Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection.

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.

Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study.

BACKGROUND: Pulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively. METHODS: Sixty patients were prospectively enrolled (age 11 [7-16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63-0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio. RESULTS: Viral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36-0.50) in patients who were positive versus 0.34 (0.30-0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates. CONCLUSIONS: Patients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.

Dengue Virus Serotype 2 Intrahost Diversity in Patients with Different Clinical Outcomes.

Intrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus's dynamics within its human host.

Nucleoprotein-based ELISA for detection of SARS-COV-2 IgG antibodies: Could an old assay be suitable for serodiagnosis of the new coronavirus?

OBJECTIVES: We evaluated the performance of a nucleoprotein-based enzyme-linked immunosorbent assay (ELISA) for detection of IgG antibodies to SARS-CoV-2. METHODS: The ELISA was based on serum IgG reactivity to a 46-kDa protein derived from the recombinant SARS-CoV2 nucleoprotein. Assay sensitivity was assessed using serum samples from 134 COVID-19 confirmed cases obtained > 15 days after symptom onset. Specificity was determined by testing sera from 94 healthy controls. Cross-reactivity was evaluated with sera from 96 individuals with previous dengue or zika virus-confirmed infections, with 44 sera from individuals with confirmed infections to other respiratory viruses or with bacterial and fungal infections that cause pneumonia and with 40 sera negative for SARS-CoV-2 nucleoprotein by commercial ELISA kits. RESULTS: The majority of subjects were male and ≥ 60 years old. Assay sensitivity was 90.3 % (95 % confidence interval 84.1 %-94.2 %) and specificity was 97.9 % (92.6 %-99.4 %). There was no cross-reactivity with sera from individuals diagnosed with dengue, zika virus, influenza virus, rhinovirus, adenovirus, respiratory syncytial virus, seasonal coronavirus, Mycobacterium tuberculosis, Staphylococcus (S. aureus and coagulase-negative), Streptococcus pneumoniae, Klebsiella pneumoniae and the fungus Aspergillus fumigatus. The level of concordance of our test with results from commercial ELISA kits was 100 %. CONCLUSION: The nucleoprotein-based ELISA was specific for detection of IgG anti-nucleoprotein antibodies to SARS-CoV-2. It utilizes a frequently employed low expense assay protocol and is easier to perform than other currently available commercial SARS-CoV2 antibody detection tests.

Serum levels of proinflammatory cytokines in painful knee osteoarthritis and sensitization.

Osteoarthritis (OA) is the most common joint disorder in the world. Among the mechanisms involved in osteoarthritis, biomarkers (cytokines profile) may be related to pain and pain intensity, functional capacity, and pressure pain thresholds (PPT). Thus, the study of these relationships may offer useful information about pathophysiology and associated mechanisms involved in osteoarthritis. Therefore, the objective of this study was to investigate the seric concentration of pro (IL-6, IL-8, and TNF-α) and anti-inflammatory (IL-10) cytokines in patients with painful knee osteoarthritis and to correlate the levels of these biomarkers with the patients' functional capacity and pressure pain threshold (PPT) values.

A double-blinded, prospective study to define antigenemia and quantitative real-time polymerase chain reaction cutoffs to start preemptive therapy in low-risk, seropositive, renal transplanted recipients.

BACKGROUND: Cytomegalovirus (CMV) disease occurs in 16% to 20% of low-risk, CMV-positive renal transplant recipients. The cutoffs for quantitative real-time polymerase chain reaction (qPCR) or phosphoprotein (pp65) antigenemia (pp65emia) for starting preemptive therapy have not been well established. METHODS: We measured qPCR and pp65emia weekly from day 7 to day 120 after transplantation, in anti-CMV immunoglobulin G­positive donor and recipient pairs. Patients and physicians were blinded to the test results. Suspicion of CMV disease led to the order of new tests. In asymptomatic viremic patients, the highest pp65emia and qPCR values were used, whereas we considered the last value before diagnosis in those with CMV disease. RESULTS: We collected a total of 1,481 blood samples from 102 adult patients. Seventeen patients developed CMV disease, 54 presented at least one episode of viremia that cleared spontaneously, and 31 never presented viremia. Five patients developed CMV disease after the end of the study period. The median (95% confidence interval) pp65emia and qPCR values were higher before CMV disease than during asymptomatic viremia (6 [9­82] vs. 3 [1­14] cells/10(6) cells; P<0.001 and 3,080 [1,263­15,605] vs. 258 [258­1,679] copies/mL; P=0.008, respectively). The receiver operating characteristic curve showed that pp65emia 4 cells/10(6) cells or greater showed a sensitivity and specificity to predict CMV disease of 69% and 81%, respectively (area, 0.769; P=0.001), with a positive predictive value of 37% and a negative predictive value of 93%. For qPCR 2,000 copies/mL or higher, the positive predictive value and negative predictive value were 57% and 91%, respectively (receiver operating characteristic area, 0.782; P=0.000). CONCLUSION: With these cutoffs, both methods are appropriate for detecting CMV disease.

Identification of respiratory virus in infants with congenital heart disease by comparison of different methods.

Respiratory virus infections are the main cause of infant hospitalization and are potentially severe in children with congenital heart disease (CHD). Rapid and sensitive diagnosis is very important to early introduction of antiviral treatment and implementation of precautions to control transmission, reducing the risk of nosocomial infections. In the present study we compare different techniques in the diagnosis of respiratory viruses in CHD infants. Thirty-nine samples of nasopharyngeal aspirate were obtained from CHD infants with symptoms of respiratory infection. The Multiplex PCR (Seeplex® RV 12 ACE Detection) driven to the detection of 12 respiratory viruses was compared with the direct immunofluorescence assay (DFA) and PCR, both targeting seven respiratory viruses. The positivity found by DFA, Multiplex and PCR was 33.3%, 51.3% and 48.7%, respectively. Kappa index comparing DFA and Multiplex, DFA and PCR and PCR and Multiplex PCR was 0.542, 0.483 and 0.539, respectively. The concordance between techniques was considered moderate. Both Multiplex PCR (p = 0.001) and PCR (p = 0.002) detected significantly more respiratory virus than DFA. As the performance of the tests may vary, the combination of two or more techniques may increase diagnostic sensitivity favoring the diagnosis of co-infections, early introduction of antiviral therapy and implementation of appropriate measures.

Identification of respiratory virus in infants with congenital heart disease by comparison of different methods / Identificação de vírus respiratórios em crianças com cardiopatia congênita por comparação de diferentes métodos

Respiratory virus infections are the main cause of infant hospitalization and are potentially severe in children with congenital heart disease (CHD). Rapid and sensitive diagnosis is very important to early introduction of antiviral treatment and implementation of precautions to control transmission, reducing the risk of nosocomial infections. In the present study we compare different techniques in the diagnosis of respiratory viruses in CHD infants. Thirty-nine samples of nasopharyngeal aspirate were obtained from CHD infants with symptoms of respiratory infection. The Multiplex PCR (Seeplex® RV 12 ACE Detection) driven to the detection of 12 respiratory viruses was compared with the direct immunofluorescence assay (DFA) and PCR, both targeting seven respiratory viruses. The positivity found by DFA, Multiplex and PCR was 33.3 percent, 51.3 percent and 48.7 percent, respectively. Kappa index comparing DFA and Multiplex, DFA and PCR and PCR and Multiplex PCR was 0.542, 0.483 and 0.539, respectively. The concordance between techniques was considered moderate. Both Multiplex PCR (p = 0.001) and PCR (p = 0.002) detected significantly more respiratory virus than DFA. As the performance of the tests may vary, the combination of two or more techniques may increase diagnostic sensitivity favoring the diagnosis of co-infections, early introduction of antiviral therapy and implementation of appropriate measures.

Infecções respiratórias virais são a principal causa de hospitalização infantil e podem ser extremamente graves em crianças com cardiopatia congênita. O diagnóstico rápido e sensível é importante para a introdução precoce de tratamento antiviral e implantação de precauções para controle da transmissão, reduzindo o risco de infecções nosocomiais. Neste estudo, comparamos o desempenho de diferentes técnicas no diagnóstico de vírus respiratórios em crianças com cardiopatia congênita e sintomas respiratórios. Trinta e nove amostras de aspirado de nasofaringe foram obtidas de crianças com sintomas de infecção respiratória. Ensaio de PCR Multiplex que detecta 12 vírus respiratórios (Seeplex® RV 12 ACE Detection) foi comparado à Imunofluorescência Direta (IFD) e à PCR específica, ambas direcionadas a sete vírus. A positividade da IFD foi 33,3 por cento, do Multiplex foi 51,3 por cento e da PCR 48,7 por cento. O índice kappa comparando IFD e Multiplex, IFD e PCR, e PCR e Multiplex foi, respectivamente, 0,542, 0,483 e 0,539, sendo a concordância considerada moderada. O Multiplex e a PCR detectaram significantemente mais vírus que a IFD (p < 0,0001 e 0,002, respectivamente). Como o desempenho dos testes varia o uso de mais de uma técnica pode aumentar a sensibilidade diagnóstica favorecendo a introdução precoce de terapia antiviral e implantação de medidas profiláticas.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature / Complicações neurológicas causadas pelo citomegalovírus em pacientes com AIDS: estudo retrospectivo de 13 casos e revisão da literatura

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69 percent) were men. At admission all patients were aware of their HIV status and only four (31 percent) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62 percent) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62 percent), polyradiculopathy (n = 7; 54 percent), focal encephalitis (rhombencephalitis) (n = 1; 8 percent), and ventriculo-encephalitis (n = 1; 8 percent). Seven (54 percent) patients presented extra-neural CMV disease and four (31 percent) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38 percent. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50 percent) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20 percent). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

As complicações neurológicas causadas pelo Citomegalovírus (CMV) em pacientes com aids são raramente relatadas na era HAART. O objetivo deste estudo foi descrever as principais características clínicas e laboratoriais de pacientes com complicações neurológicas associadas ao CMV em pacientes com aids admitidos em centro de referência em Sao Paulo, Brasil. A doença citomegálica precisou da identificação do vírus no líquor mediante a reação em cadeia da polimerase (PCR). Treze casos foram identificados entre janeiro de 2004 e dezembro de 2008. A mediana da idade foi 38 anos e nove (69 por cento) eram homens. Na admissão, todos os pacientes sabiam do seu status sorológico para o HIV e apenas quatro (31 por cento) pacientes usavam HAART. A doença citomegálica foi a primeira doença definidora de aids em oito (62 por cento) pacientes. As síndromes neurológicas identificadas foram: encefalite difusa (n = 7; 62 por cento), polirradiculopatia (n = 7; 54 por cento), encefalite focal (romboencefalite) (n = 1; 8 por cento), e ventrículo-encefalite (n = 1; 8 por cento). Sete (54 por cento) pacientes apresentaram doença citomegálica fora do sistema nervoso e quatro (31 por cento) tiveram retinite. A mediana da contagem de células CD4+ foi 13 células/µL. A mortalidade global durante a internação foi 38 por cento. Oito pacientes usaram ganciclovir ou foscarnet (mortalidade: 50 por cento) e cinco pacientes usaram ganciclovir e foscarnet (mortalidade: 20 por cento). Nenhum paciente apresentou critérios diagnósticos da síndrome inflamatória de reconstituição imunológica. Quatro pacientes foram perdidos do acompanhamento ambulatorial e três pacientes apresentaram reconstituição imunológica e descontinuaram as profilaxias secundárias. Embora raras, as particulares síndromes neurológicas causadas pelo CMV continuam causando elevada mortalidade em pacientes com aids. A sobrevida depende do uso de terapia antiviral efetiva contra o CMV e a introdução oportuna do HAART.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature.

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69%) were men. At admission all patients were aware of their HIV status and only four (31%) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62%) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62%), polyradiculopathy (n = 7; 54%), focal encephalitis (rhombencephalitis) (n = 1; 8%), and ventriculo-encephalitis (n = 1; 8%). Seven (54%) patients presented extra-neural CMV disease and four (31%) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38%. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50%) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20%). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

Molecular characterization of strains of respiratory syncytial virus identified in a hematopoietic stem cell transplant outpatient unit over 2 years: community or nosocomial infection?

Respiratory syncytial virus (RSV) is recognized as the leading cause of nosocomial respiratory infection among hematopoietic stem cell transplant (HSCT) recipients, causing considerable morbidity and mortality. RSV is easily transmitted by contact with contaminated surfaces, and in HSCT units, more than 50% of RSV infections have been characterized as of nosocomial origin. From April 2001 to October 2002, RSV was identified by direct immunofluorescent assay in 42 symptomatic HSCT recipients. Seven RSV strains from 2001 and 12 RSV strains from 2002 were sequenced. RNA extraction, cDNA synthesis, and seminested polymerase chain reaction (PCR) with primers complementary to RSV genes G and F were performed. PCR products were analyzed by nucleotide sequencing of the C-terminal region of gene G for typing (in group A or B). Of the 7 strains analyzed in 2001, only 2 belonged to group B; the other 5 belonged to group A. Of these 7 strains, 3 were identical and were from recipients receiving outpatient care. In 2002, of the 12 strains analyzed, 3 belonged to group A and the other 9 belonged to group B. Of these 9 strains, 7 were genetically identical and were also from recipients receiving outpatient care. Therefore, multiple strains of RSV cocirculated in the hematopoietic stem cell transplant units (ward and outpatient units) between 2001 and 2002. Nosocomial transmission was more likely to occur at the HSCT outpatient unit than in the HSCT ward. Infection control practices should also be implemented in the outpatient setting.

Respiratory syncytial virus rhinosinusitis in intensive care unit patients.

This study reported a case of rhinosinusitis for Respiratory Syncytial Virus in Intensive Care Unit patient. The settings were Intensive Care Unit at Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil. One female HIV-infected patient with respiratory failure and circulatory shock due to splenic and renal abscesses, who developed rhinosinusitis caused by RSV and bacteria. Respiratory viruses can play a pathogenic role in airways infection allowing secondary bacterial overgrowth.

Cytomegalovirus glycoprotein B genotypes and central nervous system disease in AIDS patients.

To investigate any association between cytomegalovirus glycoprotein B (CMV gB) subtypes and central nervous system (CNS) disease in AIDS patients, proportions of different gB genotypes detected in AIDS patients with CNS disease were compared with the gB genotypes detected in AIDS patients with no neurological disorder. The patients were matched by CD4+ cell counts. CMV was detected by PCR in cerebrospinal fluid (CSF) samples obtained from AIDS patients with CNS disease and from urine and saliva samples obtained from AIDS patients without CNS disease. CMV strains obtained were digested by restriction enzymes HinffI and RsaI to classify the genotypes. The CMV gB genotype was determined in 26 CSF samples. Of these, 11/26 (42.3%) typed as gB group 1, seven (26.9%) as gB2, four (15.4%) as gB3, and four (15.4%) as gB4. The CMV gB genotype frequency distribution in the 42 AIDS patients without CNS disease showed that 18/42 (42.8%) were classified as gB group 1, 10 (23.8%) as gB2, seven (16.6%) as gB3, and seven (16.6%) as gB4. In the present study, no association was found between CMV gB genotypes and CMV-related central nervous system disease.

Herpes simplex virus shedding in bone marrow transplant recipients during low-dose oral acyclovir prohylaxis

A 400mg dose twice-a-day oral acyclovir prophylaxis regimen was evaluated in 50 allogenic transplant recipients. Twenty (40 percent) patients experienced 24 episodes of herpes simplex virus (HSV) shedding; 17 (70.8 percent) occurring during prophylaxis. Thirteen of such episodes were asymptomatic and, in three, it was difficult to differentiate severe mucositis from viral lesions. In the remaining one, HSV pneumonia was suspected after a bronchoalveolar lavage (BAL) procedure performed in an attempt to early detection of cytomegalovirus (CMV). All cases responded to acyclovir therapy or dose adjustment suggesting that acyclovir resistance did not account for the occurrence of infection in our patients. These data demonstrated that oral acyclovir prophylaxis, 400mg dose twice-a-day, was inadequate to suppress viral shedding. The bronchoalveolar lavage procedure in a patient with HSV shedding could precipitate HSV spread to the lungs and the occurrence of pneumonia.

Cytomegalovirus infection in a day-care center in the municipality of São Paulo

The prevalence of antibodies against cytomegalovirus (CMV) and the incidence of CMV infection were tested in 98 children aged 5 to 36 months who attended the day-care center of a University hospital in São Paulo. At the beginning of the study the overall prevalence of anti-CMV IgG antibodies was 44 (43/98). Saliva and/or urine samples were obtained from 38 of the 43 children that were seropositive at the beginning of the study for isolation of the virus, and 52.6 of these children were found to excrete CMV in one of the two materials. Among the 37 children that were initially seronegative from whom it was possible to obtain a new blood sample 6 to 12 months later, 22 (59.5) presented seroconversion. The rate of viral excretion through urine or saliva from the children that seroconverted was 50. These results indicate that CMV infection is frequent and occurs early among the children who attend this day-care center. However, controlled studies using molecular epidemiology techniques are needed to define more precisely the role of day-care centers in CMV dissemination.

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

De janeiro de 1988 a janeiro de 1989 todos os pacients submetidos a transplante de coraçiao de medula óssea no Instituto do Coraçäo do Hospital das Clínicas da Faculdade de Medicina da Universidade de Siao Paulo foram estudados quanto à incidência e morbidade das infecçöes pós-transplante causadas por vírus do grupo herpes. Cinco recipientes de medula óssea e 5 transplantados cardíacos foram observados por um período médio de 4.2 meses após o transplante. Todos os pacientes tinham sorologia positiva para citomegalovírus (CMV) antes do transplantee 80% desenvolveram uma ou mais recorrências durante o período de observaçäo. Dos 12 episódios de infecçäo por CMV detectados neste estudo, 83% foram acompanhados por alteraçöes clínicas ou laboratoriais. Apenas um caso apresentou doença grave. A incidência de infecçöes causadas por vírus Herpes simplex (HSV) fossem reprsentadas por lesöes orais ou genitais, houve também umcaso de hepatite por HSV. Um dos 6 episódios de infecçäo, por HSV. Um dos 6 episódios de infecçäo, por HSV que foram tratados com aciclovir näo respondeu ao tratamento. Posteriormente, o paciente se beneficiou com o uso de ganciclovir. Todos os indivíduos apresentavam antes do transplante anticorpos anti-vírus da varicela zoster. Porém, näo houve nenhum caso de reativaçäo. Este estudo realça a importância do cocntrole diagnóstico ativo da infeccöes por herpes-vírus em pacientes transplantados. Tanto as infecçöes causadas por CMV como por HSV mostraram alta incidência e grande mortalidade indicando a necessidade de quimioprofilaxia

Detecçäo de anticorpos IgM nas infecçöes primárias e secundárias pelo citomegalovírus em pacientes submetidos a transplante renal / IGM antibodies detection in primary and secundary cytomegalovirus infections in patients submeted a renal transplantation

Foram acompanhados 27 pacientes submetidos a transplante renal para avaliaçäo do comportamento dos anticorpos IgM e IgG CMV-específicos. Dos 27 casos estudados, 17 (63,0%) tinham anticorpos IgG, detectados pela reaçäo de fixaçäo de complemento (RFC), antes de serem submetidos ao transplante, e 10 (37,0%) eram soro negativos. A pesquisa de anticorpos IgM (técnica de imunofluorescência indireta) foi negativa em todas as amostras pré-transplante. Num período de acompanhamento que variou de 28 a 425 dias (média de 115 dias) após o transplante, observou-se que 20 dos 27 (74,1%) apresentaram evidências sorológicas de infecçäo pelo CMV, ocorrendo a maioria dos casos (14/20,70%) em pacientes que já tinham anticorpos para o CMV antes do transplante. A pesquisa de anticorpos IgM CMV-específicos foi positiva em 12 dos 14 pacientes com evidências sorológicas de reinfecçäo ou reativaçäo da infecçäo pelo CMV, e em 100% (6/6) dos pacientes com infecçäo primária. Dentre os 10 pacientes acompanhados por mais de 4 meses, somente 1 (10%) negativou o IgM neste período