. Understanding viral and immune response dynamics following YFV in healthy and immunosuppressed persons is paramount to elucidate the mechanisms for YFV-associated neurotropic and viscerotropic diseases. Moreover, for immunosuppressed patients Bone Marrow Transplantation (2013) 48, 1008–1009 & 2013 Macmillan Publishers Limited All rights reserved 0268-3369/13