Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. Case presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4(+) T cells and higher percentage of activated CD4(+) T cells at HAART initiation. The percentage of memory CD4(+) T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8(+) T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)]info:eu-repo/semantics/publishedVersio

Contrasting Physiological Responses of Two Populations of the Razor Clam Tagelus dombeii with Different Histories of Exposure to Paralytic Shellfish Poisoning (PSP)

This study describes the physiological performance of two populations of the razor clam Tagelus dombeii from two geographic areas with different histories of exposure to paralytic shellfish poisoning (PSP) linked to the toxic dinoflagellate Alexandrium catenella. Clams from Melinka-Aysen, which are frequently exposed to PSP, were not affected by the presence of toxins in the diet. However, clams from Corral-Valdivia, which have never been exposed to PSP, exhibited significantly reduced filtration activity and absorption, affecting the energy allocated to scope for growth (SFG). Ammonia excretion and oxygen uptake were not affected significantly by the presence of A. catenella in the diet. Measurements of energy acquisition and expenditure were performed during a 12-day intoxication period. According to three-way repeated measure ANOVAs, the origin of the clams had a highly significant effect on all physiological variables, and the interaction between diet and origin was significant for the clearance and absorption rates and for the scope for growth. The scope for growth index showed similar positive values for both the toxic and non-toxic individuals from the Melinka-Aysen population. However, it was significantly reduced in individuals from Corral-Valdivia when exposed to the diet containing A. catenella. The absence of differences between the physiological response of the toxic and non-toxic clams from Melinka-Aysen may be related to the frequent presence of A. catenella in the environment, indicating that this bivalve does not suffer negative consequences from PSP. By contrast, A. catenella has a negative effect on the physiological performance, primarily on the energy gained from the environment, on T. dombeii from Corral-Valdivia. This study supports the hypothesis that the history of PSP exposure plays an important role in the physiological performance and fitness of filter feeding bivalves

<i>Tagelus dombeii</i>.

<p>Clearance rate measured for a period of 12 days in individuals with different histories of exposure to PSP and exposed to toxic and non-toxic diets (3 replicates per experimental group at each sampling time). A, Melinka, Aysén (with previous PSP exposure); B, Corral, Valdivia (without previous PSP exposure).</p

<i>Tagelus dombeii</i>.

<p>Scope for growth measured for a period of 12 days in individuals with different histories of exposure to PSP and exposed to toxic and non-toxic diets (3 replicates per experimental group at each sampling time). A, Melinka, Aysén (with previous PSP exposure); B, Corral, Valdivia (without previous PSP exposure).</p

Three-way repeated-measures ANOVA for clearance rate, absorption rate, ammonia excretion, oxygen uptake and scope for growth in the razor clam <i>Tagelus dombeii</i>. TE = Time exposure.

<p>* p<0.05.</p><p>** p<0.01.</p><p>*** p<0.001.</p

Two-way repeated-measures ANOVA for clearance rate, ammonia excretion, oxygen uptake and scope for growth in the razor clam <i>Tagelus dombeii</i>. TE = time of exposure.

<p>* <i>p</i><0.05.</p><p>** <i>p</i><0.01.</p><p>*** <i>p</i><0.001.</p

<i>Tagelus dombeii</i>.

<p>Oxygen uptake measured for a period of 12 days in individuals with different histories of exposure to PSP and exposed to toxic and non-toxic diets (3 replicates per experimental group at each sampling time). A, Melinka, Aysén (with previous PSP exposure); B, Corral, Valdivia (without previous PSP exposure).</p

<i>Tagelus dombeii</i>.

<p>Clearance rate measured on <i>Alexandrium catenella</i> cells for a period of 12 days in individuals with different histories of exposure to PSP. A, Melinka, Aysén (with previous PSP exposure); B, Corral, Valdivia (without previous PSP exposure).</p

Characterization of toxic and non-toxic diets supplied to the razor clam <i>Tagelus dombeii</i>.

<p>Characterization of toxic and non-toxic diets supplied to the razor clam <i>Tagelus dombeii</i>.</p