João Furtado

Causes of Blindness and Visual Impairment in Latin America

We review what is known in each country of the Latin American region with regards to blindness and visual impairment and make some comparisons to Hispanic populations in the United States. Prevalence of blindness varied from 1.1% in Argentina to 4.1% in Guatemala in people 50 years of age and older, with the major cause being cataract. Diabetic retinopathy and glaucoma are starting to make serious inroads, although epidemiological data are limited, and age-related macular degeneration is now a concern in some populations. Infectious diseases such as trachoma and onchocerciasis are quickly diminishing. Although progress has been made, retinopathy of prematurity remains the major cause of childhood blindness. If VISION 2020 is to succeed, many more epidemiological studies will be needed to set priorities, although some can be of the Rapid Assessment of Avoidable Blindness design. Developing the infrastructure for screening and treatment of ophthalmic disease in Latin America continues to be a challenge.

Toxoplasmosis: A global threat

Toxoplasmosis, a disease described worldwide, which is caused by the protozoan Toxoplasma gondii, commonly involves the retina. The disease has a higher impact in immunocompromised individuals and in congenital infection because of the severity of central nervous system involvement. Although simple prophylactic measures could reduce transmission, T. gondii seroprevalence is still high, especially in South America. Educational campaigns and the development of new drugs to prevent primary infection could potentially reduce the burden of the disease.

Política industrial e desenvolvimento

Este artigo examina alguns enfoques teoricos de suporte a politicaindustrial, com enfase na perspectiva neoschumpeteriano/evolucionario.Aplica esta perspectiva para analisar algumas experiencias bem sucedidasde politica industrial e desenvolvimento economico no Brasil ate fins dosanos 1970, bem como as tentativas fracassadas de implementar taispoliticas a partir dos anos 1980. Por ultimo avalia a politica industrial dogoverno 2003-2006, e argumenta que, apesar de alguns aspectos positivos-foco na inovacao, metas claramente definidas e uma nova organizacaoinstitucional-, essa politica apresenta fraquezas, como a incompatibilidadecom a politica macroeconomica, inconsistencias entre instrumentoseconomicos, deficiencias em infraestrutura e no sistema de ciencia,tecnologia e inovacao, e falta de coordenacao e decisao politica.

Ocular toxoplasmosis II: clinical features, pathology and management

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.

Ocular toxoplasmosis I: parasitology, epidemiology and public health

Ocular toxoplasmosis results from retinal infection with the protozoan, Toxoplasma gondii. This parasite, which exists as multiple clonal subpopulations and in three stages, is capable of replication in any nucleated cell of its primary feline or multiple paratenic hosts. Human seroprevalence of toxoplasmosis is high across the globe, but with geographic variation. While prevalence of ocular toxoplasmosis is not well documented, toxoplasmic retinochoroiditis is the commonest form of posterior uveitis in many countries. Correlation of parasite genotype with disease is an important area of new research. Ocular infection with T. gondii often follows ingestion of bradyzoites in undercooked infected meat. Oocysts may survive for an extended period in the environment, and water contaminated with oocysts is an important source in toxoplasmosis epidemics. Ocular toxoplasmosis is preventable by a combination of community activities and personal measures. Public health action is well justified by the considerable burden of congenital and postnatal infections.

Toxoplasma gondii Tachyzoites Cross Retinal Endothelium Assisted by Intercellular Adhesion Molecule-1 In Vitro

Retinal infection is the most common clinical manifestation of toxoplasmosis. The route by which circulating Toxoplasma gondii tachyzoites cross the vascular endothelium to enter the human retina is unknown. Convincing studies using murine encephalitis models have strongly implicated leukocyte taxis as one pathway used by the parasite to access target organs. To establish whether tachyzoites might also interact directly with vascular endothelium, we populated a transwell system with human ocular endothelial cells. Human retinal endothelial monolayers permitted transmigration of tachyzoites of RH and three natural isolate strains. Antibody blockade of intercellular adhesion molecule‐1 significantly reduced this migration, but did not impact tachyzoite movement across an endothelial monolayer derived from the choroid, which lies adjacent to the retina within the eye. In demonstrating that tachyzoites are capable of independent migration across human vascular endothelium in vitro, this study carries implications for the development of therapeutics aimed at preventing access of T. gondii to the retina.

Migration of Toxoplasma gondii–Infected Dendritic Cells across Human Retinal Vascular Endothelium

PURPOSE Toxoplasma gondii, the parasite responsible for ocular toxoplasmosis, accesses the retina from the bloodstream. We investigated the dendritic cell as a potential taxi for T. gondii tachyzoites moving across the human retinal endothelium, and examined the participation of adhesion molecules and chemokines in this process. METHODS CD14-positive monocytes were isolated from human peripheral blood by antibody-mediated cell enrichment, and cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to generate dendritic cells. Transmigration assays were performed over 18 hours in transwells seeded with human retinal endothelial cells and using dendritic cells exposed to laboratory or natural strains of T. gondii tachyzoites. Parasites were tagged with yellow fluorescent protein to verify infection. In some experiments, endothelial monolayers were preincubated with antibody directed against adhesion molecules, or chemokine was added to lower chambers of transwells. RESULTS Human monocyte-derived dendritic cell preparations infected with laboratory or natural strain T. gondii tachyzoites transmigrated in larger numbers across simulated human retinal endothelium than uninfected dendritic cells (P ≤ 0.0004 in 5 of 6 experiments). Antibody blockade of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and activated leukocyte cell adhesion molecule (ALCAM) inhibited transmigration (P ≤ 0.007), and CCL21 or CXCL10 increased transmigration (P ≤ 0.031). CONCLUSIONS Transmigration of human dendritic cells across retinal endothelium is increased following infection with T. gondii. Movement may be impacted by locally produced chemokines and is mediated in part by ICAM-1, VCAM-1, and ALCAM. These findings have implications for development of novel therapeutics aimed at preventing retinal infection by T. gondii.

Immunohistochemical expression of HLA-DR in the conjunctiva of patients under topical prostaglandin analogs treatment.

PurposeSubclinical inflammation may be observed in patients using topical antiglaucomatous drugs. The objective of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of an immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. Subjects and MethodsThirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides, and prepared for immunohistochemical analysis. ResultsBefore the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression of HLA-DR in the conjunctiva (mild). After 1 month on prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was found (P=0.27). ConclusionsThe use of prostaglandin analogs eye drops provokes a subclinical inflammatory reaction, observed by HLA-DR expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

River blindness: An old disease on the brink of elimination and control

For decades, onchocerciasis (or river blindness) was one of the most common infectious causes of blindness in the world. Primarily an infection of Africa, with limited distribution in the new world, disease due to the nematode Onchocerca volvulus is rapidly diminishing as a result of large public health campaigns targeting at risk populations in Africa and the Americas. Existing and newly-developed treatment strategies offer the chance to eliminate onchocercal ocular morbidity in some parts of the world. This article reviews these treatment strategies, current clinical and epidemiologic aspects of onchocerciasis, and the next steps toward elimination.

Toxoplasma gondii migration within and infection of human retina.

Toxoplasmic retinochoroiditis is a common blinding retinal infection caused by the parasite, Toxoplasma gondii. Basic processes relating to establishment of infection in the human eye by T. gondii tachyzoites have not been investigated. To evaluate the ability of tachyzoites to navigate the human retina, we developed an ex vivo assay, in which a suspension containing 1.5×107 parasites replaced vitreous in a posterior eyecup. After 8 hours, the retina was formalin-fixed and paraffin-embedded, and sections were immunostained to identify tachyzoites. To determine the preference of tachyzoites for human retinal neuronal versus glial populations, we infected dissociated retinal cultures, subsequently characterized by neuron-specific enolase or glial fibrillary acidic protein expression, and retinal cell lines, with YFP-expressing tachyzoites. In migration assays, retinas contained 110–250 live tachyzoites; 64.5–95.2% (mean  = 79.6%) were localized to the nerve fiber layer, but some were detected in the outer retina. Epifluorescence imaging of dissociated retinal cultures 24 hours after infection indicated preferential infection of glia. This observation was confirmed in growth assays, with significantly higher (p≤0.005) numbers of tachyzoites measured in glial verus neuronal cell lines. Our translational studies indicate that, after entering retina, tachyzoites may navigate multiple tissue layers. Tachyzoites preferentially infect glial cells, which exist throughout the retina. These properties may contribute to the success of T. gondii as a human pathogen.