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Use of levamisole in parasitic infections.

Levamisole is a drug of choice for treatment of ascariasis. With recommended dosages, it is virtually free of side effects. Single doses of 50 to 150mg will eliminate all parasites in 90 to 100% of ascariasis patients irrespective of worm burden. Activity against hookworms has been demonstrated for levamisole but the most effective treatment regimen has not been determined. Further drug trials are needed for better assessment of efficacy. Levamisole has little or no curative action on infections with whipworms and pinworms. It may have some activity against strongyloides but confirmatory studies are needed. It has been shown that levamisole has significant activity against microfilariae of Wuchereria bancrofti and Brugia malayi. It is not, however, as effective as diethylcarbamazine ('Hetrazan'), and side reactions are greater. In tolerated doses, levamisole does not have significant action on adult forms or microfilariae of Onchoceea volvulus. The drug applied topically, however, may find a place in treatment of ocular onchocerciasis. Limited trials with levamisole for toxoplasmosis and chronic cutaneous leishmaniasis have given promising results, and further studies are indicated.

Ascariasis↗

AIDS and the eye. A 10-year experience.

BACKGROUND: The AIDS database at Fairfield Hospital, Melbourne, maintains information on eye pathology as identified by the three visiting ophthalmologists. Patients underwent an eye consultation: if they had ocular symptoms; if signs were seen on direct ophthalmoscopy by physicians; or when their CD4+ve cell count fell below 50/microL. The first AIDS-associated eye signs were identified in mid-1984. In the subsequent decade, 3257 patients in Victoria tested positive for HIV, and 845 of the 1123 who developed AIDS were treated at Fairfield Hospital. METHODS: We undertook a retrospective review of the Fairfield Hospital database to identify the AIDS-associated ocular problems seen. RESULTS: Some 723 patients had an eye consultation. In the earliest stage of HIV infection, minor non-specific ophthalmic involvement may occur. As the disease progresses, microvasculopathy (cottonwool spots and haemorrhages) appears. External disease also occurs such as molluscum contagiosum and Kaposi's sarcoma of the conjunctiva. With more suppression of the immune system, opportunistic infections become common, and have a considerable visual morbidity. Cerebral toxoplasmosis (117 patients) is only rarely associated with ocular involvement (three patients), but cytomegalovirus (CMV) commonly causes retinitis [204 patients (24%)]. It has been the AIDS-defining illness in 26 patients. A majority had the disease confined to one eye. Mean CD4 cell count at onset is 15 +/- 5 microL and it has been associated with a viraemia in all but two patients. Late complications of CMV retinitis include relapse in 41 (20%), spread to the other eye in 24 (12%), and retinal detachment in 30 (15%). Visual impairment follows from retinal destruction, optic nerve involvement, and retinal detachment. CONCLUSION: The ophthalmic workload from late ocular complications of AIDS is increasing. Newer and more effective methods of treatment are being developed. Ophthalmologists are becoming more aware of the need for universal precautions to avoid risks from this and other blood-borne infections.

AIDS-Related Opportunistic Infections↗

[Parinaud syndrome and Collier signal. Initial neurological manifestation in an HIV-1 positive patient].

We describe the third case in the literature of Parinaud's syndrome as the sole manifestation of brainstem toxoplasmosis, in a positive HIV-1 patient and review the literature concerning the possible etiologies of Parinaud's syndrome, enforcing that it is a rare manifestation of central nervous system toxoplasmosis. We refer to its occurrence without simultaneous obstructive hydrocephalus and increased intracranial pressure, pointing out the Collier signal which is not very well known, but has great semiotic value once it locates the lesion in the brainstem.

AIDS-Related Opportunistic Infections↗

Neuro-ophthalmological disorders in HIV infected subjects with neurological manifestations.

AIMS: To determine the frequency and features of neuro-ophthalmological manifestations in neurologically symptomatic HIV infected patients and to assess whether or not the visual evoked potential (VEP) features in these patients differ from those of neurologically asymptomatic HIV infected patients. METHODS: Neuro-ophthalmological evaluation was performed in 166 neurologically symptomatic confirmed HIV positive patients, of whom 75 with normal ophthalmological examination were further studied by means of VEPs. The VEPs values were compared to those obtained from 53 other confirmed HIV positive subjects with neither ophthalmological nor neurological manifestations, who served as a comparison group and to the references values of our laboratory. RESULTS: An abnormal neuro-ophthalmological examination was noted in 99/166 patients (60%). Eye movement disorders were present in 99 patients (51%). Visual field defects were detected in 39% of the patients. Optic neuropathy was noted in 31%, papilloedema in 27% and ocular motor nerve palsies in 26% of the patients. Toxoplasmosis and cryptococcosis were the most frequent associated pathologies, though in some patients the HIV itself was the presumed cause. VEPs were abnormal in 57% and 42% of patients with and without neurological manifestations, respectively. Compared to asymptomatic patients, symptomatic patients had a significantly increased mean latency; however, both groups had significant increase in mean latency compared to reference values. CONCLUSION: Neuro-ophthalmological manifestations are common in neurologically symptomatic HIV infected patients. Subclinical dysfunction in the visual pathways is a common phenomenon in both HIV infected patients with and without neurological symptoms, but neurologically symptomatic patients seem to have more damage in their visual pathways.

Adult↗

Screening for congenital toxoplasmosis in Brazil.

Toxoplasmosis acquired at the end of the pregnancy can produce ocular and neurological sequelae. The detection of IgM anti-Toxoplasma gondii in dried blood spots of newborns is an important tool for early treatment and prevention. In this study we showed results of a pilot study about the prevalence of congenital toxoplasmosis in Brazil and concluded that this disease should be included in the menu of neonatal screening programs.

Animals↗

Cytokine regulation of immunopathology in toxoplasmosis.

Toxoplasma gondii infection is an important cause of central nervous system and ocular disease, both in immunocompromised and in certain immunocompetent populations. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immuno-sufficient individuals. In this review, we have critically evaluated the body of experimental evidence indicating a role of CD4 T cells in systemic and local immunopathology associated with T. gondii infection. We also discuss the pathogenic roles of cytokines produced by T helper (Th) 1 and Th17 cells and the protective and homeostatic roles of interleukin (IL)-10, transforming growth factor-beta and IL-27 in modulating hypersensitivity responses induced by T. gondii.

Animals↗

[Uveitis in children: about 20 cases].

INTRODUCTION: Uveitis in children is rare: 3%-8% of all cases. It requires the same diagnostic and etiological processes as uveitis in adults, with additional difficulties at examination and a sometimes insidious progression. MATERIAL AND METHODS: Retrospective study of 20 cases of childhood uveitis from 1995 to 2000. All patients received an ophthalmologic examination and an etiological search, with specific and/or symptomatic treatment and follow-up lasting from 6 months to 5 years. RESULTS: The 20 children presenting uveitis were 4-16 years old, with etiologies as follows: 8 cases of Behçet's disease, 2 cases of Vogt-Koyanagi-Harada's disease, 1 case of sarcoidosis, 1 case of uveitis associated with coeliac disease, 1 case of toxoplasmosis, 1 case of sympathetic ophthalmia, 1 case of uveitis with streptococcal infection, 3 cases of ocular toxocarosis, and 2 cases with unknown etiology. Treatment based on the etiological findings was started in the cases of toxoplasmosis and uveitis from streptococcal infection. The others were treated with high- and then digressive-doses of corticosteroids. ANALYSIS: We have noted the high incidence of Behçet's disease in our series. Progression was marked by frequent recurrence for one case of Vogt-Koyanagi-Harada's syndrome and one case of toxoplasmosis. This study also revealed a few cases of complicated cataract. DISCUSSION: Clinical characteristics, diagnosis, and treatment of uveitis in children are discussed.

Adolescent↗

Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma).

A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma.

Aged↗

Upward gaze paralysis as the initial manifestation of HIV-infected patient: a case report.

Upward gaze palsy developed in a 23-year-old man without any other abnormal findings except pupillary light-near dissociation in ocular examination. The neuroradiologic examination was consistent with cerebral toxoplasmosis--the most frequent opportunistic infection of the brain in AIDS patients. The serologic work-up revealed a positive HIV test. Symptoms and neuroradiologic abnormality improved after treatment for cerebral toxoplasmosis. HIV infection should be considered in patients who have upward gaze paralysis and neuroimaging compatible with cerebral toxoplasmosis. Empirical treatment may alleviate the upward gaze palsy.

AIDS-Related Opportunistic Infections↗

Options for the pharmacotherapy of toxoplasmosis during pregnancy.

Toxoplasmosis infection during pregnancy can cause stillbirths, severe mental retardations or ocular disorders that can also occur later in life and have a potential to relapse. As the disease is generally asymptomatic, diagnosis relies on serological tests. Primary prevention intends to prevent the infection of the fetus, while secondary prevention aims at reducing the severity of sequelae. Preventive attitudes regarding congenital toxoplasmosis differ according to countries. In Austria and France, a nationwide programme based on the screening of seronegative pregnant women and the treatment of all seroconversions has been implemented. The UK and Norway have rejected such a screening due to the lack of evidence of its efficacy. A review of published studies showed that no randomised controlled trials have been conducted. The only available data come from retrospective studies and are methodologically flawed. The impact of chemotherapy on primary and secondary prevention still needs to be assessed. This lack of evidence results in conflicting attitudes that increase the anxiety already raised in pregnant women and doctors by the occurrence of a maternal toxoplasmosis during pregnancy. Before making any change in preventative strategy, it is of utmost importance to increase our knowledge on treatment efficacy through proper randomised trials of existing drugs and of new potentially active compounds.

Antiprotozoal Agents↗

Suspected toxoplasma-associated myocarditis in a cat.

Clinical toxoplasmosis is commonly reported in the cat, with the most consistent findings being ocular, pulmonic, hepatic, neurological, gastrointestinal and muscular abnormalities. Myocarditis, whilst frequently identified at post-mortem examination, has not been identified ante-mortem. In immunocompromised humans, myocarditis associated with toxoplasmosis is not an uncommon complication. In such cases, lymphocytic myocardial infiltration can lead to depressed myocardial function, which can be associated with congestive heart failure, rhythm disturbances and pericardial effusions. In addition, myocardial failure has been reported in immunocompetent humans associated with active toxoplasmosis [Chandenier J, Jarry G, Nassif D, Douadi Y, Paris L, Thulliez P, Bourges-Petit E, Raccurt C (2000) Congestive heart failure and myocarditis after seroconversion for toxoplasmosis in two immunocompetent patients. European Journal of Clinical Microbiological Infectious Disease 19, 375-379]. Here we describe a cat with echocardiographic changes consistent with infiltrative or inflammatory disease, and elevated IgG and IgM titres to Toxoplasma gondii. There was resolution of these myocardial changes once the toxoplasmosis was treated.

Animals↗

Immunopathogenesis of toxoplasmosis.

Toxoplasmosis is a ubiquitous infection affecting 500 million persons around the world, with a range of incidence 12%-90%, increasing with age, education, crowding and sanitary habits. Cats are the definitive host. Infection is primarily congenital but acquired ocular infection has been documented. The review focuses on the immunopathogenesis of toxoplasmosis with emphasis on the eye problem due to its morbidity. The response to infection correlates with both parasitic and retinal antigens. The clinical picture and histopathology is a reflection of the immune response which constitutes early humeral response which presents both systemically and locally primary infection and is elevated with reactivation. This is followed by the cellular response, varying from low grade monocular infilterate a total tissue destruction with response of live parasites especially in immuno-compromised patients. Penetration of the parasite and its enclosure within the parasitophorous vacuole and its eneyst all make its eradicatier impossible. This reflects the variability of antiparasitic therapy that include folate antagonists, macrolides, hydroxy naphthoquindones and fluoroquinolones. Use of corticosteroid should be limited to severe reactions and should be associated with specific therapy.

Adrenal Cortex Hormones↗

[The so-called "ocular histoplasmosis syndrome"].

The authors describe seven patients presenting with ophthalmoscopic findings typical of "presumed ocular histoplasmosis syndrome." However, no humoral antibodies could be demonstrated. Moreover, the results of skin tests were all negative even after "boostering." Hence, the diagnosis of ocular histoplasmosis had to be ruled out. Tests for listeriosis, lues, leptospirosis, ornithosis, Toxocara canis, toxoplasmosis, Larva migrans, and Candida albicans were also negative. There are evidently other, so far unknown, agents which lead to an ophthalmoscopic picture that mimics ocular histoplasmosis with its typical "punched-out lesions" and central hemorrhagic chorioretinopathy. One of these agents may be Epstein-Barr virus, because two of six patients had increased antibody levels of Epstein-Barr nuclear antigen and early antigen, indicating an active or persistent state of viral infection.

Adult↗

Innate refractoriness of the Lewis rat to toxoplasmosis is a dominant trait that is intrinsic to bone marrow-derived cells.

Toxoplasmosis is a ubiquitous parasitic infection causing a wide spectrum of diseases. It is usually asymptomatic but can lead to severe ocular and neurological disorders. Among the small-animal models available to study factors that determine susceptibility to toxoplasmosis, the rat appears to be rather similar to humans, particularly in terms of resistance to acute infection. Here, we demonstrate that the Lewis (LEW) rat strain displays an unexpected refractoriness to Toxoplasma infection. Complete resistance was assessed by both negative anti-Toxoplasma serology and lack of detection of the parasite during the course of infection. In this model, sex, age, major histocompatibility complex, and inoculum size had no effect on resistance. Interestingly, progeny from F(1) hybrid crosses between Fischer (F344) or Brown Norway susceptible rats and LEW resistant rats were also fully resistant, showing a dominant effect of the gene or set of genes. Furthermore, resistance of the LEW rat was shown to be dependent on hematopoietic cells and partially abrogated by neutralization of endogenous gamma interferon. To our knowledge, this is the first observation of a rodent strain that is refractory to Toxoplasma infection. This model is therefore an attractive and powerful tool to dissect host genetic factors involved in susceptibility to toxoplasmosis.

Animals↗

[Prospective study of pregnants and babies with risk of congenital toxoplasmosis in municipal district of Rio Grande do Sul].

This study followed up 2,126 pregnant women cared for at SUS day-care clinics (Public Health Insurance System) of the northwest of the State of Rio Grande do Sul, Brazil. After serological screening we performed a follow up of all pregnant women and their babies. Serologic tests included: IgG, IgM, IgA and IgG avidity levels, mice inoculation and polymerase chain reaction (PCR) also placentas and umbilical materials were tested using immunoperoxidase as well as clinical evaluation. Of all the pregnant women screened, 74.5% were reactive to toxoplasmosis, and 3.6% presented IgM seropositivity. At ophthalmic evaluation ten women had ocular lesions and one infant presented eye lesions and brain calcification. The presence of anti-T.gondii specific IgM throughout the entire pregnancy did not characterize acute phase infection, for this, complementary tests were necessary. The importance is underscored for attendance of the newborn of mothers presenting serology compatible with this infection even in the absence of signs and symptoms of congenital toxoplasmosis.

Animals↗

[Retinitis disclosing subacute sclerosing panencephalitis].

SSPE is a panencephalitis who involves children and who leads to death. It is due to a defective measles virus. Ophthalmologic features are frequent and may be the first manifestation of the disease. The most typical ocular involvement is retinitis which can be misdiagnosed as a toxoplasmosis.

Adult↗