Acute toxoplasmosis

Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. The combination of sulfadiazine with pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthetic pathway blockade (Figure 46-2). The dosage of sulfadiazine is 1 g four times daily, with pyrimethamine given as a 75-mg loading dose followed by a 25-mg once-daily dose. Folinic acid, 10 mg orally each day, should also be administered to minimize bone marrow suppression. 

R4. Remington, J. S., Miller, M. J., and Brownlee, I., IgM antibodies in acute toxoplasmosis 1. Diagnostic significance in congenital cases and a method for their rapid demonstration. Pediatrics 41, 1082-1091 (1968). 

King MD, Ehrich MF, Lindsay DS. Effects of recent methyl mercury exposure on acute toxoplasmosis in CBA/J mice. J Eukaryot Microbiol 2001 48(Suppl. 1) 199S-200S. 

Untreated acute toxoplasmosis among pregnant women can lead to infection of the fetus via transplacental transmission (Varella et ah, 2009.). At first examination, newborns affected by congenital infection may seem normal however, serious sequelae, such as neurological impairment and blindness, can develop witiiin a few years lafer (Dunn et ah, 1999 Remington et ah, 2006 Safadi et ah, 2003.). 

Another outbreak occurred in British Columbia, Canada in 1995, and 110 acute toxoplasmosis cases were identified. The epidemiological studies demonstrated that the outbreak was consistent with a waterborne source and implicated contaminated municipal drinking water (Bowie et al., 1997). 

In 1969, an oufbreak of acute toxoplasmosis involved five medical sfudenfs from Cornell Medical College. The sfudenfs all afe rare hamburger af fhe same place, on fhe same nighf, and evidence indicates fhaf fhis was fhe vehicle for fransmission of fhe infection (Kean et ah, 1969). 

Bonametti, A. M., Passes, J. N., da Silva, E. M. K., and Macedo, Z. S. (1997b). Probable transmission of acute toxoplasmosis through breast feeding. /. Trop. Pediatr. 43,116. 

Neves, E. S., Bicudo, L. N., Al Curi, E., Carregal, E., Bueno, W. F., Ferreira, R. G., Amendoeira, M. R., Benchimol, E., and Fernandes, O. (2009). Acute toxoplasmosis clinical-laboratorial aspects and ophthalmologic evaluation in a cohort of immunocompetent patients. Mem. Inst. Oswaldo Cruz 104, 393-396. 

Varella, I. S., Canti, I. C. T., Santos, B. R., Coppini, A. Z., Argondizzo, L. C., Tonin, C., and Wagner, M. B. (2009). Prevalence of acute toxoplasmosis infection among 41, 112 pregnant women and the mother-to-child transmission rate in a public hospital in South Brazil. Mem. Inst. Oswaldo Cruz 104, 383-388. 

Wang, X. and Suzuki, Y. (2007). Microglia produces IFN-gamma independently from T-cells during acute toxoplasmosis in the brain. /. Interferon Cytokine Res. 27, 599-695. 

Suzuki Y, Joh K, Kobayashi A. Tumor necrosis factor-independent protective effect of recombinant IFN-gamma against acute toxoplasmosis in T-cell deficient mice. J Immunol 1991 147 2728-2733. 

Apicomplexan parasites cause life threatening diseases like malaria, cryptosporid-iosis, toxoplasmosis, coccidiosis. Suberic acid bisdimethylamide which also inhibits HDA selechvely arrests tumor cells as opposed to normal mammalian cells, has an in vivo cytostatic effect against the acute murine malaria Plasmodium berghei (Andrews et al, 2000). 

Sulfonamides are used for controlling urinary tract infections, acute and chronic lung infections (norcadiosis), protozoan infections of the nervous system (i.e., toxoplasmosis), and a variety of infections in humans and livestock. Their mode of activity is by inhibiting the multiplication of bacteria by competitively inhibiting para-aminobenzioc acid (PABA) in the folic acid metabolism cycle (O Neil et al., 2001). More specifically, they block the synthesis of folic acid in bacteria as the drugs are structurally similar to PABA. Folic acid is essential to the synthesis of amino acids and nucleic acids. In bacteria, folic acid is synthesized from PABA... 

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. 

According to the CDC, the diagnosis of AIDS constitutes certain opportunistic infections, neoplasms, encephalopathy or wasting syndrome in the presence of HIV infection. In 1993, the CDC expanded the criteria to also include CD4+ T-cell count below 200 cells/p,l in the presence of HIV infection. The most common opportunistic infections includepneumocystis carinii pneumonia, pneumonitis, toxoplasmosis, mycobacterial disease, recurrent herpes simplex virus infection and/or cytomegalovirus infection. Kaposi s sarcoma is the most common form of cancer. HIV-related nervous system diseases include acute septic meningitis, AIDS dementia complex, subacute encephalitis, HIV encephalopathy and CNS opportunistic infections and neoplasm. 

The first scientific report of an orally transmitted outbreak of Chagas disease in Brazil was made in 1968 (Nery-Guimaraes et ah, 1968). This occurred in the district of Teutonia, municipality of Estrela (Rio Grande do Sul state) in the year 1965, between March 13 and March 22. Seventeen people from an Agricultural School (workers, students, and lecturers that usually had meals there) fell sick. The initial unconfirmed diagnosis was typhoid fever. Other possible diagnoses like infectious hepatitis, toxoplasmosis, infectious mononucleosis, and food poisoning were also discarded. Then, some of the infected people presented with clinical symptoms of acute myocarditis, and, based on clinical observations,... 

Acute viral hepatitis, acute salmonellosis, measles, bacterial sepsis, histoplasmosis, leptospirosis, malaria, mononucleosis, Bang s disease, visceral leishmaniasis (22), rickettsioses, toxoplasmosis, tularaemia, schistosomiasis, etc. 

A large bibliography exists from the 1940 s related to crystalluria and acute kidney injury associated with the use of sulfadiazine [1, 10, 11]. Sulfadiazine disappeared from clinical use for a long time until it re-emerged again in the AIDS era. More recently, the number of reports in adults and children has increased substantially because of the use of sulfadiazine and pyrimethamine, as the treatment of choice for cerebral toxoplasmosis associated with AIDS, other immunosuppressive states or specific infections [7, 12-35]. Acute kidney injury secondary to sulfadiazine crystalluria has been also reported in renal transplant patients [36, 37]. 

Figure 1. Sulfadiazine nephrotoxicity (crystalluria and acute renal failure). 35 year old man with AIDS and cerebral toxoplasmosis treated for 33 days with 4-6 g/dayofsulfadiazine.The patient received oral hydration and possibly had an episode of transient renal impairment during days 8-13. By day 29 of treatment, crystalluria, hematuria, flank pain, renal calculi, and acute renal failure developed. Urine was alkalinized late in the course.

The combination of pyrimethamine and sulfadiazine is the most effective regimen for acute therapy of acquired immune deficiency syndrome (AIDS)-related CNS toxoplasmosis. Therapy with this combination should be continued for at least 3 weeks, but 6 weeks of treatment is recommended for more severely ill patients. 

Derouin, R, Ahnadany, R., Chau, R, Rouveix, B., and Pocidalo, J. J. (1992). Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis. Antimicrob. Agents Chemother. 36, 997—KXll. 

Spiramycin, which concentrates in placental tissue, is used to treat acute acquired toxoplasmosis in pregnancy to prevent transmission to the fetus. If fetal infection is detected, the combination of pyrimethamine and sulfadiazine is administered to the mother (only after the first 12-14 weeks of pregnancy) and to the newborn in the postnatal period. 

However, NO may also have a role in inhibiting infectious processes. Neutralization of TNF and down-regulation of iNOS promote induction of acute cerebral toxoplasmosis and enhanced pathology in mice chronically infected with Toxoplasma gondii (Gazzinelli et al., 1993). However, N-monomethyl-L-arginine (NMMA) does not affect the antitoxoplasma activity of TNF and IL-6 produced by human microglia in vitro (Chao et al.,... 

Gazzinelli, R. T., Eltoum, I., Wynn, T. A., and Sher, A. (1993). Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNFa and correlates with the down regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. /. Immunol. 151, 3672-3681. 

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