Endemic viral infections in immunocompromised hosts: Dengue, Chikungunya, Zika.

PURPOSE OF REVIEW: Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH). RECENT FINDINGS: Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections. SUMMARY: Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.

Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers.

PURPOSE: The prompt initiation of a betalactam antibiotic in febrile neutropenic patients is considered standard of care, while the empiric use of vancomycin is recommended by guidelines in specific situations, with a low level of evidence. The objective of this study was to assess the utilization of vancomycin in the management of febrile neutropenia within four Brazilian medical centers that implemented more stringent criteria for its administration. METHODS: A comprehensive retrospective analysis was performed encompassing all instances of febrile neutropenia observed during the period from 2013 to 2019. The primary focus was to identify the reasons for initiating vancomycin therapy. RESULTS: A total of 536 consecutive episodes of febrile neutropenia were documented, involving 384 patients with a median age of 52 years (range 18-86). Chemotherapy preceded febrile neutropenia in 59.7% of cases, while 40.3% occurred after hematopoietic stem cell transplantation. The most prevalent underlying diseases were acute myeloid leukemia (26.5%) and non-Hodgkin's lymphoma (22%). According to international guidelines, vancomycin should have been initiated at the onset of fever in 145 episodes (27%); however, it was administered in only 27 cases (5.0%). Three episodes were associated with Staphylococcus aureus bacteremia, two of which were methicillin resistant. The 15-day and 30-day mortality rates were 5.0% and 9.9%, respectively. CONCLUSIONS: The results of this study underscore the notably low utilization rate of vancomycin in cases of febrile neutropenia, despite clear indications outlined in established guidelines. These findings emphasize the importance of carefully implementing guideline recommendations, considering local epidemiological factors, especially when the strength of recommendation is weak.

Clinical outcome from hematopoietic cell transplant patients with bloodstream infection caused by carbapenem-resistant P. aeruginosa and the impact of antimicrobial combination in vitro.

Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored blaSPM-1 and Tn4371 and belonged to ST277. The synergistic effect in vitro with meropenem with colistin appeared to be a better therapeutic option.

Hepatitis B virus among hematopoietic stem cell transplant recipients: Antiviral impact in seroconversion, engraftment, and mortality in a Latin American center.

BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post-HSCT. METHODS: We performed a single-center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post-HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti-HBc or HBV-NAT), confirmed later on by a laboratory routine serology. RESULTS: A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty-six patients were confirmed to have HBV infection, of which six were HBsAg-positive, 20 were isolated anti-HBc-positive, and 60 had resolved infection (anti-HBc-positive and anti-HBs-positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg-positive, three were HBeAg-negative and HBV-DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir + lamivudine due to HIV co-infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50 years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV-DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft-versus-host disease or CMV reactivation also was not linked to increased mortality. CONCLUSIONS: To sum up, HBV serology, ALT, and HBV-DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2-year mortality post-transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation.

Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Pneumocystis jirovecii Pneumonia during Brentuximab Vedotin Therapy: A Case Report and Literature Review.

Brentuximab vedotin (BV), an antibody drug conjugate against CD30, has been increasingly used in clinical practice, and the less common adverse events associated to the drug are not well described. Also, opportunistic infections have been reported, and data on immune reconstitution after use of BV are lacking. The authors describe a case of a 45-year-old man with Hodgkin lymphoma receiving BV as a consolidation therapy after autologous hematopoietic stem cell transplant. After nine months of consolidation with BV, the patient developed a respiratory disorder characterized by fever, chills, dyspnea, and hypoxemia, and pneumonia by Pneumocystis jirovecii (PJ) was confirmed by bronchoscopy with bronchoalveolar lavage. In spite of the fact that there are no specific recommendations about infectious prophylaxis in patients using the drug, we would like to draw the attention of professionals who use the medication in relation to the risk of opportunistic infections, such as pneumonia by PJ.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

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.

Cytomegalovirus infection in transplant recipients.

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

Tuberculosis in hematopoietic stem cell transplant recipients.

Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50% and is higher in allogeneic HSCT than in autologous. There is no consensus regarding the screening with tuberculin skin test or QuantiFERON-TB gold, primary prophylaxis for latent TB, and whether the epidemiologic query should be emphasized in developing countries with high prevalence of TB.

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.

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. .