Recurrent Headache as the Main Symptom of Acquired Cerebral Toxoplasmosis in Nonhuman Immunodeficiency Virus-infected Subjects With no Lymphadenopathy

Abstract

Headache and/or migraine, a common problem in pediatrics and internal medicine, affect about 5% to 10% children and adolescents, and nearly 30% of middle-aged women. Headache is also one of the most common clinical manifestations of acquired Toxoplasma gondii infection of the central nervous system (CNS) in immunosuppressed subjects. We present 11 apparently nonhuman immunodeficiency virus-infected children aged 7 to 17 years (8 girls, 3 boys) and 1 adult woman with recurrent severe headaches in whom latent chronic CNS T. gondii infection not manifested by enlarged peripheral lymph nodes typical for toxoplasmosis, was found. In 7 patients, the mean serum IgG Toxoplasma antibodies concentration was 189 +/- 85 (SD) IU/mL (range 89 to 300 IU/mL), and in 5 other subjects, the indirect fluorescent antibody test titer ranged from 1:40 to 1:5120 IU/mL (n= <1:10 IU/mL). Some of the patients suffered also from atopic dermatitis (AD) and were exposed to cat and/or other pet allergens, associated with an increased IL-4 and decreased IFN-gamma production. These cytokine irregularities caused limited control of cerebral toxoplasmosis probably because IL-4 down-regulated both the production of IFN-gamma and its activity, and stimulated production of a low NO-producing population of monocytes, which allowed cysts rupture, increased parasite multiplication and finally reactivation of T. gondii infection. The immune studies performed in 4 subjects showed a decreased percentage of T lymphocytes, increased total number of lymphocytes B and serum IgM concentration, and impaired phagocytosis. In addition, few of them had also urinary tract diseases known to produce IL-6 that can mediate immunosuppressive functions, involving induction of the anti-inflammatory cytokine IL-10. These disturbances probably resulted from the host protective immune reactions associated with the chronic latent CNS T. gondii infection/inflammation. This is consistent with significantly lower enzyme indoleamine 2,3-dioxygenase (IDO) activity reported in atopic than in nonatopic individuals, and an important role that IDO and tryptophan degradation pathways plays in both, the host resistance to T. gondii infection and its reactivation. Analysis of literature information on the subjects with different types of headaches caused by foods, medications, and other substances, may suggest that their clinical symptoms and changes in laboratory data result at least in part from interference of these factors with dietary tryptophan biotransformation pathways. Several of these agents caused headache attacks through enhancing NO production via the conversion of arginine to citrulline and NO by the inducible nitric oxide synthase enzyme, which results in the high-output pathway of NO synthesis. This increased production of NO is, however, quickly down-regulated by NO itself because this biomolecule can directly inactivate NOS, may inhibit Ia expression on IFN-gamma-activated macrophages, which would limit antigen-presenting capability, and block T-cell proliferation, thus ...

The Importance of Toxoplasma Gondii Infection in Diseases Presenting With Headaches. Headaches and Aseptic Meningitis May Be Manifestations of the Jarisch-Herxheimer Reaction

“…The infected host must therefore elaborate effective immune defense mechanisms being under permanent tight control (Aliberti, 2005). It was reported, however, that in apparently immunocompetent non-HIVinfected subjects with no peripheral lymphadenopathy, chronic latent CT was manifesting mainly with severe headaches (Desguerre & Ponsot, 1993;Khan & Correa, 1997;Prandota, 1998;Prandota, 2006;Prandota, 2007;Prandota, Sikorska, Wołoszczuk, & Dzik, 1988;Triki & Couvreur, 1971;Vukmirovits, Juhasz, Janko, & Toth, 1985). Moreover, Kang, Choi, Shin, and Lee (2006) showed that in mice infected with T. gondii, two weeks administration of dexamethasone resulted in depression of type T H 1 immune responses, followed by an increase in the number of parasites in the brain (Casciotti, Ely, Williams, & Khan, 2002;Wang, Claflin, Kang, & Suzuki, 2005).…”

Mollaret Meningitis may be Caused by Reactivation of Latent Cerebral Toxoplasmosis

“…On the other hand, however, population data indicate also that female sex may be a risk factor for chronic frequent headache (Wiendels et al, 2006). Moreover, our recent study also showed that among apparently immunocompetent patients with recurrent severe headaches caused by the increased intracranial hypertension due to reactivation of latent CT, were seven females and only three males (Prandota, 2007). Naturally occurring sexual dimorphism has been implicated in the risk, progression and recovery from numerous neurological disorders that could result from estrogen wide range of effects modulating cytokine expression in the CNS coupled with gender differences of cytokine production (Członkowska, Ciesielska, Gromadzka, & Kurkowska-Jastrz ebska, 2005).…”

“…These pathologic changes, as well as a nonspecific fever, headaches, disturbances in mental status, and focal neurological deficits may be the only manifestations of CT (Sell et al, 2005). Moreover, recently we found that the recurrent severe headaches in non-HIV-infected apparently immunocompetent subjects were due to reactivation of latent CT (Prandota, 2007;Prandota, 2007a;Prandota, 2008). Other authors also described single cases of aseptic meningitis and/or evidence for the increased intracranial pressure caused by T. gondii in apparently immunocompetent hosts without underlying illness and risk factors (Triki & Couvreur, 1971;Vukmirovits, Juhasz, Janko, & Toth, 1985;Desguerre & Ponsot, 1993;Khan & Correa, 1997).…”

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

“…In addition, insulin sensitivity was found to be impaired in the patients with migraine as compared with normal individuals (P < 0.001) [817,818]. Therefore, its seems that there is a relationship between migraine/other types of headache and T1DM/T2DM, especially that many patients with recurrent headaches/migraine were found to be seropositive for T. gondii [819,820] and about two billion of people worldwide are chronically infected with the parasite.…”