Toxoplasmosis 3rd Edition

Toxoplasma gondii is an obligate intracellular protozoan responsible for infections throughout the world in a wide range of hosts including humans. Primary infection is usually subclinical but in some patients cervical lymphadenopathy or ocular disease can be present. The toll-like receptor (TLR) is a critical pathway in initiating defense against this opportunistic protozoan, which can also be a mediator of pathology during immune dysfunction. In fact, the innate production of IL-12 requires that the parasite first be sensed by the host; innate TLRs, particularly 2, 4, 9, and 11, have an important role in this process. Infection acquired during pregnancy may cause severe damage to the fetus. In immunocompromised patients and in those with AIDS, reactivation of latent infection can cause life-threatening encephalitis. A very important aspect that has emerged in recent years concerns the possible occurrence of toxoplasmosis in patients receiving biotherapies, particularly anti-TNF-α agents for the treatment of rheumatologic diseases and other conditions. In this setting, rituximab (Rituxan) induces B-cell depletion and influ- ences T-cell immunity, which could consequently predispose patients to serious infectious complications, including cerebral toxoplasmosis. Latent toxoplasmosis is another recent clinica aspect characterized by the lifelong presence of cysts of the parasite in different host tissues, including the nervous system, and by the presence of anamnestic Toxoplasma immunoglobulin (Ig)G antibodies in the serum. Long considered asymptomatic, latent toxoplasmosis might increase the risk of schizophrenia and Parkinson’s disease; influence human personality and behavior; impair psychomotor performance; and increase the risk of suicide, traffic accidents, and the probability of the birth of male offspring. T. gondii infection can be diagnosed indirectly with serological methods and directly by Polymerase Chain Reaction (PCR), hybridisation, isolation, and histology. Whereas indirect serological methods are widely used in immunocompetent patients, definitive diagnosis in immunocompromised people is mostly undertaken by direct detection of the parasite. Pyrimethamine (Daraprim) plus sulfadiazine (Adiazine) plus folinic acid is the standard and preferred regimen against toxoplasmosis. It is recommended for: acute T. gondii infection in adult immunocompetent acute ill, pregnant women who acquire the infection after 18 weeks of gestation or in whom foetal infection is documented (positive PCR-AF), immunosuppressed patients including AIDS. Patients who do not tolerate standard regimen should be given alternative drugs such as clarithromycin, azithromycin, atovaquone and dapsone. Oral spiramicyn (Rovamycine) is the drug most frequently used in the prenatal therapy of congenital toxoplasmosis (<18 week of gestation), because of its relative lack of toxicity compared to teratogenic effects of pyrimethamine. Spiramycin is more efficacious when administered early after mother seroconversion. Trimethoprim-sulfamethoxazole (Bactrim) should be given as prophylactic regimen to HIV positive patients with CD4+ cell counts < 100/mm3 with IgG T. gondii antibodies not already receiving a PCP prevention regimen also active for toxoplasmosis, transplant patients and persons following accidental laboratory exposure