Toxoplasmosis immunocompromised patients

Protozoa usually can be identified in tissue sections stained with hematoxylin and eosin or Giemsa stain however, because of the small size of the organisms and the subtle distinguishing features, an unequivocal diagnosis cannot always be made. The role of IHC in the detection of protozoal infections has been particularly valuable in cases in which the morphology of the parasite is distorted by tissue necrosis or autolysis. In addition, in immunocompromised patients, toxoplasmosis can have an unusual disseminated presentation with numerous tachyzoites without bradyzoites (Fig. 

Atovaquone is an alternative therapy for P jiroveci infection, although its efficacy is lower than that of trimethoprim-sulfamethoxazole. Standard dosing is 750 mg taken with food twice daily for 21 days. Adverse effects include fever, rash, nausea, vomiting, diarrhea, headache, and insomnia. Serious adverse effects appear to be minimal, although experience with the drug remains limited. Atovaquone has also been effective in small numbers of immunocompromised patients with toxoplasmosis unresponsive to other agents, although its role in this disease is not yet defined. 

Pyrimethamine, in combination with sulfadiazine, is first-line therapy in the treatment of toxoplasmosis, including acute infection, congenital infection, and disease in immunocompromised patients. For immunocompromised patients, high-dose therapy is required followed by chronic suppressive therapy. Folinic acid is included to limit myelosuppression. Toxicity from the combination is usually due primarily to sulfadiazine. The replacement of sulfadiazine with clindamycin provides an effective alternative regimen. 

Clinical Use. Atovaquone (Mepron) is used primarily to treat the protozoon that causes toxoplasmosis and the fungus that causes pneumocystis pneumonia in immunocompromised patients.6 This drug is not typically the primary treatment for pneumocystis, but is often reserved for patients who cannot tolerate more traditional treatments using sulfamethoxazole and trimethoprim (see Chapter 34) or pentamidine (see later). Atovaquone can also be used to prevent and treat resistant cases of malaria, and the antimalarial effects of this drug seem especially useful when combined with proguanil.48... 

Ocular toxoplasmosis is an important cause of posterior segment infection in older patients, with reports of disease presentation describing many atypical findings, including diffuse disease, multifocal lesions, and areas of involvement greater than three disc diameters in size. These individuals were not immunocompromised, but the disease severity was attributed to the decline in immune function that naturally occurs with aging. 

The esters also react readily with aryl hydrazines to give aryl hydrazone derivatives. Examples of the latter were first synthesized (prior to the availability of tetraalkyl carbonylphosphonates) from tetraalkyl methylenebisphosphonates and aryl diazonium salts, analogously to the phosphonoglyoxylate hydrazone synthesis described in a previous section. First made as possible precursors in a ketone synthesis, several of these compounds, converted to free acid salts by treatment with BTMS followed by dicyclohexylamine in methanol, proved to have unexpected inhibitory activity vs the pyrophosphate-dependent phospho-fructokinase of the parasite T. gondii, which causes a potentially lethal opportunistic infection in immunocompromised persons such as AIDS patients [94]. In fact, the 2,4-dinitrophenylhydrazone of carbonylbisphosphonic acid (as the tetrasodium salt) dramatically abated toxoplasmosis lesions in infected human foreskin fibroblasts [94]. Animal toxicity in this compound, probably arising from in vivo hydrolysis to the highly toxic hydrazine, precluded its future development, but the result remains an interesting lead. 

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