CNS-TOXOPLASMOSIS - CASE STUDY

Anamnesis:

	The patient, K. H. Saraj, a young man 30 years old, came to Jordan from YAR 05-December-2009 complaining of fever for one month duration with lethargy. 17-November-2009, when he was trying to travel to Jordan, his condition deteriorated dramatically and went to coma for what the travel was post bonded. CT-scan and MRI performed to him and several investigations were performed. Lab investigations done for him: HBc-Ab(IgG) positive 0.004 with toxoplasma IgG (Automated ELISA) positive 918 IU/ml. These data achieved 18-November-2009. WBC was 21.2 K/uL with neutrophils 92.4% (done 19-November-2009). WBC was 19.3 X10*9/L with neutrophils 80% 20-november-2009. Toxo IgG (Axsym) positive 26.9 IU/ml in 22-November-2009. Toxo IgG (Axsym) positive 26.7 IU/ml in 24-November-2009. WBC 7.46 K/uL  with neutrophils 79.7%, GGT 38 IU/L recorded 26-November-2009. K+  was 2.8 mmol/L in 29-November-2009. K+  corrected to 3.4 mmol/L in 01-December-2009. SGPT (ALT) was 66 IU/L and SGOT(AST) 40 IU/L in 02-December-2009. The patient was put in mannitol and dexametasone pyrimethamine and clindamycin. He was also covered with antibiotics and aniviral and anti-tbc drugs. The report provided with the patient confirming that the patient was at admission comatose with dilated both pupils  and bradycardia 30/min. The patient slowly regained consciousness and started to recover and was oriented with normal vital signs before the transfer.
	The patient was seen in the ward at Shmaisani hospital. He had severe headache and inability to walk with still signs of lethargy and projectile vomiting with Foleys catheter. He was responding to verbal commands and moving four limbs with good power. There was no sensory deficit with slight meningism. There was massive rash all over the body and yellow skin and eyes.
	MRI of the brain was done 07-December-2009 and MRA of the brain with MRI of the brain with contrast repeated 08-December-2009 showing the subependymar mass in the region between the head of the right caudate nucleus and the anterior commissure. There was no aneurysm and there was still enhancement of the ring around the mass, which slightly shrunken in comparison to the MRI performed 17-Novemeber-2009.
	Lab investigations were performed and HIV-1 & 2 antibody were negative. Toxoplasma IgG was 17.5 IU/ml, SGOT 97.0 U/L, SGPT 209.0 U/L LDH 545.0 U/L GGT 67.0 U/L Folate serum level 10.0 NG/ml done 08-December-2009.
	The patient was treated for toxoplasmic encephalitis with abscess and the patient projectile vomiting stopped and he could walk the third post-admission day and the Foleys catheter was removed 10-December-2009. He admitted that the blurred vision disappeared. Chest and abdomino-pelvic CT-scan done 11-December-2009 was normal.
	Gradual tapering of dexametasone started 10-December-2009. Mannitol was stopped 11-December-2009. CD4-Lymphocyte count 465 cell/uL and SPECT was performed by Tl-201 13-December-2009 confirming no evidence of active lesion in the brain  and the patient was discharged 14-December-2009.

MRI brain showing the lesion 17-November-2009

MRI of the brain showing the same lesion 08-December-2009 confirming slight regression in size.

	The patient, then rapidly deteriorated in Yemen and was admitted to the local hospital with severe impairment of the level of consciousness with right sided panophthalmoplegia  and aggressive treatment with mannitol, vancomycin, antifungal and acyclovir was started.
	MRI performed there was not informative and the MRA was looking with beaded arteries. ANCA was positive. By telephone communication it was suggested that the patient has vasculitis. The patient was sent back to Jordan and was admitted to the ICU of Shmaisani hospital. The patient is no locked in syndrome with right sided plegia and some times yawning. He had nuchal rigidity with high fever.
	The respiratory drive was compromised but he was not in need for ventilation. MRI with contrast with MRA and MRV done ruled out the presence of beaded arteries  and the presence of massive meningoencephalitis of the deep basal ganglia both sides with involvement of the tentorium and subtentorial structures. There was considerable dilatation of the ventricular system. ANCA was repeated twice and it was negative. The patient was started with the same treatment as In Yemen and external drain was inserted to the right lateral ventricle. The CSF was yellowish and sent for all possible investigations. Only yeast could be found in one specimen and was not found in others. The pressure of the CSF was almost normal and mannitol was stopped.  All virology studies were normal and blood for CXS was negative. Duflucan was increase and the toxoplasmosis drugs were all the time kept.  Meropnem was started 1 gm QTD.
	HIV tests were repeated and they were negative. The patient was given petaglobin over three days without any signs of improvement.
	The external drain was removed after 7 days  and 2 days later tapering the dexametasone was started. The patient after slight improvement during the first week started to show gradual deterioration 3 days after tapering dexametasone, for what it was put back in track.
	The patient progressed signs of decerebration with flexor spasms, for what senimet was given and the next day Liorezal 5 mg was added. The patients rigidity disappeared and the respiratory drive got worse, for what Liorezal was stopped.
	Two days later after stopping Liorezal the patient showed slight improvement in the motor functions and the rigidity disappeared, which means that he got severe sensitivity to Liorezal.
	MRI of the brain with contrast was repeated 11-February-2010 which showed dramatic deterioration of the lesion with involvement of the temporal lobes more to the left and the pons. CSF was obtained through the old ventricular catheter site and sent for routine and antitbc PCR. The old investigated CSF for fungi needs 45 days to identify the type of fungi, which could be negative.

	The patient in 12-February-2010 showing slight improvement, and due to financial problems the patient relatives decided to transfer him back to Yemen.
	The patient has very aggressive meningo-encephalitis of protracted and relapsing and remitting character. Covering all the causative possible cause, the morphologic changes got worse and worse. Could toxoplasmosis can lead to such events, still a dilemma.

Toxoplasmosis in HIV-infected patients

INTRODUCTION — Toxoplasmosis, an infection with a worldwide distribution, is caused by the intracellular protozoan parasite, Toxoplasma gondii. Immunocompetent persons with primary infection are usually asymptomatic, but latent infection can persist for the life of the host.

In immunosuppressed patients, especially patients with the acquired immunodeficiency syndrome (AIDS), the parasite can reactivate and cause disease, usually when the CD4 lymphocyte count falls below 100 cells/µL. All patients with human immunodeficiency virus (HIV) infection should be screened for T. gondii antibodies. Counseling on preventing toxoplasmosis should be given to those who are seronegative and prophylaxis initiated, when appropriate, for seropositive patients.

EPIDEMIOLOGY

Prevalence of infection — Seroprevalence rates of toxoplasmosis vary substantially among different countries (eg, approximately 15 percent in the United States to more than 50 percent in certain European countries). Among HIV-infected patients, seroprevalence of antibodies to T. gondii mirror rates of seropositivity in the general population. Among 2525 women in the United States, for example, the T. gondii seroprevalence was 15 percent and did not differ based upon whether or not the individual had HIV. Those with HIV were more likely to have antibodies to T. gondii if they were 50 years of age or born outside of the United States. In patients with AIDS, there is no higher incidence of toxoplasmosis in cat owners compared to non-cat owners.

Patients with AIDS and <100 CD4 cells/µL, who are toxoplasma seropositive, have an approximately 30 percent probability of developing reactivated toxoplasmosis if they are not receiving effective prophylaxis. The most common site of reactivation is the central nervous system (CNS); toxoplasmosis is the most common parasitic CNS opportunistic infection (OI) in AIDS patients , except in patients who are on appropriate prophylaxis.

Toxoplasmic encephalitis — The incidence of toxoplasmic encephalitis in AIDS patients reflects seropositivity rates in this population; HIV-infected patients from Florida, for example, had a higher seroprevalence of T. gondii antibodies and a greater prevalence of toxoplasmic encephalitis in one study. However, the introduction of anti-toxoplasma prophylaxis and highly active antiretroviral therapy (HAART) has altered the occurrence of toxoplasmic encephalitis like other OIs. In the Multicenter AIDS Cohort Study (MACS), the incidence of CNS toxoplasmosis decreased from 5.4 per 1000 person-years in 1990 to 1992 to 3.8 per 1000 person-years in 1993 to 1995 and, 2.2 per 1000 person-years in 1996 to 1998 after HAART began to be widely used.

Extracerebral toxoplasmosis — It is much harder to determine the incidence of extracerebral toxoplasmosis. Most of the available data are from before the introduction of HAART and from France where the seroprevalence to T. gondii is high. In one French series of 1,699 HIV-infected patients, for example, the overall incidence of toxoplasmosis was 1.53 cases per 100 person-years for the years 1988 to 1995 (compared to 5.4 or 3.8 cases per 1000 person-years in the United States). The distribution of extracerebral cases is illustrated by the following: In the series of 1,699 patients, 116 cases of confirmed, probable or possible toxoplasmosis was diagnosed; cerebral toxoplasmosis accounted for 89 percent, with pulmonary, ocular, and disseminated infection responsible for 6, 3.5, and 1.7 percent of cases, respectively. Another French series of 199 HIV-infected patients with extracerebral toxoplasmosis evaluated between 1990 and 1992 estimated that the prevalence of extracerebral toxoplasmosis among AIDS patients was 1.5 to 2 percent. Among these selected patients, eye involvement occurred in 50 percent, lungs in 26 percent, two or more extracerebral sites in 11.5 percent, and peripheral blood, heart, and bone marrow in 3 percent each. Involvement of the bladder, pharynx, skin, liver, lymph nodes, conus medullaris, and pericardium also were demonstrated in rare cases. Widespread distribution may be more common pathologically than clinically appreciated. This was suggested in an autopsy study in which the most common extracerebral sites of toxoplasmosis in HIV-infected patients were the heart, lungs, and pancreas with 91, 61, and 26 percent of cases, respectively. The most prominent risk factor for the development of extracerebral toxoplasmosis is advanced immunosuppression (mean CD4 counts of 57 and 58 cells/µL in two of the French series). Concurrent CNS disease was present in 41 percent of patients in the report of 199 extracerebral cases.

CLINICAL PRESENTATION — As noted above, when T. gondii reactivates in a patient with AIDS, it most commonly does so in the CNS leading to cerebral abscesses. The clinical manifestations of toxoplasmosis in immunocompetent patients are discussed separately.

Toxoplasmic encephalitis — Patients with cerebral toxoplasmosis typically present with headache. In one retrospective review of 115 cases, 55, 52, and 47 percent had headache, confusion, and fever, respectively. Focal neurologic deficits or seizures are also common. Fever is usually, but not reliably, present. Dull affect may be due to global encephalitis but more profound mental status changes, especially accompanied by nausea or vomiting, usually indicates elevated intracranial pressure.

Extracerebral toxoplasmosis

	Pneumonitis — Pneumonitis, as an extracerebral manifestation of toxoplasmosis, presents with fever, dyspnea and non-productive cough. Chest radiographs typically have reticulonodular infiltrates. The clinical picture may be indistinguishable from Pneumocystis jiroveci (formerly carinii) pneumonia (PCP). Some have suggested that a blood level of lactate dehydrogenase >600 U/L is more likely to be associated with toxoplasmosis than PCP. However, others have found that LDH is elevated in both of these infections.
	Chorioretinitis — Patients with toxoplasmic chorioretinitis (a posterior uveitis) usually present with eye pain and decreased visual acuity. These symptoms and signs do not distinguish this entity from other ocular infections in HIV, especially cytomegalovirus (CMV) retinitis. Toxoplasmic chorioretinitis appears as raised yellow-white, cottony lesions in a non-vascular distribution, unlike the perivascular exudates of CMV retinitis. Vitreal inflammation is usually present in contrast to ocular toxoplasmosis in immunocompetent patients. Chorioretinitis due to T. gondii can rarely mimic acute retinal necrosis. Up to 63 percent of AIDS patients with toxoplasma chorioretinitis will have concurrent CNS lesions.
	Other manifestations — Toxoplasmosis can rarely present with involvement of a variety of other sites in patients with AIDS including: gastrointestinal tract, liver, musculoskeletal system, heart, bone marrow, bladder, spinal cord, and orchitis. In the French series, toxoplasmosis of the pancreas or muscular system did not occur in the absence of involvement at other sites. Nine patients with disseminated toxoplasmosis presenting with septic shock were reported from France; in two patients this appeared to be primary infection.

DIAGNOSIS — Toxoplasmosis frequently enters the differential diagnosis in an AIDS patient with focal brain lesions. The vast majority of patients with toxoplasma encephalitis are seropositive for anti-toxoplasma IgG antibodies. Anti-toxoplasma IgM antibodies are usually absent and quantitative IgG antibody titers are not helpful. The absence of antibodies to toxoplasma makes the diagnosis less likely, but does not exclude the possibility of TE.

To establish a definitive diagnosis in patients with extracerebral toxoplasmosis, the demonstration of tachyzoites in tissue or fluid, such as BAL, is usually required.

Cerebral toxoplasmosis — Most AIDS patients with cerebral toxoplasmosis have multiple, ring-enhancing brain lesions often associated with edema. In a report of 45 patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI), 31 (69 percent) had multiple lesions and 14 had single lesions. There is a predilection for involvement of the basal ganglia.

  MRI versus CT — Magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for identifying these lesions. In one prospective study of 50 AIDS patients with neurologic symptoms, for example, MRI detected abnormalities that influenced diagnosis and treatment in 40 percent, which were not characterized by CT.

However, there is an extensive differential diagnosis for brain lesions in AIDS patients and the appearance by either CT or MRI does not adequately distinguish among these. Toxoplasmosis and CNS lymphoma are the two most common entities (representing 50 and 30 percent, respectively), but other infections, including cryptococcosis, histoplasmosis, aspergillosis, tuberculosis and trypanosomiasis may also cause brain abscesses in patients with AIDS.

  SPECT imaging — Thallium single photon emission computed tomography (SPECT) and positron emission tomography (PET) can be useful in distinguishing toxoplasmosis or other infections from CNS lymphoma. Lymphoma has greater thallium uptake on SPECT and greater glucose and methionine metabolism on PET than neurotoxoplasmosis or other infections.

  Brain biopsy — Definitive diagnosis of cerebral toxoplasmosis is made by pathologic examination of brain tissue obtained by open or stereotactic brain biopsy. Organisms are demonstrated on hematoxylin and eosin stains; some laboratories also use immunoperoxidase staining which may increase diagnostic sensitivity.

However, there is morbidity and even mortality associated with the procedure. In one series of 136 patients, morbidity and mortality of brain biopsy was 12 and 2 percent, respectively. Morbidity rates have been reported to be 3 to 4 percent. Due to these concerns, it is common practice to presumptively diagnose and treat cerebral toxoplasmosis in AIDS patients if the clinical suspicion is high. A presumptive diagnosis can be made if the patient has a CD4 cell count <100/µL and: Is seropositive for T. gondii IgG antibody Has not been receiving effective prophylaxis for toxoplasma. Brain imaging demonstrates a typical radiographic appearance (eg, multiple ring-enhancing lesions)

If these three criteria are present, there is a 90 percent probability that the diagnosis is toxoplasmosis, and thus, it is common practice to treat empirically for toxoplasmosis. If a solitary lesion is detected, even if toxoplasma serology is positive, CNS lymphoma rises on the differential diagnosis list. If all three of the above criteria are not met, biopsy or other diagnostic tests should be performed. Brain biopsy should also be performed if the patient does not respond to empiric therapy, on the basis on clinical or radiographic improvement.

A group has questioned the reliability of the presumptive diagnostic approach in favor of earlier biopsy. In one study, the positive predictive value of the Centers for Disease Control and Prevention (CDC) criteria for the diagnosis of toxoplasmic encephalitis declined from 100 to 39 percent from 1991 to 1996. An increase in use of prophylaxis against toxoplasmosis and increases in other causes of CNS focal lesions were deemed largely responsible for this difference.

Polymerase chain reaction (PCR) testing for other pathogens (eg, Epstein-Barr virus [EBV], JC virus, Mycobacterium tuberculosis, Cryptococcus neoformans) can be considered in patients with focal brain lesions who were already taking prophylactic antibiotics for toxoplasmosis or were seronegative. The prevalence of these other infections in HIV-infected patients and other clinical clues from the presentation should influence which specific tests are ordered.

  CSF analysis — Cerebrospinal fluid (CSF) may have mild mononuclear pleocytosis and elevated protein. T. gondii can be detected in CSF by DNA amplification in most patients with CNS infection. Tachyzoites can sometimes be seen on cytocentrifuged cerebrospinal fluid samples stained with Giemsa.

TREATMENT — A number of therapies are available for the treatment of toxoplasmosis. Toxoplasmic encephalitis generally responds promptly to treatment. Lack of either clinical or radiographic improvement within 10 to 14 days of empiric therapy for toxoplasmosis should raise the possibility of an alternative diagnosis. Extracerebral toxoplasmosis is treated with the same regimens as toxoplasmic encephalitis, although the response may not be as favorable.

The following are treatment guidelines from the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH, and Infectious Diseases Society of America (IDSA):

First-line therapy — Two combination regimens are considered to be first choices for the treatment of toxoplasmosis. All pyrimethamine regimens should include folinic acid to prevent drug-induced hematologic toxicity (10 to 25 mg/day PO). Pyrimethamine (200 mg loading dose PO followed by 75 mg/day) plus sulfadiazine (6 to 8 g/day PO in four divided doses). For those patients who cannot take sulfadiazine due to intolerance or history of allergy, pyrimethamine (200 mg loading dose PO followed by 75 mg/day) plus clindamycin (600 to 1200 mg IV or 450 mg PO four times a day) is recommended.

Pyrimethamine plus sulfadiazine has a higher incidence of cutaneous hypersensitivity reactions compared with pyrimethamine plus clindamycin but may have a lower incidence of relapse. Patients receiving sulfadiazine therapy do not require additional TMP-SMX for PCP prophylaxis. One study documented equivalent pharmacokinetic parameters for 2000 mg of sulfadiazine administered twice daily compared to 1000 mg given four times a day. Treatment for pregnant females is the same as in nonpregnant females.

Alternative regimens — Several alternative regimens have been used, generally in patients who are unable to tolerate either sulfadiazine or clindamycin: Pyrimethamine (200 mg loading dose PO followed by 75 mg/day) plus azithromycin (1200 to 1500 mg PO once daily) Pyrimethamine (200 mg loading dose PO followed by 75 mg/day) plus atovaquone (750 mg PO four times a day) Sulfadiazine (1500 mg four times a day) plus atovaquone (1500 mg twice daily)

If atovaquone is used, measuring plasma levels might be helpful since there is significant individual variation in drug absorption and higher plasma concentrations are associated with better outcomes.

A pilot, multicenter, randomized prospective trial evaluated the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) compared to standard therapy with pyrimethamine-sulfadiazine. Seventy-seven patients were randomly assigned to receive TMP (10 mg/kg/day) and SMX (50 mg/kg/day) as acute therapy for four weeks followed by maintenance therapy for three months at half of the original dosage. There was no statistically significant difference in clinical efficacy between the two arms. Adverse effects were more common in the patients treated with pyrimethamine-sulfadiazine. Trimethoprim-sulfamethoxazole may be an effective alternative treatment regimen, particularly in resource-poor settings.

In critically ill patients, intravenous administration of TMP 10 mg/kg/d + SMX 50 mg/kg/d, can be considered, although is less effective.

As above, pyrimethamine therapy should always be accompanied by the administration of folinic acid (10 to 25 mg/day PO). Some of these regimens, especially those using atovaquone, have been tried as salvage therapy in patients failing to respond to a first-line regimen. However, reconsideration of the diagnosis should be the first response to a patient who appears to be failing therapy.

Duration of therapy — For patients who respond, the duration of therapy is typically six weeks at the doses recommended above. Following that treatment, it is usually safe to decrease to a lower dose for secondary prophylaxis (chronic suppressive therapy).

Steroids — Adjunctive corticosteroids should be used for patients with radiographic evidence of midline shift, signs of critically elevated intracranial pressure or clinical deterioration within the first 48 hours of therapy. Dexamethasone (4 mg every six hours) is usually chosen and is generally tapered over several days.

When corticosteroids are used, it may be difficult to assess the clinical response to antibiotics since the rapid improvement in symptoms may be due to steroid therapy. Radiographic assessment is also affected since the corticosteroids will reduce the intensity of ring-enhancement and the amount of surrounding edema. If steroids are used, patients should also be carefully monitored for the development of other opportunistic infections.

Anticonvulsants — Anticonvulsants should be administered to patients with a history of seizures, but should not be given routinely for prophylaxis to all patients with the presumed diagnosis of TE. Careful attention needs to be paid to any potential drug interactions.

Monitoring of therapy — Monitoring of patients includes careful clinical evaluations, serial brain imaging, and assessment of any adverse effects of therapy. There is no value to serial assessment of IgG toxoplasma antibody titers.

Common side effects of pyrimethamine include rash, nausea, and bone marrow suppression. Higher doses of leucovorin up to 50 to 100 mg daily can be considered for management of hematologic abnormalities. Sulfadiazine use can lead to rash, fever, leukopenia, hepatitis, nausea, vomiting, diarrhea, and crystalluria. Clindamycin use can also lead to fever, rash, nausea and diarrhea related to production of Clostridium difficile toxin.

Response to therapy — Clinical improvement usually precedes radiographic improvement. Thus, a careful daily neurologic examination is more important than radiographic studies in assessing the response to therapy during the first two weeks of treatment. Radiographic reassessment should be deferred for two to three weeks unless the patient has not demonstrated clinical improvement within the first week or has shown any worsening.

The literature on response to therapy is hampered by presumptive diagnoses, cross-over treatments, and discontinuation for toxicity rather than lack of clinical response. There are no randomized, double-blind trials. The comparative trials on different treatment regimens suggest that approximately 80 percent of patients demonstrate clinical and radiologic responses.

One study focused on the timing of the response in 49 patients treated with pyrimethamine plus clindamycin [22]. Seventy-one percent responded overall with 32 of the 35 patients demonstrating improvement of at least 50 percent of baseline abnormalities by day 14 of therapy. The authors concluded that early neurologic deterioration or lack of neurologic improvement (except for headache and seizures) by day 10 to 14 should raise the possibility of an alternative diagnosis and such patients should be considered for brain biopsy. (See "Approach to HIV-infected patients with central nervous system lesions").

PROPHYLAXIS — Patients seropositive for T. gondii should receive prophylaxis according to the guidelines of the Centers for Disease Control and Prevention (CDC), United States Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA).

Primary prophylaxis — Prophylaxis is indicated for patients with HIV and CD4 counts <100 cells/µL who are T. gondii IgG positive. Patients who have negative toxoplasma serology should be counseled to avoid eating undercooked meats and to use gloves when carefully cleaning cat litter boxes. They do not need to avoid contact with household cats entirely.

Secondary prophylaxis — As noted above in the treatment section, following six weeks of therapy, patients can receive lower doses of drugs which is considered secondary prophylaxis or chronic suppressive therapy.

Sulfadiazine (2 to 4 g daily in 4 divided doses) plus pyrimethamine (25 to 50 mg daily) is the first choice for secondary prophylaxis. Folinic acid (10 mg to 25 mg daily) is also given concurrently.

Alternative regimens include: Clindamycin (300 mg PO QID or 450 mg PO TID) plus pyrimethamine (25 to 50 mg daily) plus folinic acid (10 to 25 mg daily. Atovaquone 750 mg PO 2 to 4 times daily with or without pyrimethamine 25 mg PO daily plus folinic acid 10 mg PO daily.

Atovaquone monotherapy 750 mg four times daily can be considered for patients who cannot tolerate pyrimethamine but the one year relapse rate is 26 percent.

Toxoplasmosis prophylaxis and immune reconstitution — If the CD4 count rises above 200 cells/µL for three months, primary prophylaxis for both PCP and toxoplasmosis can be safely discontinued.

The issue of secondary prophylaxis is more complex. Patients appear to be at low risk for recurrence of TE if they have completed therapy, remain asymptomatic, and have a sustained increase in their CD4+ T lymphocyte counts greater than 200 cells for more than six months. The CDC/USPHS/IDSA guidelines state that if immune reconstitution is maintained for six months, then secondary prophylaxis for TE can be discontinued.

The clinician needs to remember that the number of patients who have been evaluated with this approach is limited and the patient should be educated about symptoms that should lead to a prompt medical evaluation. Primary or secondary prophylaxis should be re-initiated if the CD4+ T lymphocyte count declines to less than 200 cells/microL.

SUMMARY Seroprevalence to T. gondii depends upon the part of the world in which the patient was born and resided more than upon the patient's HIV status. Toxoplasma encephalitis is the most common presentation of toxoplasmosis as an OI among AIDS patients and occurs most commonly in those with a CD4 count <100 cells/µL. Prophylaxis against PCP and the widespread use of HAART in developed countries has greatly decreased the incidence of this infection. The diagnosis of toxoplasma encephalitis is usually made presumptively in an AIDS patient with CD4 count <100/µL, a positive T. gondii IgG antibody, no recent prophylaxis against toxoplasmosis, and multiple ring-enhancing lesions on brain imaging. Brain biopsy can yield the diagnosis in patients who don't meet the above criteria or whose lesions fail to respond to presumptive therapy. First-line therapies for cerebral toxoplasmosis include pyrimethamine plus sulfadiazine or pyrimethamine plus clindamycin. Alternatives include pyrimethamine plus azithromycin, pyrimethamine plus atovaquone, sulfadiazine plus atovaquone, or as a last resort TMP/SMX. Folinic acid must always accompany pyrimethamine therapy. Corticosteroids are often administered in conjunction with antibiotics in patients with signs of significant increased intracranial pressure. The doses of pyrimethamine/sulfadiazine or pyrimethamine/clindamycin are usually lowered for maintenance treatment after approximately six weeks of therapy. Primary prophylaxis against toxoplasmosis is usually given to patients with CD4 counts <200 cell/µL. TMP-SMX in the doses given for PCP prophylaxis is the usual choice to accomplish prevention of both OIs. Both primary and secondary prophylaxis (maintenance therapy) can be discontinued in patients who achieve immune reconstitution with HAART.

Comments

	The Toxo IgM (Axsym) was all the time negative in this case. The patient had no HIV.
	The causative cause of his rapid deterioration was the escalation of rapid increase in ICP, because the abscess was near the foramen of Monroe.