Evaluation of pretransplant influenza vaccination in hematopoietic SCT: a randomized prospective study.

Pretransplant influenza vaccination of the donor or allogeneic hematopoietic SCT (HSCT) candidate was evaluated in a randomized study. One hundred and twenty-two HSCT recipients and their donors were assigned to three randomization groups: no pretransplant vaccination (n=38), donor pretransplant vaccination (n=44) or recipient pretransplant vaccination (n=40). Specific IgG was assessed by both hemagglutinin inhibition (HI) and, in 57 patients, by an indirect influenza-specific ELISA at specified times after HSCT. Vaccinated donors had seroprotective HI titers for Ags H1 and H3 (P<0.001) compared with the other groups at the time of donation. The titers against H1 (P=0.028) and H3 (P<0.001) were highest in the pretransplant recipient vaccination group until day 180 after transplantation. A significant difference was found in the specific Ig levels against pandemic H1N1 at 6 months after SCT (P=0.02). The mean IgG levels against pandemic H1N1 and generic H1N1 and H3N2 were highest in the pretransplant recipient vaccination group. We conclude that pretransplant recipient vaccination improved the influenza-specific seroprotection rates.

An outbreak of respiratory syncytial virus infection in hematopoietic stem cell transplantation outpatients: good outcome without specific antiviral treatment.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in hematopoietic stem cell transplantations (HSCT) patients. The efficacy of treatment, however, remains controversial. We describe an outbreak of 31 cases of RSV that occurred in an HSCT outpatient care unit in the fall season from March through May 2010, with a good outcome without any specific antiviral treatment. METHODS: During these 3 months, 222 nasal wash samples were tested and, of these, 31 outpatients were positive for RSV. In 2009, 99 samples had been tested and only 10 outpatients were positive for RSV in the same period. RESULTS: Seven (22.5%) patients had severe neutropenia (<500 cells/µL); severe lymphopenia (<200 cells/µL) was present in 13 (41.9%) patients, and 14 (45%) had received intravenous broad-spectrum antibiotics. Hospitalization was necessary only for 8 patients (25.8%); 20 had lower respiratory tract infection (64.5%). Only 1 patient died as a result of proven invasive aspergillosis. CONCLUSION: This report suggests that HSCT outpatients with no risk factors may not always require specific treatment for RSV.

Loss of hepatitis A virus antibodies after bone marrow transplantation.

Reimmunization guidelines have recommended the inactivated HAV vaccine for hematopoietic stem cell transplant (HSCT) recipients living in or traveling to areas where hepatitis A is endemic. As a shift from high to medium hepatitis A endemicity has been observed in several countries in Latin America, we conducted a retrospective study to evaluate the prevalence of hepatitis A pre-bone marrow transplant (BMT) and the loss of specific antibodies in consecutive stored serum samples from 77 BMT recipients followed up from 82 to 1530 days. The prevalence of HAV antibodies was 92.2% before BMT. As vaccine was not available in Brazil when the samples were taken, it was assumed that this prevalence reflects natural infection. Survival analysis showed that the probability of becoming seronegative was 4.5% (+/-2.6%), 7.9% (+/-3.4%), 10.1% (+/-4.0%), 23.4% (+/-9.6%) at 1, 2, 3 and 4 years after transplant, respectively. The loss of HAV antibodies was significantly associated with longer follow-up (P=0.0015), younger age (P=0.049) and acute graft-versus-host disease (P=0.035). As most reimmunization protocols start around day +365, in developing countries with similar HAV endemicity, BMT recipients should have serological screening before HAV vaccination and the inactivated vaccine should be advised to those seronegative.

The benefit of influenza vaccination after bone marrow transplantation.

Influenza vaccine is recommended yearly for recipients after the sixth month of BMT. Although a higher risk of complications of influenza is expected to occur in BMT patients, no study has addressed the clinical efficacy of influenza vaccination in this setting. Focusing on the clinical benefits of influenza vaccination, we evaluated the risk factors for influenza infection in a cohort of 177 BMT recipients followed up for 1 year. Influenza was diagnosed in 39 patients. Multivariate analyses showed that seasonal exposure and more aggressive conditioning regimens were independently associated with increased risk for influenza. Influenza vaccination and steroid use showed a protective role. Of the 43 patients who had received BMT longer than 6 months, 19 were vaccinated (compliance rate = 44.2%) and vaccine efficacy was 80%. We conclude that influenza vaccination plays an important role in protecting BMT recipients against influenza and all efforts should be made to ensure good compliance with vaccination.

Use of Oseltamivir to control influenza complications after bone marrow transplantation.

Influenza infection can be severe in bone marrow transplant (BMT) recipients. Although yearly epidemics occur worldwide, and a higher risk of complication is expected in these patients, few studies have addressed the impact of the new neuraminidase inhibitors in the prognosis of influenza after BMT. Influenza A or B infections were found in 39 of the 66 patients (59%) showing a positive nasal wash by DFA. Influenza A was diagnosed in 18 patients and influenza B in 23 patients; two patients were infected by influenza A and B with 84- and 90-day intervals between episodes, respectively. Of the 41 episodes (61%) of influenza A or B, 25 infections occurred during the spring and summer months. Oseltamivir was introduced within 48 h of symptoms appearing. Only two patients (5.1%) developed influenza pneumonia, and no patient died of influenza. A total of 22 patients (56.4%) acquired influenza before day +180 when preventive vaccination strategies are precluded owing to poor immunogenicity of the vaccine during this period. Oseltamivir proved to be safe and appears to have played an important role in the outcome of influenza infection in this population. The therapeutic and/or prophylactic benefits of Oseltamivir in BMT recipients remain to be demonstrated in randomized, prospective trials.

Low mortality rates related to respiratory virus infections after bone marrow transplantation.

Respiratory viruses (RVs) frequently cause severe respiratory disease in bone marrrow transplant (BMT) recipients. To evaluate the frequency of RV, nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection (URI). Direct immunofluorescence assay was performed for respiratory syncytial virus (RSV), influenza (Flu) A and B, adenovirus and parainfluenza (Paraflu) virus. Patients with RSV pneumonia or with upper RSV infection, but considered at high risk for developing RSV pneumonia received aerosolized ribavirin. Oseltamivir was given to patients with influenza. A total of 179 patients had 392 episodes of URI. In all, 68 (38%) tested positive: RSV was detected in 18 patients (26.4%), Flu B in 17 (25%), Flu A in 11 (16.2%) and Paraflu in 7 (10.3%). A total of 14 patients (20.6%) had multiple RV infections or coinfection. RSV pneumonia developed in 55.5% of the patients with RSV-URI. One of the 15 patients (6.6%) with RSV pneumonia died. Influenza pneumonia was diagnosed in three patients (7.3%). RSV and influenza infections peaked in fall-winter and winter-spring months, respectively. We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia. The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in randomized trials.

Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT.

Late CMV disease remains a major concern in allogeneic BMT recipients. Few surveillance data are available on the occurrence of CMV infection and recurrences after day +100. We evaluated the occurrence of antigenemia (AG) recurrences until day +365 in 76 patients who received pre-emptive ganciclovir (GCV) therapy prompted by AG > or = 2 positive cells. Sixty-two episodes of AG recurrences were detected in 33 of the 52 patients who had positive AG. Survival analysis showed a 45.4% probability of AG recurrence on day +100, 64.8% on day +180 and 71.2% on day +365. The median time for AG recurrences was 113 (35 to 343) days. Thirty-five of the 62 episodes (56.4%) occurred after day +100. More than 70% of the patients responded to a 2-week course of GCV and no CMV disease was observed shortly after discontinuation of GCV. The Cox proportional model showed a significant effect of AG recurrences on patient's follow-up only when the patient developed chronic GVHD (P = 0.012). Extended surveillance favored early introduction of GCV and late CMV pneumonia occurred in only one of the 76 patients (1.3%). AG recurrences are frequent after day +100 and extended surveillance until day +365 is recommended for patients who develop chronic GvHD.

CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy.

The incidence, treatment and outcome of CMV interstitial pneumonia (CMV-IP) were reviewed in 139 consecutive allogeneic BMT patients undergoing extended CMV antigenemia surveillance and two different ganciclovir (GCV) strategies to control CMV infection. Nineteen cases of CMV-IP were reviewed, 16 of 63 patients (25.4%) who received early GCV treatment (ET) and three of 76 patients (3.9%) who received preemptive (PE) GCV therapy. In the ET group, the median time for occurrence of CMV-IP was 55 (range 36 to 311) days. Two patients had three episodes of CMV-IP recurrences after day +100. CMV-IP-related death occurred in two patients (15.4%). In the PE group, 41 patients received pre-emptive GCV therapy prompted by the appearance of positive antigenemia > or =2 cells. The median time for the occurrence of CMV-IP was 92 (range 48 to 197) days. Response to therapy was observed when GCV was introduced within 6 days of antigenemia positivity. The use of IVIg in association with GCV did not play a major role in response to therapy. The median time for occurrence of CMV-IP was delayed during PE strategy and the cost-effectiveness of CMV surveillance after day +100 should be investigated in this population.

Administration of live attenuated varicella vaccine to children with cancer before starting chemotherapy.

From July 1985 to February 1987, of 46 consecutive children with cancer (26 male, 20 female; median age, 4 years) with no prior history of chickenpox, the initial 30 patients were randomized either to receive or not to receive live attenuated varicella vaccine (LAVV) before chemotherapy was started and the remaining 16 patients were all immunized without randomization. Before immunization, Varicella zoster (VZ) antibodies were detected by immunofluorescence and ELISA in 11 (34%) of 32 vaccinated children and two (14%) of 14 controls, indicating previous infection. A booster effect was evident in 70% of them and no side effects were noted. Ten (28%) of 32 vaccinees were excluded from the analysis because of early death due to cancer (1-4 weeks). Seroconversion was demonstrated in ten (77%) of 13 vaccinees, with high antibody titres. Only three of them lost their antibodies 2 years after immunization, as disclosed by serological follow-up. Eight out of 13 vaccinees had household contacts with VZ and none became infected. Zoster immunoglobulin (ZIG) was never given. Among controls, seven out of 14 were exposed to VZ and four (57%) became infected. Mild side effects were observed in four (12.5%) out of 32 vaccinees (three with papulovesicular rash, 6-30 lesions, and one with a 3-day intermittent fever). Local reactions, zoster and spreading of vaccinal virus did not occur. LAVV proved to be safe and effective when administered before starting chemotherapy to children with cancer and no history of varicella.

Infecção pelo citomegalovirus em pacientes com sindrome da imunodeficiencia adquirida (AIDS): relacoes clinico-virologicas e anatomopatologicas / Infection by cytomegalovirus in patients with acquired immunodeficiency syndrome (AIDS): clinical, virological and histopathological correlations

Com o objetivo de determinar a prevalencia da infeccao pelo Citomegalovirus (CMV) em pacientes com AIDS, bem como relacionar os achados clinicos virologicos decorrentes desta infeccao com as repercussoes anatomopatologicas, estudamos 50 pacientes adultos atendidos entre abril de 1986 a junho de 1987, em dois hospitais publicos de Sao Paulo (HSP e HSPE). Estes pacientes foram acompanhados clinica e laboratorialmente, por periodo medio de 2 meses com coletas seriadas de sangue, urina e saliva. Foram realizados isolamento do CMV em monocamadas de fibroblastos humanos e testes sorologicos de Imunofluorescencia Indireta (IFI-IgG/IgM) e Reacao Imunoenzimatica (ELISA-IgG). No momento da admissao no estudo 20 por cento (10/50) dos pacientes apresentavam anticorpos IgM CMV especificos e 100 por cento (50/50) deles anticorpos IgG (IFI). Durante o acompanhamento, 5 pacientes inicialmente IgM negativos tornaram-se IgM positivos, sugerindo reativacao ou reinfeccao pelo CMV. O CMV foi isolado de sangue periferico em 12,5 por cento, da urina em 23,2 por cento, da saliva em 21,9 por cento dos pacientes. Exames anatomopatologicos foram realizados em 24 pacientes, correspondendo a 60 por cento dos pacientes que evoluiram para obito durante o periodo de estudo...

Infecção perinatal pelo citomegalovirus em hospital publico do municipio de Sao Paulo: estudo prospectivo / Perinatal infection due to cytomegaloviruses in a public hospital of the municipality of Säo Paulo: a prospective study

Com o objetivo de se avaliar a magnitude da infeccao perinatal pelo citomegalovirus em hospital publico do municipio de Sao Paulo, os autores acompanharam prospectivamente 98 recem-nascidos ete o quarto mes de vida. Amostras de urina foram coletadas ao nascimento e posteriormente a cada mes, para inoculacao em tubos contendo fibroblastos humanos. Amostras de sangue foram coletadas ao nascimento, no segundo e quarto mes de vida para pesquisa de anticorpos IgM especificos para o CMV, pelo metodo de imunofluorescencia indireta. Dos 37 recem-nascidos que foram acompanhados ate o quarto mes de vida, 9 se infectaram neste periodo, com diagnostico feito pelo isolamento do CMV. O risco de aquisicao da infeccao pelo citomegalovirus no periodo perinatal estimado pela tabua de sobrevivencia foi de 30,9 por cento. A pesquisa de anticorpos IgM por imunofluorescencia so permitiu tal diagnostico em 2 casos (8,1 por cento). A diferenca observada entre os dois metodos foi estatisticamente significante (p = 0,015). O estudo da prevalencia de anticorpos IgG pelo ensaio imunoenzimatico nas maes das criancas mostrou taxas de 92,7 por cento. Nao se isolou CMV nas amostras de leite materno, coletadas mensalmente ate o terceiro mes de lactacao...

Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients.

From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV) was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.

Sindrome "mononucleose simile" na infancia. Incidencia da infeccao por citomegalovirus diagnosticada atraves de deteccao imunoenzimatica de anticorpos IgM. / Mononucleosis-like syndrome in childhood. Incidence of cytomegalovirus infection diagnosed by immunoenzymatic detection o IgM antibodies

Testando anticorpos IgM anti-citomegalovirus, pela tecnica imunoenzimatica ELISA, em 82 criancas com doenca "mononucleose simile" (reacao de Paul-Bunnell-Davidsohn negativa), os Autores diagnosticaram 5 casos (6%) de infeccao aguda por este agente. A presenca de linfonodomegalia cervical e exsudato de amigdalas em alguns destes pacientes sugere que a apresentacao clinica da citomegalomononucleose na infancia poderia, por vezes, ser distinta da forma classica do adulto