Cerebral toxoplasmosis is a rare complication of systemic lupus erythematosus (SLE). An 18 year old male student, newly diagnosed to have SLE, developed neurological symptoms two days after completing intravenous methylprednisolone. Computed tomography (CT) scan showed features consistent with a diagnosis of probable cerebral toxoplasmosis. He responded dramatically to antitoxoplasma therapy. To our knowledge, this is the first case report in the literature that presents a newly diagnosed SLE patient who rapidly developed cerebral toxoplasmosis following administration of intravenous methylprednisolone. Our case illustrates that this drug is potentially fatal and the importance of differentiating cerebral infection from neuropsychiatric lupus.
Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 - 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.
The seroprevalence of toxoplasmosis among 505 of human immunodeficiency virus (HIV)/AIDS patients was 226 (44.8%; 95% CI 42.64-51.76): 27 (47.4%) and 199 (44.4%) showed Toxoplasma seropositivity with and without toxoplasmic encephalitis (TE), respectively (P <0.05). The majority of these patients were in the 25-34 age group (44 versus 39%), male (86 versus 76%), and Chinese (49 versus 53%), though no statistical significance was found between the two. Significant differences between these two groups were noted, however, in terms of marital status, occupation, and present address. The heterosexual exhibited the most frequent behavior at risk for HIV infection, and accounted for 51 and 59% of patients with and without TE, respectively. Only 17/260 (6.5%) and 1/137 (0.7%) of them later acquired TE after receiving primary chemoprophylaxis (cotrimoxazole) and antiretroviral therapy including HAART (P <0.05). Fifty-seven (11.3%) out of those 505 patients were diagnosed with AIDS-related TE. The most common clinical manifestation was headache (56%). The computed tomography scan findings showed most lesions to be multiple (96.4%), hypodense (66.7%), and in the parietal region (39.3%). Twenty-seven (47.4%) patients had chronic (latent) Toxoplasma infection as evidenced by seropositivity for anti-Toxoplasma (IgG) antibody. At the time of diagnosis, the range of CD4 cell count was from 0-239 with a median of 25 cells/cumm. We also found that a CD4 count of less than 100 cells/cumm was significantly associated with development of TE (P <0.05). Clinical outcomes showed that among those who survived, 21 (36.8%), 16 (28.1%), and 2 (3.5%) of patients had completed treatment, transferred out, and were lost to follow up, respectively. Unfortunately, 18 (31.6%) of the cases were officially pronounced dead. Overall, 7 (12.3%) patients were detected as recurrent TE in this study.
CNS toxoplasmosis presenting as hydrocephalus is a very rare entity. We present three cases of HIV positive patients whose brain imaging revealed hydrocephalus and who improved with anti toxoplasma medication along with intravenous steroids and did not require any CSF shunting procedures. The mechanism of hydrocephalus in CNS toxoplasmosis is usually due to compression of CSF outflow pathway by ring enhancing lesions but even in their absence hydrocephalus can be rarely seen due to ventriculitis. Hence in HIV positive patients with unexplained hydrocephalus CNS toxoplasmosis should be considered and such patients if started on treatment early have a good prognosis without requiring neurosurgical intervention.
A 31-year-old Malaysian man was presented with an episode of seizures by the roadside, after having been recently diagnosed as HIV positive accompanied with miliary tuberculosis. On physical examination, he was oriented to person, but not to time or place. There was no neck stiffness or papilloedema. The other systemic examination was unremarkable. Chest examination revealed crepitations at the upper zone of the right lung. After diagnosis suspicion, the case was confirmed as toxoplasma encephalitis by MRI and serological tests. Patient was treated with trimethoprim/sulfamethoxazole 480-2400 mg/day with folinic acid supplement for 60 days. Two months later, a repeat brain MRI showed resolution of the cerebral lesions.
Toxoplasma gondii is an intra-cellular parasite that infects humans through vertical and horizontal transmission. The cysts remain dormant in the brain of infected humans and can reactivate in immunocompromised hosts resulting in acute toxoplasmic encephalitis which may be fatal. We determined the onset and progression of brain cysts generation in a mouse model following acute toxoplasmosis as well as the ability of brain cysts to reactivate in vitro. Male Balb/c mice, (uninfected control group, n = 10) were infected orally (study group, n = 50) with 1000 tachyzoites of T. gondii (ME49 strain) and euthanized at 1, 2, 4, 8 and 16 weeks post infection. Brain tissue was harvested, homogenized, stained and the number of brain cysts counted. Aliquots of brain homogenate with cysts were cultured in vitro with confluent Vero cells and the number of cysts and tachyzoites counted after 1 week. Brain cysts but not tachyzoites were detected at week 2 post infection and reached a plateau by week 4. In vitro Vero cells culture showed similar pattern for cysts and tachyzoites and reactivation of cyst in vitro was not influenced by the age of the brain cysts.
Four hundred and six AIDS patients were recruited in this retrospective study. The seroprevalence of toxoplasmosis among 406 AIDS patients was 208 (51.2%). Their age ranged from 17 to 74 years with a median of 35 years. The majority of patients were males 172 (82.6%), Malays 99 (47.5%), single 109 (52.4%), unemployed 99 (47.6%) and heterosexual with commercial sex workers (CSW) 97 (46.6%) as the risk marker to HIV infection. Thirty-one (14.9%) of 208 AIDS-related toxoplasmosis were diagnosed as active toxoplasmic encephalitis. The most common clinical manifestation was headache (67.7%). The CT scan findings showed most lesions to be multiple (87.5%), hypodense (66.7%), and in frontal region (41.7%). Twenty-two (71%) patients had chronic (latent) Toxoplasma infection as evidenced by seropositivity for anti-Toxoplasma (IgG) antibody. They were statistically significant in the association between CD4 count and toxoplasmic encephalitis (P = 0.019; OR = 2.6; 95% CI = 1.14-6.02). After the initial six weeks of anti-TE therapy, relapsing toxoplasmic encephalitis was detected in 9.7% in this study.
Toxoplasmosis, caused by an intracellular protozoan parasite, Toxoplasma gondii, is widespread throughout the world. The disease is of major medical and veterinary importance, being a cause of congenital disease and abortion in humans and in domestic animals.[1] In addition, it has gained importance recently due to toxoplasma encephalitis in AIDS patients.[2] T. gondii was discovered 100 years ago. Its identification was rapidly followed by the recognition that it was a human pathogen. During the past 100 years, the spectrum of diseases caused by this ubiquitous pathogen has expanded to include both congenital and acute infections as well as the recognition of diseases caused by this pathogen in the immune-compromised host. Recent data on behavioural changes in animals due to chronic toxoplasmosis is leading to research on the effect of this pathogen on the behaviour of humans.[3] Experimental studies on T. gondii have resulted in it becoming a model organism for studies on host pathogen interactions. Integration of clinical and experimental data on T. gondii should continue to lead to important insights into improvements in diagnosis for clinical management and vaccine development for control of toxoplasmosis.
We retrospectively reviewed 419 HIV/AIDS patients in Hospital Kuala Lumpur from 1994 to 2001. In the male group, the age range was 20-74, with a mean age 37 years, while in the female group it was 17-63, with a mean age of 33 years. With regard to age group, it was found that the preponderant age group was 25-34 years. The majority of male subjects were Chinese (52.5%), single (56.3%), and unemployed (55.1%), whereas the females were Malay (42.3%), married (79.5%), and non-laborer (64.1%). Also, both groups resided in Kuala Lumpur and had heterosexual contact as the leading cause of HIV transmission. More than half of the patients had CD4 cell counts of <200 cells/cumm. We found that the acquisition of HIV infection via intravenous drug use (IDU) was directly related to the incidence of tuberculosis infection (P < 0.05). Further analysis showed HIV-related tuberculosis with IDU was also dependently correlated with occupational status (unemployed) (P < 0.05). The four main AIDS-defining diseases include tuberculosis (48%), Pneumocystis carinii pneumonia (13%), toxoplasmic encephalitis (11%), and cryptococcal meningitis (7%); in addition, 53% of these patients were found to have CD4 cell counts of less than 200 cells/cumm at the time of diagnosis.
Central to the progression of cerebral toxoplasmosis is the interaction of Toxoplasma gondii with the blood-brain barrier (BBB) endothelial cells. In the present work, we tested the hypothesis that inhibition of Wnt pathway signalling by the monovalent ionophore monensin reduces the growth of T. gondii infecting human brain microvascular endothelial cells (hBMECs) or microglial cells. The anti-parasitic effect of monensin (a Wnt signalling inhibitor) on the in vitro growth of T. gondii tachyzoites was investigated using two methods (Sulforhodamine B staining and microscopic parasite counting). The monensin inhibited T. gondii growth (50% inhibitory concentration [IC50] = 0.61 μM) with a selective index = 8.48 when tested against hBMECs (50% cytotoxic concentration [CC50] = 5.17 μM). However, IC50 of monensin was 4.13 μM with a SI = 13.82 when tested against microglia cells (CC50 = 57.08 μM), suggesting less sensitivity of microglia cells to monensin treatment. The effect of T. gondii on the integrity of the BBB was assessed by the transendothelial electrical resistance (TEER) assay using an in vitro human BBB model. The results showed that T. gondii infection significantly decreased hBMECs' TEER resistance, which was rescued when cells were treated with 0.1 µM monensin, probably due to the anti-parasitic activity of monensin. We also investigated the host-targeted effects of 0.1 µM monensin on global gene expression in hBMECs with or without T. gondii infection. Treatment of hBMECs with monensin did not significantly influence the expression of genes involved in the Wnt signalling pathway, suggesting that although inhibition of the Wnt signalling pathway did not play a significant role in T. gondii infection of hBMECs, monensin was still effective in limiting the growth of T. gondii. On the contrary, monensin treatment downregulated pathways related to steroids, cholesterol and protein biosynthesis and their transport between endoplasmic reticulum and Golgi apparatus, and deregulated pathways related to cell cycle and DNA synthesis and repair mechanisms. These results provide new insight into the host-modulatory effect of monensin during T. gondii infection, which merits further investigation.