Dry eye disease caused by viral infection: review

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

Experimental infection of dogs with a Brazilian strain of Rickettsia rickettsii: clinical and laboratory findings

The bacterium Rickettsia rickettsii is the etiological agent of an acute, severe disease called Rocky Mountain spotted fever in the United States or Brazilian spotted fever (BSF) in Brazil. In addition to these two countries, the disease has also been reported to affect humans in Mexico, Costa Rica, Panama, Colombia and Argentina. Like humans, dogs are also susceptible to R. rickettsii infection. However, despite the wide distribution of R. rickettsii in the Western Hemisphere, reports of R. rickettsii-induced illness in dogs has been restricted to the United States. The present study evaluated the pathogenicity for dogs of a South American strain of R. rickettsii. Three groups of dogs were evaluated: group 1 (G1) was inoculated ip with R. rickettsii; group 2 (G2) was infested by R. rickettsii-infected ticks; and the control group (G3) was infested by uninfected ticks. During the study, no clinical abnormalities, Rickettsia DNA or R. rickettsii-reactive antibodies were detected in G3. In contrast, all G1 and G2 dogs developed signs of rickettsial infection, i.e., fever, lethargy, anorexia, ocular lesions, thrombocytopenia, anemia and detectable levels of Rickettsia DNA and R. rickettsii-reactive antibodies in their blood. Rickettsemia started 3-8 days after inoculation or tick infestation and lasted for 3-13 days. Our results indicate that a Brazilian strain of R. rickettsii is pathogenic for dogs, suggesting that canine clinical illness due to R. rickettsii has been unreported in Brazil and possibly in the other South American countries where BSF has been reported among humans.

Avaliação da reatividade de anticorpos anti-Toxoplasma gondii pela técnica de citometria de fluxo como indicadores de lesão ocular em soros de recém-nascidos com toxoplasmose congênita

A retinocoroidite é a manifestação mais comum causada pela infecção congênita por Toxoplasma gondii. Devido a gravidade das lesões oculares que podem até levar à perda completa da visão, a detecção precoce da toxoplasmose congênita e da lesão ocular são essenciais para o tratamento. Este trabalho possuiu o objetivo de avaliar a aplicabilidade da pesquisa de anticorpos IgG e das subclasses IgG1, IgG2, IgG3 e IgG4 anti-T. gondii por citometria de fluxo como marcador laboratorial das diferentes formas de lesões retinocoroidais na toxoplasmose congênita. Foram analisadas 88 amostras de soro de recém-nascidos com toxoplasmose congênita, sendo 25 sem lesão ocular (SL), 10 com lesão ocular ativa (RA), 26 com lesão ocular ativa e cicatricial (RAC) e 27 com lesão ocular cicatricial (RC). Foram também utilizadas 19 amostras de soro de recém-nascidos não infectados que apresentaram IgG positivo após o nascimento (NI). Essas amostras foram obtidas a partir de soros de recémnascidos participantes de um programa de triagem neonatal realizado em Minas Gerais realizado nos anos de 2006 e 2007. Os resultados demonstraram que os recém-nascidos com toxoplasmose congênita apresentam maior reatividade de anticorpos IgG total e subclasses IgG1, IgG2 e IgG3 do que indivíduos não infectados. No grupo não infectado, o único anticorpo com mais de 50% de indivíduos com alta reatividade de anticorpos foi IgG4. Ao comparar os grupos de indivíduos com toxoplasmose congênita, foi observado que o grupo RAC, seguido de RC, apresentou maior reatividade principalmente para os anticorpos IgG1 e IgG3 comparado aos recém-nascidos dos grupos RA e SL, enquanto que pacientes do grupo RA apresentaram maior reatividade para IgG4 do que indivíduos dos outros grupos. IgG1 foi a única subclasse capaz de diferenciar os grupos NI, SL dos grupos RAC e RC. Também foi avaliado o índice de avidez de IgG total, que não permitiu estabelecer nenhum critério de diferenciação das formas de lesão ocular causadas pelo T. gondii. Portanto, a citometria de fluxo demonstrou que pode ser um método laboratorial complementar para ser utilizado como indicador das diferentes lesões oculares causadas pela toxoplasmose congênita.

Evaluation of polymethylmethacrylate as ocular implant in rabbits subjected to evisceration

Spheres of different types of material are used for the replacement of lost volume after removal of the eye bulb or its content to prevent contraction of the orbital cavity. The aim of this study was to evaluate the scope of polymethylmethacrylate (PMMA) used as intraocular implant in eviscerated rabbit eye. Twelve New Zealand rabbits underwent unilateral evisceration of the left eye, with subsequent implantation of PMMA sphere 12 mm in diameter. Clinical evaluation was performed daily during the first 15 days after surgery and every 15 days until the end of the study period (180 days). For the histopathological analysis, three animals per trial underwent enucleation at 15, 45, 90 and 180 days after evisceration. There was no wound dehiscence, signs of infection or implant extrusion in any animal throughout the study period. Histological examination revealed the formation of fibrovascular tissue around the implants. The PMMA behaved as inert and non-integrable.

Clinical and serological evidence of Toxocara infection in school children from Morrope District, Lambayeque, Peru

The aim of this study was to estimate the frequency of human toxocariosis in a child population from Morrope district, Lambayeque, Peru. From October to December 2005, 182 school children (96 male and 86 female) were studied. Blood samples were collected for Toxocara ELISA-IgG test and hematological examination. Additionally, stool samples were collected for coproparasitological examination to check cross reactions. We found frequency of positives in 32.4% (59/182) with a significant higher proportion of positivity in male children (p < 0.00001). 71.2% of the children with positive serology (52 male and seven female), were between five and 10 years old, 77.96% had respiratory symptoms, 61.02% had ocular manifestations, 38.98% had hepatic symptoms, 38.98% had mild or moderate eosinophilia, signs statistically associated with seropositivity. 83.5% of studied population had some intestinal parasite, such as: Blastocystis hominis (53.3%), Giardia lamblia (31.3%), Entamoeba coli (29.1%), Entamoeba histolytica/E. dispar (1.1%), Hymenolepis nana (5.49%), and Ascaris lumbricoides (3.3%), but they had not any association with serology results. The ownership of dogs or/and cats were significantly associated with seropositivity to anti-Toxocara antibodies although the presence of such pets within the house was not. In conclusion, clinical and serological evidence of Toxocara infection exists in the studied population.

Ocular Toxoplasmosis Reactivation During Pregnancy – A Case Report

Introduction: Toxoplasmosis is caused by Toxoplasma gondii and may be acquired from food or water contaminated with cat feces or by vertical transmission. Severe fetal complications can overcome during pregnancy. There are also rare case-reports of congenital toxoplasmosis from previously immunized pregnant women; usually these women being had prior retinal toxoplasmic lesions. Immunosuppresion is one of the risk factors which accounts for some of these cases. Case report: 30 year-old pregnant woman, OI 2002, brazilian, previously healthy, admitted in Ophtalmology Department because of sudden left eye amaurosis in June, 2010. The fundoscopy revealed retinal scars suggesting previous infections; she was treated with corticoids and spiramycin for ocular toxoplasmosis reactivation. Previous serum analysis (2008) showed immunity to T. Gondii, but in July the IgM was negative and high levels of specific IgG were found (1227UI/mL). The serologic findings were later confirmed by a more accurate laboratory technique which found the IgM to be also positive. An amniocentesis was performed and it was negative for fetal transmission. Clinical and ultrasound follow-up throughout the rest of the gestational period was normal; daily spiramycin intake was maintained. An uneventful term delivery was performed. Neither the newborn’s serum analysis nor the histopathological study of the placenta were positive for congenital infection. Conclusion: Toxoplasmosis reactivation in pregnant women without immunosuppression is rare but is more likely to occur if previous post-infectious retinal scars are present. T. gondii infection is endemic in Brazil, so the geographical origin is important. If risk factors are present, fundoscopy should be performed every three months during pregnancy and one should always be aware of any visual symptoms. If you suspect reactivation, start medical prophylaxis for fetal transmission, perform amniocentesis and regular ultrasound follow-up.

Ocular lesions in gerbils (Meriones unguiculatus) infected with low larval burden of Toxocara canis: observations using indirect binocular ophthalmoscopy

To study the frequency of ocular lesions in 30 gerbils infected with 100 embryonated eggs of Toxocara canis, indirect binocular ophthalmoscopy was performed 3, 10, 17, 24, 31 and 38 days after infection. All the animals presented larvae in the tissues and 80% presented ocular lesions. Hemorrhagic foci in the choroid and retina were present in 92% of the animals with ocular lesions. Retinal exudative lesions, vitreous lesions, vasculitis and retinal detachment were less frequent. Mobile larvae or larval tracks were observed in four (13.3%) animals. Histological examination confirmed the ophthalmoscopic observations, showing that the lesions were focal and sparse. In one animal, there was a larva in the retina, without inflammatory reaction around it. The results demonstrated that gerbils presented frequent ocular lesions after infection with Toxocara canis, even when infected with a small number of embryonated eggs. The lesions observed were focal, consisting mainly of hemorrhages with signs of reabsorption or inflammation in different segments of eye, and differing from the granulomatous lesions described in ocular larva migrans in humans.

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in Colombian patients with acute and chronic ocular toxoplasmosis

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35%) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10%). In group 2 (recurrences) in 1/7 (14%) we found IgM and IgA test positives and in 1/7 (14%) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18%). These results show that serum IgM or IgA or IgE can be present during recurrences.

Concurrent cutaneous, visceral and ocular leishmaniasis caused by Leishmania (Viannia) braziliensis in a kidney transplant patient

Although cases of leishmaniasis co-infection have been described in acquired immunodeficiency syndrome patients as well as those who have undergone organ transplants, to our knowledge, the present report is the first documented case of simultaneous cutaneous, visceral and ocular leishmaniasis due to Leishmania (Viannia) braziliensis in a transplant patient. The patient had been using immunosuppressive drugs since receiving a transplanted kidney. The first clinical signs of leishmaniasis included fever, thoracic pain, hepatosplenomegaly, leucopenia and anemia. The cutaneous disease was revealed by the presence of amastigotes in the skin biopsy. After three months, the patient presented fever with conjunctive hyperemia, intense ocular pain and low visual acuity. Parasites isolated from iliac crest, aqueous humor and vitreous body were examined using a range of molecular techniques. The same strain of L. (V.) braziliensis was responsible for the different clinical manifestations. The immunosuppressive drugs probably contributed to the dissemination of Leishmania.

Experimental infection of dogs with a Brazilian strain of Rickettsia rickettsii: clinical and laboratory findings

The bacterium Rickettsia rickettsii is the etiological agent of an acute, severe disease called Rocky Mountain spotted fever in the United States or Brazilian spotted fever (BSF) in Brazil. In addition to these two countries, the disease has also been reported to affect humans in Mexico, Costa Rica, Panama, Colombia and Argentina. Like humans, dogs are also susceptible to R. rickettsii infection. However, despite the wide distribution of R. rickettsii in the Western Hemisphere, reports of R. rickettsii-induced illness in dogs has been restricted to the United States. The present study evaluated the pathogenicity for dogs of a South American strain of R. rickettsii. Three groups of dogs were evaluated: group 1 (G1) was inoculated ip with R. rickettsii; group 2 (G2) was infested by R. rickettsii-infected ticks; and the control group (G3) was infested by uninfected ticks. During the study, no clinical abnormalities, Rickettsia DNA or R. rickettsii-reactive antibodies were detected in G3. In contrast, all G1 and G2 dogs developed signs of rickettsial infection, i.e., fever, lethargy, anorexia, ocular lesions, thrombocytopenia, anemia and detectable levels of Rickettsia DNA and R. rickettsii-reactive antibodies in their blood. Rickettsemia started 3-8 days after inoculation or tick infestation and lasted for 3-13 days. Our results indicate that a Brazilian strain of R. rickettsii is pathogenic for dogs, suggesting that canine clinical illness due to R. rickettsii has been unreported in Brazil and possibly in the other South American countries where BSF has been reported among humans.

Ocular toxoplasmosis: the influence of patient age

The influence of patient age on various features of ocular toxoplasmosis has been a subject of study for many years. The age at which Toxoplasma gondii infection occurs in different populations is related to socioeconomic factors and studies suggest that ocular toxoplasmosis is a more severe disease at the extremes of age. The prevalence of ocular involvement is markedly different between individuals with congenital and those with post-natally acquired infections. Even among those with post-natally acquired infections, age influences the risk and timing of ocular involvement. The severity of toxoplasmic retinochoroiditis (in terms of lesion size, location and associated inflammation) is also affected by patient age at the time of initial infection or recurrence. The risk of recurrent toxoplasmic retinochoroiditis is influenced by age at the time of initial infection and age at most recent episode of active disease. Understanding of relationships between ocular toxoplasmosis and patient age is incomplete; evidence has often been indirect and in some cases conflicting. The influence of patient age on ocular toxoplasmosis should be studied in a systematic manner to provide a better understanding of disease mechanisms and to provide clinical information that can used to establish better strategies for disease treatment and prevention.

Contributions to the history of ocular toxoplasmosis in Southern Brazil

The evolution of knowledge regarding ocular toxoplasmosis over the last 30 years is described based on studies and observations performed in Southern Brazil. The isolation ofToxoplasma gondii established the definitive diagnosis of the disease. It was proven that in most cases, the disease was acquired after birth, a concept supported by the description of numerous familial cases and observation of the disease many years after primary infection. Epidemiological studies showed important regional variations in the prevalence of the disease due to different factors, including the types of strains involved, of which type I predominates. The large number of patients also enabled detailed study of the different forms of clinical presentation of the disease and its complications. New parameters have been established for the use of steroids and the management of pregnant women with active lesions. Studies on the epidemiology of toxoplasmic infection in pregnant women and newborns showed a high prevalence of infection. The different factors of exposure to infection have also been studied. Gradually, preventive actions have been developed in the sphere of public health, although they have not been sufficiently effective. Trends for future research over the next few years are also outlined.

Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.

Ocular toxoplasmosis: evaluation of lacrimal - specific secretory IgA levels in both patients with active and inactive phases of the disease

Ocular toxoplasmosis can result in recurrent uveitis. Studies have shown that a correlation between active ocular toxoplasmosis and the presence of anti-Toxoplasma gondii secretory IgA (SIgA) in tears. This study compares anti-T. gondii SIgA levels in patients' tears during the acute and inactive phases of toxoplasmic uveitis. Twenty-nine positive tear specific SIgA for T. gondii patients with acute toxoplasmic uveitis were selected and were followed-up for at least two years, when the anti-T. gondii SIgA tears levels were determined. Specific SIgA for T. gondii was negative in 22 patients (75.86%) and positive in seven patients (24.13%) of whom six (85.7%) were followed over three years. Average SIgA levels during the acute phase are 1.54 and decrease significantly to 0.72 (p = 0.0001) during the inactive phase of disease. Because anti-T. gondii SIgA in the tear is negative in 75.86% of patients after the acute phase of infection, T. gondii SIgA levels may be used as a complementary diagnostic marker for active ocular toxoplasmosis.

Single nucleotide polymorphisms in the interferon gamma gene are associated with distinct types of retinochoroidal scar lesions presumably caused by Toxoplasma gondii infection

The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ gene ( IFNG ) with different types of retinal scar lesions presumably caused by toxoplasmosis were investigated in a cross-sectional population-based genetic study. Ten SNPs were investigated and after Bonferroni correction, only the associations between SNPs rs2069718 and rs3181035 with retinal/retinochoroidal scar lesions type A (most severe scar lesions) and C (least severe scar lesions), respectively, remained significant. The associations of two different IFNG SNPs with two different types of retinal lesions attributable to toxoplasmosis support the hypothesis that different inflammatory mechanisms underlie the development of these lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear cells stimulated with Toxoplasma gondii antigens was also investigated. The association between SNP rs2069718 and type A scar lesions revealed that differential IFN-γ levels are correlated with distinct genotypes. However, no correlation was observed with IFN-γ secretion levels and the SNP rs3181035 , which was significantly associated with type C scar lesions. Our findings strongly suggest that immunogenetic studies of individuals with congenital or postnatally acquired infection are needed to better understand the role of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis.