Avaliação da recorrência da toxoplasmose ocular e fatores de risco associados em pacientes do Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - RJ

Made available in DSpace on 2018-03-07T14:28:02Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) ana_aleixo_ini_dout_2015.pdf: 1715189 bytes, checksum: 37aa6a5dd8ed3b128a86676e63910905 (MD5)Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.A Toxoplasmose ocular (TO) é principal causa de uveítes posteriores no Brasil e em diversas partes do mundo, porém apenas um baixo percentual dos pacientes infectados pelo T. gondii é que manifesta a doença ocular. Frequentemente o indivíduo acometido sofre recorrências durante a vida, sendo esse aspecto emblemático do quadro ocular, mas os fatores de risco e susceptibilidade do hospedeiro tanto para a ocorrência da retinocoroidite quanto para as suas recidivas ainda não foram bem estabelecidos. A idade do indivíduo no momento da infecção e nos episódios de reativação vem sendo considerados como fatores determinantes no risco de recidiva, que também poderia estar associado ao polimorfismo genético de citocinas como IFN-\03B3 que tem importante papel na imunidade contra patógenos intracelulares. O conhecimento do comportamento da doença e de fatores de risco pode trazer benefícios tanto no prognóstico quanto no manejo e acompanhamento dos indivíduos acometidos e também pode fornecer indícios para o esclarecimento da fisiopatogenia da doença. O presente estudo acompanhou 230 pacientes atendidos entre 2010 e 2015 no Laboratório de Oftalmologia Infecciosa do Instituto Nacional de Infectologia Evandro Chagas com toxoplasmose ocular ativa, avaliando a frequência da recorrência e sua correlação com gênero, idade, polimorfismo genético para IFN-\03B3 +874T/A e número de lesões retinocoroidianas no atendimento inicial. O acompanhamento envolveu 118 (51.30%) homens e 112 (48.70%) mulheres, com idades que variaram de 14 a 77 anos com mediana de 30.97 anos (DP=11.38) Observou-se 52 (22.61%) casos de lesões primárias e 178 (77.39%) casos com cicatrizes de retinocoroidite associadas a lesão ativa no início do estudo. Durante o acompanhamento foram verificados 162 episódios de recidiva em 104 (45.22%) pacientes. Em 40 (17.39%) indivíduos foi observada baixa de visão severa (20/200 ou pior) no olho acometido atribuível a toxoplasmose ocular, estando associada a localização da lesão de retinocoroidite em 27 (67.50%) pacientes. Na análise de sobrevida verificou-se que o risco de recorrência durante todo o acompanhamento foi 60% maior em pacientes com lesão primária (HR=1.60, 95% CI=1.07-2.40) pelo modelo de Prentice, Williams e Peterson (PWP), sendo influenciada pela idade (HR=1.03, 95% CI=1.01-1.04) e pelo genótipo AT do polimorfismo genético para IFN +874 (HR=1,49, 95% CI= 1.04- 2.14). Entretanto, a associação do polimorfismo genético para IFN +874 TA não foi confirmada quando excluídos os pacientes com lesão única que não recorreram, não podendo, portanto, ser confirmada pela metodologia utilizada. A toxoplasmose ocular tem altos índices de recidiva nos primeiros anos de acompanhamento após um episódio de atividade sendo a baixa de visão severa causada frequentemente pela localização central da lesão de retinocoroidite. É fundamental considerar a localização da lesão em estudos que analisem o prognóstico de visão como medida de efetividade de estratégias de tratamento e prevenção. O risco de recidivas de toxoplasmose ocular após um episódio ativo aumentou com a idade e foi substancialmente maior nos indivíduos com lesão primária, o que poderia sugerir que indivíduos com essa característica e mais idosos seriam beneficiados por estratégias de profilaxia de recorrências com antimicrobianosOcular Toxoplasmosis (OT) is a leading cause of posterior uveitis in Brazil and all over the world, but only a low percentage of patients infected with T. gondii manifests eye disease. Recurrence is a hallmark of ocular toxoplasmosis, but the risk factors and host susceptibility for both the occurrence and reactivation of retinochoroiditis have not been well established. The age of the individual at the time of infection and recurrent episodes has been considered as key factors in the risk of recurrence, which could also be associated with the genetic polymorphism of cytokines such as IFN-\03B3, which plays an important role in immunity against intracellular pathogens. Knowledge about the course of the disease and risk factors can bring benefits both in prognosis and in the management and monitoring of affected individuals and can also provide clues to clarify the pathogenesis of the disease. This study followed 230 patients followed between 2010 and 2015 at Infectious Ophthalmology Laboratory of the National Institute of Infectious Diseases Evandro Chagas with active ocular toxoplasmosis, evaluating the frequency of recurrence and its correlation with gender, age, genetic polymorphism of IFN -\03B3 + 874T / A and number of retinochoroidal scars in the first visit. The follow-up involved 118 (51.30%) men and 112 (48.70%) women, with ages ranging 14-77 years, median of 30.97 years (SD = 11.38). Fifty two (22.61%) patients with primary lesions and 178 (77.39%) cases of active retinochoroiditis with associated scars were found at the baseline visit. During follow-up 162 episodes of relapse were observed in 104 (45.22%) patients. Forty (17.39%) individuals exhibited severe vision loss (20/200 or worse) in the affected eye attributable to ocular toxoplasmosis and its main cause was the central location of the retinochoroidal scar in 27 (67.50%) patients The survival analysis showed that the risk of recurrence during the follow-up 60% higher in patients with primary lesion (HR=1.60, 95% CI=1.07-2.40) by Prentice, Williams and Peterson (PWP) modeling, influenced by age (HR = 1.03 95% CI = 1.01 to 1.04) and AT genotype of IFN-\03B3 +874T/A (HR=1,49, 95% CI= 1.04- 2.14). The association of recurrence and genetic polymorphism of IFN -\03B3 + 874T could not be confirmed when patients with primary retinochoroidal lesions and no recurrence were excluded, so could not be confirmed by the methodology used. Ocular toxoplasmosis has high recurrence rates in the early years of follow-up after an episode of activity and severe vision loss in often caused by is the central location of retinochoroiditis lesion. It is crucial to consider the location of the retinochoroidal scar in studies that uses visual outcome as a measure of effectiveness of treatment and prevention strategies. The risk of reactivation of OT after an acute episode increased with age and was significantly higher in individuals with primary lesion, which could suggest that these individuals would benefit by recurrence prevention strategies with antimicrobial drug

Toxoplasmic Retinochoroiditis: Clinical Characteristics and Visual Outcome in a Prospective Study

Submitted by Sandra Infurna ([email protected]) on 2017-01-03T10:42:23Z No. of bitstreams: 1 maria_amendoeira_etal_IOC_2016.pdf: 2854505 bytes, checksum: 375146a4a7d42c039630914e9afa7f7c (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-01-03T10:52:40Z (GMT) No. of bitstreams: 1 maria_amendoeira_etal_IOC_2016.pdf: 2854505 bytes, checksum: 375146a4a7d42c039630914e9afa7f7c (MD5)Made available in DSpace on 2017-01-03T10:52:40Z (GMT). No. of bitstreams: 1 maria_amendoeira_etal_IOC_2016.pdf: 2854505 bytes, checksum: 375146a4a7d42c039630914e9afa7f7c (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Oftalmologia Infecciosa,. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Oftalmologia Infecciosa,. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Oftalmologia Infecciosa,. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose. Rio de Janeiro, RJ. Brasil.Purpose To ascertain the clinical features and visual outcome of toxoplasma retinochoroiditis in a large series of cases. Subjects and Methods Two hundred and thirty subjects diagnosed with active toxoplasma retinochoroiditis were prospectively followed for periods ranging from 269 to 1976 days. All patients presented with active retinochoroiditis and positive IgG T. gondii serology at the beginning of the study and received a standardized drug treatment for toxoplasmosis, both in the first episode and in the subsequent recurrences. Results The group involved 118 (51.3%) men and 112 (48.7%) women, with ages ranging from 14 to 77 years, mean of 32.4 years (SD = 11.38). Primary retinochoroidal lesions were observed in 52 (22.6%) cases and active retinochoroiditis combined with old scars in 178 (77.4%) subjects at the beginning of the study. A hundred sixty-two recurrent episodes in 104 (45.2%) patients were observed during follow-up. New subclinical retinochoroidal lesions were detected in 23 of 162 (14.2%) recurrences episodes during the follow-up. Posterior segment complications were observed in 73 (31.7%) subjects. Retinochoroidal lesions adjacent to the optic nerve and in the macular area were observed in 27 of 40 (67.5%) cases of severe visual impairment (VA = 20/200 or worse). Conclusion Toxoplasma retinochoroiditis in this population had a high recurrence rate after an active episode. Severe visual impairment was associated with location of the retinochoroidal scar, recurrences and posterior segment complications. It is crucial to consider the location of the lesion in studies analyzing visual prognosis as a measure for treatment effectiveness and prevention strategies

Levantamento soroepidemiológico da frequência de Toxoplasma gondii em doadores de córnea do Banco de Olhos de Volta Redonda, RJ, Brasil]

Toxoplasma gondii é um parasito protozoário que infecta até um terço da população mundial. A infecção é adquirida principalmente pela ingestão de alimentos ou água que é contaminada com oocistos eliminados por gatos infectados ou por comer carne crua ou mal cozida contendo cistos de tecido e por transfusão de sangue ou transplante de órgãos. O diagnóstico de toxoplasmose pode ser estabelecido pela detecção direta do parasito ou por técnicas sorológicas. O objetivo do presente estudo foi verificar a soroprevalência da toxoplasmose em doadores de córnea do Rio de Janeiro, através de material obtido do Banco de Olhos de Volta Redonda, RJ, Brasil. Os anticorpos IgM e IgG anti-T. gondii foram investigados em 426 soros de dadores de córnea, utilizando o teste de anticorpos fluorescentes indiretos (IFAT) e técnicas de ensaio imunoenzimático (ELISA). Os participantes foram selecionados por amostragem de conveniência. As informações demográficas dos sujeitos do estudo, incluindo seu sexo, idade, causa de morte e região de origem, foram registradas. Das 426 amostras de soro, 338 (79,34%) e 17 (3,99%) foram positivas em relação ao anti-T. gondii IgG e IgM ELISA e/ou IFAT, respectivamente. Esses dados demonstram a importância dos inquéritos soroepidemiológicos regionais e nacionais para definir estratégias de saúde pública que possam reverter e reduzir a prevalência de toxoplasmose sorológica no Brasil

Retinography of a subject with focal exudative retinochoroiditis associated with a pigmented scar.

<p>Credits: ALQCA.</p

Comparison of immunological and molecular methods for laboratory diagnosis of ocular toxoplasmosis in blood, serum and tears in Brazil.

Ocular toxoplasmosis (OT) is caused by protozoan T. gondii. Ophthalmological examination is considered the gold standard for OT diagnosis, and laboratory tests are used for diagnostic confirmation. However, these tests can present different results, which change depending on their basis, on sample type and on patients' clinical alteration. Thus, the aim of the present study is to assess immunodiagnostic and molecular techniques applied in blood, serum and tear fluid to diagnose T. gondii infection in patients seen at an Ophthalmology Clinic. In total, 160 patients were included in the study, 40 of them had OT with active lesions (G1); 40 had OT with healed lesions (G2), 40 had non-toxoplasmic uveitis (G3) and 40 had no ocular alterations (G4). Serum samples were subjected to Immunoenzymatic Assay (ELISA) and to Indirect Immunofluorescence Reaction (IFAT) to search for anti-T. gondii IgM and IgG. Tear fluid samples were analyzed through ELISA for IgA research. All blood and tear fluid samples were subjected to conventional polymerase chain reaction (cPCR) and in a Nested PCR model for T. gondii DNA amplification with targets B1, GRA7 and REP 529. IgG and IgM anti-T. gondii was detected in serum samples from 106 and 15 patients, respectively, when combining ELISA and IFAT results. Anti-T.gondii IgA antibodies were detected in 9.2% of the tear material. Nested PCR with GRA7 target showed higher positivity in blood samples (24.4%); Nested PCR with B1 target showed a higher frequency of positivity in tears (15%). Biological samples of patients with active lesions showed the highest positivity frequencies in all immunodiagnostic assays, as well as in most PCR models. The present results highlighted the need of associating techniques with different fundamentals to confirm OT diagnosis. Furthermore, further tear fluid analyses should be performed to validate this biological material as lesser invasive alternative for the more accurate OT diagnosis

Factors related do severe vision loss in 230 subjects with ocular toxoplasmosis (univariate analysis).

<p>Factors related do severe vision loss in 230 subjects with ocular toxoplasmosis (univariate analysis).</p

Complications of posterior segment attributable to toxoplasma retinochoroiditis in 73 of 230 subjects followed at the INI.

<p>Complications of posterior segment attributable to toxoplasma retinochoroiditis in 73 of 230 subjects followed at the INI.</p

Age distribution of 230 subjects with toxoplasma retinochoroiditis observed at INI.

<p>Age distribution of 230 subjects with toxoplasma retinochoroiditis observed at INI.</p

Retinography of the same subject of Fig 2 after standardized drug scheme for toxoplasmosis, showing healed lesions (scars).

<p>Credits: ALQCA.</p

Flow diagram of subjects follow-up.

<p>Data analysis employed summary measures such as means and medians of quantitative variables and percentages for qualitative variables. To investigate the association between severe vision impairment and posterior segment complications, age, location of retinochoroidal lesion and recurrence during follow-up, the chi-square test was used and P-values <0.05 were considered significant.</p