Central nervous system toxoplasmosis in HIV pathogenesis, diagnosis, and therapy
Abstract
In patients with HIV, Toxoplasma gondii is the most frequent infectious cause of focal brain lesions. Particularly in advanced HIV disease, it can cause significant morbidity and mortality. Current clinical practice involves empiric therapy with pyrimethamine and sulfadiazine, upon a presumptive diagnosis of toxoplasmic encephalitis, based on serologic, clinical, and radiological features. This approach continues to evolve, as new diagnostic strategies, such as the use of immunoglobulin G antibody titers and polymerase chain reaction, prophylaxis against opportunistic infections, and highly active antiretroviral therapy—HAART—come into play. Primary and secondary prophylaxis are the mainstay of treatment. There remains a continuing need for development of new anti-Toxoplasma therapy.
Keywords
Toxoplasmosis Antimicrob Agent Sulfadiazine Pyrimethamine Toxoplasma GondiiPreview
Unable to display preview. Download preview PDF.
References and Recommended Reading
- 1.Luft BJ, Hafner R, Korzun A, et al.: Toxoplasmic encephalitis in patients with the Acquired Immunodeficiency Syndrome. N Engl J Med 1993, 329:995–1000.PubMedCrossRefGoogle Scholar
- 2.Wallace MR, Rossetti RJ, Olsen PE:Cats and toxoplasmosis risk in HIV-infected adults. JAMA 1993, 269:76–77.PubMedCrossRefGoogle Scholar
- 3.Israelski DM, Chmiel JS, Poggensee L, et al.: Prevalence of Toxoplasma infection in a cohort of homosexual men at risk of AIDS and toxoplasmic encephalitis. J Acquir Immune Defic Syndr Hum Retrovirol 1993, 6:414–418.Google Scholar
- 4.Mariuz P, Bosler EM, Luft BJ: Toxoplasma. Curr Ther Infect Dis 1995, 562–566.Google Scholar
- 5.Richards FO, Kovacs JA, Luft BJ. Preventing Toxoplasmic Encephalitis in Persons Infected with Human Immunodeficiency Virus. Clin Infect Dis 1995, 21(suppl I):S49-S56. This article offers a comprehensive review of primary and secondary prophylaxis against toxoplasmic encephalitis in HIV patients.PubMedGoogle Scholar
- 6.Pelloux H, Dupouy-Camet J, Derouin F. A multicentre prospective study for the polymerase chain reaction detection of Toxoplasma gondii DNA in blood samples from 186 AIDS patients with suspected toxoplasmic encephalitis. AIDS 1997, 11:1888–1890.PubMedCrossRefGoogle Scholar
- 7.Porter SB, Sande MA: Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Eng J Med 1992, 327:1643–1648.CrossRefGoogle Scholar
- 8.Derouin F, Leport C, Pueyo S, et al.: Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. AIDS 1996, 10:1521–1527. This article demonstrates significantly associates IgG titers with occurrence of toxoplasmic encephalitis.PubMedCrossRefGoogle Scholar
- 9.Holliman RE, Johnson JD, Savva D: Diagnosis of cerebral toxoplasmosis in association with AIDS using the polymerase chain reaction. Scand J Infect Dis 1990, 22:243–244.PubMedGoogle Scholar
- 10.Van de ven E, Melchers W, Galama J, et al.: Identification of Toxoplasma gondii infections by B1 gene amplification. J Clin Microbiol 1991, 29:2120–2124.PubMedGoogle Scholar
- 11.Grover CM, Thulliez P, Remington JS, Boothroyd JC: Rapid prenatal diagnosis of congenital Toxoplasma infection by using polymerase chain reaction and amniotic fluid. J Clin Microbiol 1990, 28:2297–2301.PubMedGoogle Scholar
- 12.Dupouy-Camet J, Lavareda De Souza S, Bougnoux ME, et al.: Preventing congenital toxoplasmosis. Lancet 1990, 336:1018.Google Scholar
- 13.Brezin AP, Silveira C, Thulliez P, et al.: Analysis of aqueous humor in ocular toxoplasmosis. N Engl J Med 1991, 324:699.PubMedGoogle Scholar
- 14.Gianotti N, Cinque P, Castagna A, et al.: Diagnosis of toxoplasmic encephalitis in HIV infected patients. AIDS 1997, 11:1529–1530.PubMedGoogle Scholar
- 15.Novati R, Castagna A, Morsica G, et al.: Polymerase chain reaction for Toxoplasma gondii DNA in the cerebrospinal fluid of AIDS patients with focal brain lesions. AIDS 1994, 8:1691–1694.PubMedCrossRefGoogle Scholar
- 16.Dupon M, Cazenave J, Pellegrin JL, et al.: Detection of Toxoplasma gondii by PCR and Tissue culture in Cerebrospinal Fluid and Blood of Human Immunodeficiency Virus Seropositive Patients. J Clin Microbiol 1995, 33:2421–2426.PubMedGoogle Scholar
- 17.Rodriguez JC, Martinez MM, Martinez AR, Royo G: Evaluation of different techniques in the diagnosis of Toxoplasma encephalitis. J Med Microbiol 1997, 46:597–601.PubMedGoogle Scholar
- 18.Antinori A, Ammassari A, De Luca, et al.: Diagnosis of AIDS related focal brain lesions: a decision making analysis based on clinical and neuroradiological characteristics combined with polymerase chain reaction assay in cerebrospinal fluid. Neurology 1997; 48:687–694.PubMedGoogle Scholar
- 19.Luft BJ, Remington JS: Toxoplasmic Encephalitis in AIDS. Clin Infect Dis 1992, 15:211–222. This article reviews the current approach to diagnosis and therapy of toxoplasmic encephalitis in HIV infected patients.PubMedGoogle Scholar
- 20.Ramsey RG, Gean AD: Neuroimaging of AIDS. I. Central nervous system toxoplasmosis. Neuroimaging Clin N Am 1997, 7(2):171–186.PubMedGoogle Scholar
- 21.O’Doherty MJ, Barrington SF, Campbell M, et al.: PET scanning and the human immunodeficiency virus positive patient. J Nucl Med 1997, 38:1575–1583.PubMedGoogle Scholar
- 22.Ammassari A, Scoppettuolo G, Murri R, et al.: Changing disease patterns in Focal Brain Lesion-Causing disorders in AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1998, 18:265–371. Clinically important study.Google Scholar
- 23.Bishburg E, Eng RH, Slim J, Perez G, et al.: Brain lesions in patients with acquired immunodeficiency syndrome. Arch Internal Med 1989, 149:941–943.CrossRefGoogle Scholar
- 24.Raffi F, Aboulker JP, Michelet C, et al.: A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in 186 AIDS patients. AIDS 1997, 11:177–184. These authors propose an algorithm for the probability of Toxoplasmic encephalitis in the HIV patient based on neuroradiologic finding, serology against Toxoplasma gondii, and antiprotozoal prophylaxis.PubMedCrossRefGoogle Scholar
- 25.Girard PM, Landman R, Gaudebout C, et al.: Dapsonepyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystic carinii pneumonia and toxoplasmosis in HIV infection. N Engl J Med 1993, 328:1514–1520.PubMedCrossRefGoogle Scholar
- 26.Antinori A, Murri R, Ammassari A, et al.: Aerosolized pentamidine, cotrimoxazole and dapsone-pyrimethamine for primary prophylaxis of Pneumocystic carinii pneumonia and toxoplasmosis in HIV infection. AIDS 1995, 9:1343–1350.PubMedCrossRefGoogle Scholar
- 27.Wong SY, Remington J: Toxoplasmosis in the setting of AIDS. In Medical Management of AIDS. Edited by Broder S, Merigan TC Jr, Bolognesis D. Baltimore: Williams and Wilkins; 1994:223–258.Google Scholar
- 28.Gatti G, Malena M, Casazza R, et al.: Penetration of Clindamycin and Its Metabolite N-Demethylclindamycin into Cerebrospinal fluid following intravenous infusion of clindamycin phosphate in patients with AIDS. Antimicrob Agents Chemother 1998, 42:3104–117.Google Scholar
- 29.1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. Washington DC: US Department of Health and Human Services; 1999 48:RR-10. Very useful guidelines.Google Scholar
- 30.Torre D, Casari S, Speranza F, et al.: Randomized trial of Trimethroprim-Sulfamethoxazole versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients with AIDS. Antimicrob Agents Chemother 1998, 42:1346–1349.PubMedGoogle Scholar
- 31.Ribera E, Fernandez-Sola A, Juste C, et al.: Comparison of High and Low doses of Trimethroprim-Sulfamethoxazole for Primary Prevention of Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients. Clin Infect Dis 1999, 29:1461–1466.PubMedCrossRefGoogle Scholar
- 32.Cantin L, Chamberland S: In vitro evaluation of the activities of azithromycin alone and combination with pyrimethamine against Toxoplasma gondii. Antimicrob Agents Chemother 1993, 37:1993–1996.PubMedGoogle Scholar
- 33.Fernandez JM, Leport C, Molart P, et al.: Pyrimethamineclarithromycin combination for therapy of acute Toxoplasma encephalitis in patients with AIDS. Antimicrob Agents Chemother 1991, 35:2049–2052.Google Scholar
- 34.Djurkovid-Djakovic O, Nikolic T, Robert-Gangneux F, et al.: Synergistic effect of Clindamycin and Atovaquone in Acute Murine Toxoplasmosis. Antimicrob Agents Chemother 1999, 43:2240–2244.Google Scholar
- 35.Khan A, Slifer T, Araujo F, et al.: Quinupristin-Dalfopristin is active against Toxoplasma gondii. Antimicrob Agents Chemother 1999, 43:2043–2045.PubMedGoogle Scholar
- 36.Khan A, Slifer T, Araujo F, et al.: Trovafloxin is active against Toxoplasma gondii. Antimicrob Agents Chemother 1996, 40:1855–1859.PubMedGoogle Scholar
- 37.Estes R, Vogel N, Mack D, Mcleod R: Paclitaxel arrests growth of intracellular Toxoplasma gondii. Antimicrob Agents Chemother 1998, 42:2036–2040.PubMedGoogle Scholar
- 38.Berens R, Krug E, Nash P, Curiel T: Selection and Characterization of Toxoplasma gondii mutants resistant to Artemisin. J Infect Dis 1998, 177:1128–1131.PubMedCrossRefGoogle Scholar
- 39.Torres R, Weinberg W, Stansell J, et al.: Atovaquone for Salvage Treatment and Suppression of Toxoplasmic Encephalitis in Patients with AIDS. Clin Infect Dis 1997, 24:422–429.PubMedGoogle Scholar