The Use of Two-Dimensional Strain Measured by Speckle Tracking in the Identification of Incipient Ventricular Dysfunction in HIV-Infected Patients on Antiretroviral Therapy, Untreated HIV Patients and Healthy Controls / O Uso do Strain Bidimensional Obtido pelo Speckle Tracking na Identificação da Disfunção Ventricular Incipiente em Pacientes Infectados pelo HIV em Uso de Terapia Antirretroviral, Pacientes HIV não Tratados e Controles Saudáveis

Abstract Background: Most cardiovascular abnormalities in patients infected with the human immunodeficiency virus (HIV) have been associated with myocardial damage directly caused by the virus. Some cases, however, may be associated with adverse effects from antiretroviral therapy (ART). New ventricular function assessment techniques are capable of detecting early changes in the cardiac function of HIV-infected patients using or not using ART. The usefulness of these techniques has been little employed in these patients. Objectives: To investigate the potential influence of antiretroviral therapy (ART) on the occurrence of subclinical left ventricular systolic dysfunction evaluated by myocardial strain rate analysis using two-dimensional speckle tracking echocardiography (2-D Echo) in treated HIV patients compared to untreated patients and healthy individuals. Methods: Sixty-eight HIV-infected patients with no cardiovascular symptoms, normal left ventricular (LV) ejection fraction (> 0.55 on 2-D Echo) were divided into three groups: 11 patients not using antiretroviral therapy (NT), 24 using protease inhibitor (PI) and 33 using non-nucleoside reverse transcriptase inhibitor (NNRTI). We also studied 30 normal non-HIV infected individuals (Ctrl). Demographic, clinical, biochemical and anthropometric data were collected. Preliminary transthoracic echocardiography included study of myocardial strain using two-dimensional speckle tracking. We studied strain and strain rate in the seventeen left ventricular (LV) myocardial segments in the longitudinal, circumferential and radial axes. Statistical analysis of the data was done with IBM SPSS - version 20 for Windows. Upon analysis of the data, namely the normality of independent variables in the different groups and the homogeneity of the variances between the groups, Kruskal-Wallis' non-parametric test was done, followed by Dunn's multiple comparison tests to test the significance of the differences between the values measured in the study groups. A significance level of 5% was adopted for decision-making on statistical tests. Results: The mean age of HIV patients was 40 ± 8.65 years and the mean age of controls was 50 ± 11.6 years (p < 0.001). Median LV global longitudinal strain (GLS) of NT patients (-17.70%), PI patients (-18.27%) and NNRTIs (-18.47%) were significantly lower than that of the Ctrl group (-20.77%; p = 0.001). There was no significant difference in mean SLG between treated patients (PI, NNRTI) and untreated (NT) patients. No significant differences were observed in mean circumferential and radial strain, nor on circumferential and radial strain rates between the NT, PI, NNRTI and Ctrl groups. Conclusion: The data suggest that HIV patients present, on myocardial strain measured by speckle tracking, signs of early LV systolic dysfunction that seem to be unrelated to the presence of ART. The prognostic significance of this condition in these patients deserves further studies.

Resumo Fundamento: A maior parte das alterações cardiovasculares dos pacientes infectados pelo vírus da imunodeficiência humana (HIV) tem sido associada ao dano miocárdico causado diretamente pelo vírus. Alguns casos, porém, podem estar associados a efeitos adversos da terapia antirretroviral (TARV). Novas técnicas de avaliação da função ventricular são capazes de detectar modificações precoces na função cardíaca do paciente infectado pelo HIV em uso ou não de TARV. A utilidade dessas técnicas tem sido pouco empregada nesses pacientes. Objetivos: Investigar possível influência da terapia antirretroviral (TARV) na ocorrência de disfunção sistólica ventricular esquerda subclínica avaliada pela análise da taxa de deformação miocárdica (strain) por meio do speckle tracking ao ecocardiograma bidimensional (E2D) em pacientes portadores do HIV tratados, comparados com pacientes não tratados e indivíduos saudáveis. Métodos: Sessenta e oito pacientes infectados pelo HIV assintomáticos do ponto de vista cardiovascular, com fração de ejeção do ventrículo esquerdo (VE) normal (>0,55 pelo E2D) foram divididos em três grupos: 11 pacientes sem tratamento antirretroviral (ST), 24 em uso de inibidor de protease (IP) e 33 em uso de inibidor de transcriptase reversa não nucleosídeo (ITRNN). Foram estudados também 30 indivíduos normais não infectados pelo HIV (Ctrl). Foram coletados dados demográficos, clínicos, bioquímicos e antropométricos. A ecocardiografia transtorácica foi realizada incluindo no estudo inicial o estudo da deformação miocárdica pela técnica bidimensional (speckle tracking). Estudamos o strain e a sua taxa de deformação (strain rate) nos dezessete segmentos miocárdicos do ventrículo esquerdo (VE) nos eixos longitudinal, circunferencial e radial. A análise estatística dos dados foi feita com o programa IBM SPSS - versão 20 para Windows. Depois de analisados os dados, nomeadamente a normalidade das variáveis independentes nos diferentes grupos e a homogeneidade das variâncias entre os grupos, decidiu-se utilizar o teste não paramétrico de Kruskal-Wallis seguido dos testes de comparações múltiplas pelo procedimento de Dunn, para testar a significância das diferenças entre os valores medidos nos grupos em estudo. Foi considerado o nível de significância de 5% para a tomada de decisão nos testes estatísticos realizados. Resultados: A média das idades dos pacientes com HIV foi de 40 ± 8,65 anos e a idade média dos controles foi de 50 ± 11,6 anos (p < 0,001). Os valores medianos do strain longitudinal global do VE (SLG) dos pacientes ST (-17.70%), dos pacientes IP (-18.27%) e ITRNN (-18.47%) foram significativamente menores do que o grupo Ctrl (-20,77%; p = 0,001). Não houve diferença significante nos valores médios do SLGentre os pacientes tratados (IP, ITRNN) e não tratados (ST). Não foram observadas diferenças significantes nos valores médios do strain circunferencial e radial, nem nas taxas de deformação circunferencial e radial entre os grupos ST, IP, ITRNN e Ctrl. Conclusão: Os dados sugerem que pacientes com HIV apresentam, à análise da deformação miocárdica ao speckle tracking, sinais de disfunção sistólica incipiente do VE que parece não ter relação com a presença de TARV. O significado prognóstico dessa alteração nesses pacientes merece estudos futuros.

Molecular diversity of human parvovirus B19 during two outbreaks of erythema infectiosum in Brazil

Abstract This study was conducted to provide information on the genetic diversity of human parvovirus B19 (B19V) circulating in the municipality of Niterói, Rio de Janeiro, Southeast Brazil during 1996-2006, a period with two distinct outbreaks of B19V infection: 1999-2000 and 2004-2005. A total of 27 sera from patients with erythema infectiosum and five sera from HIV-infected patients that tested positive for B19V DNA during the study period were analyzed. To genotype B19V strains, a semi-nested PCR for partial amplification of the capsid gene was performed and sequence analysis revealed that 31 sequences belonged to subgenotype 1a (G1a) of the main genotype 1 and one sequence was characterized as subgenotype 3b (G3b). The phylogenetic tree supported the division of the G1a into two well-defined clades with 1.3% of divergence. The low diversity of the G1a strains may be explained by the fact that all patients had acute B19V infection and 30/32 sera were collected during two distinct outbreaks. The G3b strain was from an HIV-infected patient who seroconverted to anti-B19 IgG antibodies in September/2005. This is the first report of G3b in the state of Rio de Janeiro.

Clinical features and laboratory findings of human parvovirus B19 in human immunodeficiency virus-infected patients

Immunocompromised patients may develop severe chronic anaemia when infected by human parvovirus B19 (B19V). However, this is not the case in human immunodeficiency virus (HIV)-infected patients with good adherence to highly active antiretroviral treatment (HAART). In this study, we investigated the clinical evolution of five HIV-infected patients receiving HAART who had B19V infections confirmed by serum polymerase chain reaction. Four of the patients were infected with genotype 1a strains and the remaining patient was infected with a genotype 3b strain. Anaemia was detected in three of the patients, but all patients recovered without requiring immunoglobulin and/or blood transfusions. In all cases, the attending physicians did not suspect the B19V infections. There was no apparent relationship between the infecting genotype and the clinical course. In the HAART era, B19V infections in HIV-positive patients may be limited, subtle or unapparent.

Parvovirus B19 seroconversion in a cohort of human immunodeficiency virus-infected patients

Erythrovirus B19 (B19V) infection may cause red cell aplasia in patients infected with human immunodeficiency virus (HIV). The introduction of highly active antiretroviral therapy (HAART) has improved the immune function of these patients by modifying the course of B19V infection. The purpose of this study was to estimate the frequency of B19 seroconversion in a cohort of HIV-infected patients and evaluate the occurrence of B19V-related anaemia during the seroconversion period. Adult HIV-infected patients were studied at a public hospital in Niterói, state of Rio de Janeiro, Brazil. IgG and IgM antibodies against B19V were detected by an enzyme-linked immunosorbent assay and B19 viraemia was assayed by polymerase chain reaction. Medical records were reviewed for any clinical evaluation of anaemia. Seroconversion was detected in 31.8% of the 88 individuals who began the study as anti-B19V IgG-negative. No clinical manifestations of B19V infection were detected during the period of seroconversion. Patients who seroconverted were 5.40 times more likely to have anaemia than those who did not [odds ratio 5.40 (95% confidence interval: 1.33-22.93)]. Anaemia was detected in eight patients. All patients recovered from anaemia by either beginning or continuing HAART, without requiring blood transfusions. In the HAART era, B19V infection may only be associated with a course of disease characterised by less severe chronic anaemia. This milder course of B19V-associated disease is likely due to the increased immune function of HAART-treated patients.

Toxoplasma gondii antibody profile in HIV-1-infected and uninfected pregnant women and the impact on congenital toxoplasmosis diagnosis in Rio de Janeiro, Brazil

OBJECTIVE: Compare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women. METHODS: This study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women. RESULTS: The average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL). CONCLUSIONS: Congenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation.

Congenital toxoplasmosis transmitted by human immunodeficiency-virus infected women

We report the occurrence of congenital toxoplasmosis in three infants born to HIV infected women who had high anti-toxoplasma IgG and negative IgM during pregnancy. We briefly reviewed available literature and discussed the possible transmission mechanisms of congenital toxoplasmosis among HIV infected pregnant women. Serum samples were tested for Toxoplasma gondii IgM and IgG antibodies using commercial enzyme immunoassay and IgG-avidity tests. In the first case, fetal death occurred at 28th week of gestation. In the second case, congenital toxoplasmosis was diagnosis at 6th month of life; and in the third case, an HIV-infected newborn, congenital toxoplasmosis was asymptomatic. These cases point out to the possibility of enhanced maternal-fetal transmission of T. gondii infection by HIV-infected women chronically infected, which may have important public health consequences, considering that increasing frequency of HIV-infection has been observed among women of childbearing age around the world.

Estudo clínico-epidemiológico da infecção pelo parvovírus humano B19 em pacientes infectados pelo HIV acompanhados no serviço de doenças infecciosas e parasitárias do Hospital Universitário Antonio Pedro - Niterói, RJ, no período de 2001 a 2008 / Clinical and epidemiological study of human parvovirus B19 infection in HIV-infected patients followed in the service of Infectious and Parasitic Diseases, University Hospital Antonio Pedro - Niterói, RJ, in the period 2001-2008

O parvovírus humano B19 (B19V) está relacionado a diferentes quadros clínicos, dentre eles a anemia crônica em pacientes infectados pelo vírus da imunodeficiência humana(HIV). Objetivos: Determinar a soroprevalência de anticorpos IgG anti B19V; estabelecer a frequência da soroconversão para B19V, identificar a ocorrência de anemioa prolongada nos pacientes que apresentaram soroconversão...A prevalência de anticorpos IgG anti B19V foi influenciada apenas pela carga viral do HIV, sendo mais elevada nos pacientes com carga viral do HIV , 10.000 cópias/mL. Dos 88 (31,8%) pacientes suscetíveis ao B19V, 31,8% adquiriram a infecção, principalmente durante os períodos epidêmicos. A soroconversão para o B19V não foi influenciada pelas variáveis estudadas e estava fortemente associada à anemia na última amostra negativa para IgG anti B19V. Anemia prolongada ocorreu em pelo menos 28,6% dos pacieentes que apresentaram soroconversão. A presença de anemia prolongada, especialmente durante epidemia de B19V, deve alertar o médico para a possibilidade de infecção pelo B19V. Na era da terapia antirretroviral altamente potente, e consequentemente reconstituição imune, a infecção pelo B19V pode cursar com anemia prolongada de menor gravidade.

Seroepidemiological study of human parvovirus B19 among human immunodeficiency virus-infected patients in a medium-sized city in Rio de Janeiro, Brazil

Parvovirus B19 (B-19) may cause chronic anaemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). We studied single serum samples from 261 consecutive HIV-infected patients using an enzyme immunoassay to detect IgG antibodies to B-19. The seroprevalence of B-19-IgG was 62.8 percent. The differences in seroprevalence across gender, age, educational categories, year of collection of the serum samples, clinical and antiretroviral therapy characteristics, CD4+ count, CD4+ and CD8+ percentage and CD4+/CD8+ ratios were neither substantial nor statistically significant. There was a non-significant, inverse association between B-19 seropositivity and plasma HIV load and haemoglobin level. Our results indicated that 37.1 percent of patients might be susceptible to B-19 infection and remained at risk for being infected, mainly during epidemic periods. As B-19 infection can be treated with immune globulin preparations, it may be included in the diagnostic approach toward chronic anaemia in HIV-infected patients.

Meningeal carcinomatosis as the initial manifestation of a gallbladder adenocarcinoma associated with a Krukenberg tumor

A case of malignant neoplasm is described in which the initial manifestations were mental dysfunction and meningeal irritation, mimicking chronic or subacute meningitis. Physical examination showed cranial nerve involvement and a pelvic tumor. There was progressive deterioration, and death occurred in 2 weeks. The autopsy revealed a gallbladder adenocarcinoma, meningeal carcinomatosis, and ovarian metastasis presenting as a Krukenberg tumor. The authors emphasize the importance of including meningeal carcinomatosis as a possibility in the differential diagnosis of non-characteristic clinical pictures, as well as the importance of the cerebrospinal fluid cytologic examination, repeated as needed, in order to confirm this diagnosis

Hepatite B na síndrome de imunodeficiência adquirida / Hepatitis B in the acquired immunodeficiency syndrome

Estudo retrospectivo de 73 pacientes portadores da Síndrome de Imunodeficiência Adquirida (SIDA) internados na Enfermaria de Doenças Infecciosas e Parasitárias do Hospital Antônio Pedro, Niterói, Brasil, no período de 10 de abril de 1985 a 10 de abril de 1993. Destes 73 pacientes, 52 (71,2 por cento) possuíam evidências sorológicas de infecçäo pelo vírus da hepatite B. Baseando-se em uma revisäo da literatura sobre as internaçöes da SIDA com a hepatite B e com outras doenças sexualmente transmissíveis (DST), foi feita uma análise do comportamento epidemiológico da hepatite B entre os 73 pacientes desta casuística. O autor destaca a importância de se pesquisar a hepatite B e outras DST em pessoas portadoras do VIH ou com SIDA, visando uma estratégia de profilaxia da hepatite B para estes pacientes, seja por uma educaçäo sanitária, seja por imunizaçäo ativa e passiva. Estudo da Hepatite B em portadores da SIDA.