Toxoplasmosis Among 38 751 Hematopoietic Stem-cell Transplant Recipients: A Systematic Review of Disease Prevalence and a Compilation of Imaging and Autopsy Findings.

BACKGROUND: Toxoplasmosis in hematopoietic stem-cell transplant (HSCT) recipients can be life threatening if not promptly diagnosed and treated. METHODS: We performed a systematic review (PubMed last search March 29, 2020) of toxoplasmosis among HSCT recipients and calculated the toxoplasmosis prevalence across studies. We also created a compilation list of brain imaging, chest imaging, and autopsy findings of toxoplasmosis among HSCT recipients. RESULTS: We identified 46 eligible studies (47 datasets) with 399 toxoplasmosis cases among 38 751 HSCT recipients. There was large heterogeneity in the reported toxoplasmosis prevalence across studies, thus formal meta-analysis was not attempted. The median toxoplasmosis prevalence among 38 751 HSCT recipients was 2.14% (range 0%-66.67%). Data on toxoplasmosis among at-risk R+HSCT recipients were more limited (25 studies; 2404 R+HSCT recipients [6.2% of all HSCT recipients]), although the median number of R+HSCT recipients was 56.79% across all HSCT recipients. The median toxoplasmosis prevalence across studies among 2404 R+HSCT was 7.51% (range 0%-80%) versus 0% (range 0%-1.23%) among 7438 R-HSCT. There were limited data to allow meaningful analyses of toxoplasmosis prevalence according to prophylaxis status of R+HSCT recipients. CONCLUSIONS: Toxoplasmosis prevalence among HSCT recipients is underestimated. The majority of studies report toxoplasmosis prevalence among all HSCT recipients rather than only among the at-risk R+HSCT recipients. In fact, the median toxoplasmosis prevalence among all R+//R- HSCT recipients is 3.5-fold lower compared with the prevalence among only the at-risk R+HSCT recipients and the median prevalence among R+HSCT recipients is 7.51-fold higher than among R-HSCT recipients. The imaging findings of toxoplasmosis among HSCT recipients can be atypical. High index of suspicion is needed in R+HSCT recipients with fever, pneumonia, or encephalitis.

Management of toxoplasmosis in transplant recipients: an update.

INTRODUCTION: Toxoplasmosis is a life-threatening parasitic disease for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The risk of toxoplasmosis in transplant patients mainly depends on the degree of immunosuppression, the tropism of Toxoplasma gondii for the grafted tissue, and the seroprevalence in the general population. Although transplant recipients with toxoplasmosis have a high mortality rate, there are neither well-defined recommendations nor a consensus for the management of this disease in these patients. Areas covered. This review focuses on the management of toxoplasmosis in transplant recipients and discusses the various strategies for diagnosis, prevention, treatment, and follow-up in clinical practice. The literature search was conducted on publications in English and French using the search terms 'Toxoplasma gondii,' 'organ transplant,' and 'transplant recipients.' Expert commentary. The diagnosis of toxoplasmosis has greatly improved over the last two decades, but it is still a fatal illness. Non-specificity of the symptoms, resulting in a delay before diagnosis, and therapeutic failure are the main causes of death. The development of active treatments against cysts is one of the current challenges that will considerably improve the management of toxoplasmosis in transplant recipients by clearing chronic infection to avoid T. gondii reactivation.

Immunological interaction between Giardia cyst extract and experimental toxoplasmosis.

Toxoplasmosis is mostly associated with other intestinal parasitic infections especially Giardia due to shared mode of peroral infection. Toxoplasma and Giardia induce a strong T-helper 1- immune response. Our aim was to induce a protective immune response that results in significant impact on intestinal and extra-intestinal phases of Toxoplasma infection. This study was conducted in experimental animals and assessment of Giardia cyst extract effect on Toxoplasma infection was investigated by histopathological examination of small intestine and brain, Toxoplasma cyst count and iNOS staining of the brain, measurement of IFN-γ and TGF-ß in intestinal tissues. Results showed that the brain Toxoplasma cyst number was decreased in mice infected with Toxoplasma then received Giardia cyst extract as compared to mice infected with Toxoplasma only. This effect was produced because Giardia cyst extract augmented the immune response to Toxoplasma infection as evidenced by severe inflammatory reaction in the intestinal and brain tissues, increased levels of IFN-γ and TGF-ß in intestinal tissues and strong iNOS staining of the brain. In conclusion, Giardia cyst extract generated a protective response against T. gondii infection. Therefore, Giardia antigen will be a suitable candidate for further researches as an immunomodulatory agent against Toxoplasma infection.

Síndrome de TORCH: Enfoque racional del diagnóstico y tratamiento pre y post natal: Recomendaciones del Comité Consultivo de Infecciones Neonatales Sociedad Chilena de Infectología, 2016 / TORCH Syndrome: Rational approach of pre and post natal diagnosis.: Recommendations of the Advisory Committee on Neonatal Infections. Sociedad Chilena de Infectología, 2016

Existen numerosas infecciones bacterianas, virales y parasitarias que pueden transmitirse desde la madre al feto o recién nacido (RN) y que significan un riesgo para él. El acrónimo TORCH se utiliza en forma universal para caracterizar a aquel feto o RN que presenta un cuadro clínico compatible con una infección congénita y que permite un enfrentamiento racional, tanto diagnóstico como terapéutico. El concepto tradicional de realizar un "test de TORCH" sin consideraciones específicas a cada paciente, hoy en día se considera no adecuado y ha sido reemplazado por exámenes específicos para patógenos específicos bajo circunstancias bien definidas. El presente documento revisa las características generales, epidemiológicas, patogénicas, diagnósticas y terapéuticas de los patógenos más frecuentemente involucrados en el estudio de pacientes con sospecha de TORCH.

There is a lot of bacterial, viral or parasite infections who are able to be transmitted vertically from the mother to the fetus or newborn which implicates an enormous risk for it. The TORCH acronym is used universally to refer to a fetus or newborn which presents clinical features compatible with a vertically acquired infection and allows a rational diagnostic and therapeutic approach. The traditional "TORCH test" is nowadays considered not appropriate and it has been replaced for specific test for specific pathogens under well defined circumstances. The present document reviews the general characteristics, epidemiology, pathogenesis, diagnostic and therapeutic options for the most frequently involved pathogens in the fetus or newborn with TORCH suspicion.

Efecto del tratamiento prenatal con espiramicina en la frecuencia de retinocoroiditis por toxoplasmosis congénita en una cohorte colombiana / Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort

Resumen Introducción. La toxoplasmosis de la gestación es frecuente y grave. Hasta ahora no hay consenso sobre la utilidad del tratamiento para prevenir complicaciones oculares en el neonato. En la actualidad, uno de los medicamentos utilizados en las madres diagnosticadas es la espiramicina oral. Infortunadamente, en algunas mujeres gestantes no se hace el diagnóstico prenatal y, por esta u otras razones, no reciben el tratamiento. Objetivo. Describir la relación entre el tratamiento con espiramicina durante el embarazo en madres con toxoplasmosis de la gestación y la presentación de toxoplasmosis ocular en los recién nacidos. Materiales y métodos. Se llevó a cabo un estudio observacional descriptivo de serie de casos. Se evaluó una serie prospectiva de pacientes con toxoplasmosis de la gestación durante tres años de seguimiento en el Servicio de Retinología de la Clínica Universitaria Bolivariana de Medellín. Resultados. Se registraron 23 madres con diagnóstico de toxoplasmosis de la gestación. Quince de ellas (65 %) recibieron durante la gestación tratamiento con espiramicina en dosis de 3 g al día; uno de los neonatos (6,6 %) presentó toxoplasmosis ocular. De las ocho (35 %) pacientes que no recibieron tratamiento, cinco (62,5 %) tuvieron hijos con compromiso ocular por toxoplasma. La razón de momios (odds ratio, OR) del efecto protector contra dicho compromiso en los pacientes cuyas madres recibieron tratamiento fue de 0,04 (IC95% 0,00-0,67), con valor de p menor de 0,01 en la prueba exacta de Fisher. Solo se evidenció compromiso del sistema nervioso central por toxoplasmosis mediante las imágenes de tomografía o ecografía cerebral en dos (14 %) pacientes de las 14 en quienes se hicieron estos estudios. Los dos pacientes presentaron, además, compromiso ocular; ambos fueron diagnosticados en el momento del nacimiento y sus madres no habían recibido tratamiento prenatal. Conclusiones. Estos resultados evidencian que el tratamiento con espiramicina durante el embarazo en la toxoplasmosis de la gestación redujo en 96 % (IC95% 33-100 %) el riesgo relativo de presentar la enfermedad en el recién nacido.

Abstrat Introduction: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. Objective: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. Materials and methods: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. Results: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. Conclusions: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Toxoplasmosis presented as a submental mass: a common disease, uncommon presentation.

Submental mass secondary to toxoplasmosis is not common in clinical work. A diagnosis of toxoplasmosis is rarely considered by physicians. Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. Diagnosis of toxoplasmosis was finally established by a combination of the pathological criteria, together with the positive serological finding. According to review the clinical presentations, pathological characteristics, diagnostic standard and treatment of this disease, the article aims to remind otolaryngologists who are evaluating a neck mass should be aware of the infectious cause of lymphadenopathy and the possibility of toxoplasmosis.

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

Adoptive transfer of Treg cells counters adverse effects of Toxoplasma gondii infection on pregnancy.

Acute infection with Toxoplasma gondii (T. gondii) during pregnancy is associated with adverse outcomes. The mechanisms that cause this phenomenon are not clear. Regulatory T cells (Tregs) are involved in maternal tolerance, and here we observed a decrease in the absolute numbers of CTLA-4(+) Tregs and PD-1(+) Tregs in spleen and at the fetal-maternal interface in T. gondii-infected mice. Our results suggest that T. gondii induces apoptosis of Tregs. Additionally, we found that the expression of CTLA-4 and PD-1 on Tregs at fetal-maternal interface were higher than on spleen cells from normal pregnant mice. Therefore, we adoptively transferred Tregs from fetal-maternal interface or from spleens of normal pregnant mice into infected pregnant mice. Pregnancy outcomes were improved when Tregs were transferred from the fetal-maternal interface but not from the spleen. The mechanism appears to be through up-regulation of the number of CTLA-4(+) Tregs and PD-1(+) Tregs and correction of the imbalance between tolerant cytokines (IL-10, TGF-ß) and inflammatory cytokines (IFN-γ). Our data indicate that Tregs at fetal-maternal interface express high levels of inhibitory molecules that play a vital immuno-protective role during pregnancy.

Toxoplasmose e Toxoplasma gondii / Toxoplasmosis and Toxoplasma gondii

A infecção por Toxoplasma gondii é hoje muito disseminada ao redor do mundo, especialmente no Brasil. A coletânea parte da história da descoberta desse parasita e da doença por ele causada, a toxoplasmose, e visita os diferentes aspectos relacionados ao tema. São apresentados o ciclo evolutivo, a epidemiologia, o diagnóstico, o quadro clínico e o tratamento, em uma ampla revisão sobre o assunto, provavelmente a mais completa já realizada. Somente nos anos 1970 desvendou-se o ciclo de vida desse protozoário, do qual o gato é hospedeiro definitivo. Outros animais de sangue quente, entre eles o ser humano, são hospedeiros intermediários. Muitos indivíduos infectados pelo T. gondii não apresentam sintomas, mas, quando a doença se manifesta, pode ter diferentes configurações, afetando gânglios, olhos, coração, pulmões, fígado, cérebro e meninges, ou articulações. Além de uma completa revisão, a obra também traz para o leitor o que há de mais atual no conhecimento científico acerca da toxoplasmose e do T. gondii. O livro cobre praticamente todos os campos do conhecimento sobre o agente etiológico e a doença, apresentando novos aspectos, particularmente em relação à bioquímica, à interação entre o parasita e a célula hospedeira e à resposta imunológica à infecção.

Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study.

BACKGROUND: Characteristics and outcomes of adult patients with disseminated toxoplasmosis admitted to the intensive care unit (ICU) have rarely been described. METHODS: We performed a retrospective study on consecutive adult patients with disseminated toxoplasmosis who were admitted from January 2002 through December 2012 to the ICUs of 14 university-affiliated hospitals in France. Disseminated toxoplasmosis was defined as microbiological or histological evidence of disease affecting >1 organ in immunosuppressed patients. Isolated cases of cerebral toxoplasmosis were excluded. Clinical data on admission and risk factors for 60-day mortality were collected. RESULTS: Thirty-eight patients were identified during the study period. Twenty-two (58%) had received an allogeneic hematopoietic stem cell transplant (median, 61 [interquartile range {IQR}, 43-175] days before ICU admission), 4 (10%) were solid organ transplant recipients, and 10 (27%) were infected with human immunodeficiency virus (median CD4 cell count, 14 [IQR, 6-33] cells/µL). The main indications for ICU admission were acute respiratory failure (89%) and shock (53%). The 60-day mortality rate was 82%. Allogeneic hematopoietic stem cell transplant (hazard ratio [HR] = 2.28; 95% confidence interval [CI], 1.05-5.35; P = .04) and systolic cardiac dysfunction (HR = 3.54; 95% CI, 1.60-8.10; P < .01) within 48 hours of ICU admission were associated with mortality. CONCLUSIONS: Severe disseminated toxoplasmosis leading to ICU admission has a poor prognosis. Recipients of allogeneic hematopoietic stem cell transplant appear to have the highest risk of mortality. We identified systolic cardiac dysfunction as a major determinant of outcome. Strategies aimed at preventing this fatal opportunistic infection may improve outcomes.

Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients.

Toxoplasmosis is a rare and possibly underestimated complication following hematopoietic stem cell transplantation (HSCT) associated with a high mortality rate, although the incidence of toxoplasmosis after HSCT in Japan has not been established. We retrospectively studied patients with toxoplasmosis after HSCT, and identified five patients who had been diagnosed with an acute exacerbation of toxoplasmosis among 279 HSCT recipients at our institution between 1998 and 2011, representing an incidence of 1.8 %. Among 87 autologous HSCT recipients, one definite case was diagnosed. The serological test for Toxoplasma gondii before HSCT was positive in 18 of 192 allogeneic HSCT recipients. Of the 18 seropositive patients, three had definite infections, and one had possible infection. All four definite cases were diagnosed at autopsy. In the definite cases, three allogeneic HSCT recipients had disseminated or pulmonary toxoplasmosis and one autologous HSCT recipient had toxoplasmic encephalitis, although toxoplasmosis was not suspected at the premortem examination due to non-specific clinical and radiological manifestations. Thus, acute exacerbation of toxoplasmosis should be suspected in recipients after HSCT. Early diagnosis and treatment for toxoplasmosis would certainly contribute to a decrease in mortality after HSCT.

Prevención de la toxoplasmosis congénita en un hospital de Buenos Aires / Prevention of congenital toxoplasmosis in a Buenos Aires hospital

La prevención de la toxoplasmosis congénita se basa en la información de la mujer con medidas de prevención primaria, el diagnóstico serológico y el tratamiento de la embarazada y del niño. Se presentan los resultados de 12 años de implementación de un programa de prevención de la toxoplasmosis congénita, la tasa de madres infectadas, de transmisión vertical, de niños infectados y la gravedad de la afección causada. Se realizó un estudio observacional prospectivo sobre 12 035 gestantes atendidas en la maternidad del Hospital Alemán de Buenos Aires entre enero de 2000 y diciembre de 2011. Se observó una prevalencia de anticuerpos anti Toxoplasma gondii de 18.33% (2 206/12 035). Treinta y siete mujeres de 9 792 susceptibles tuvieron infección aguda, la tasa de incidencia de infección materna fue de 3.78 por 1 000 nacimientos. La tasa de transmisión transplacentaria de la infección fue 5.4% (2/37). Dos recién nacidos tuvieron toxoplasmosis congénita, uno no tuvo signos clínicos y el otro presentó coriorretinitis y estrabismo. Recibieron tratamiento 35 madres y los 2 niños con toxoplasmosis congénita. En conclusión: Las cifras de transmisión obtenida permiten considerar a este programa de prevención como un recurso válido para minimizar el impacto de la toxoplasmosis congénita.

The prevention of congenital toxoplasmosis is based on providing information to women, serologic diagnosis and treatment of the infected mother and child. In this article we present the results of 12 years of implementation of a congenital toxoplasmosis prevention program in which we measured the mother´s infection incidence rate, the transmission rate and the number and severity of infection in newborns. The study was performed on 12 035 pregnant women in the period 2000-2011. The prevalence rate of antibodies against Toxoplasma gondii was 18.33% (2 206/12 035). Thirty-seven out of 9 792 susceptible women presented acute infection and the mother's infection incidence rate was 3.78 per 1000 births. The transplacental transmission rate was 5.4% (2/37). Two newborns presented congenital toxoplasmosis infection, one had no clinical signs while the other presented strabismus and chorioretinitis. Thirty-five infected mothers and the two children with congenital infection were treated. The transmission rates obtained allow consider this prevention program as a valid resource to minimize the impact of congenital toxoplasmosis.

Neurological complications associated with HIV and AIDS: clinical implications for nursing.

This article provides a clinical nursing update on major neurological complications associated with HIV and AIDS. Life expectancy for those with AIDS has increased as a consequence of antiretroviral therapy, and thus, neurological complications remain a clinical challenge. Four significant diseases associated with HIV and AIDS are addressed: HIV-associated dementia, peripheral neuropathy, cryptococcal meningitis, and toxoplasmosis. Updated statistics, a review of pathophysiology, common manifestations, diagnostic tests, and standard treatments are discussed for each disease. Nursing considerations when caring for this population are reviewed and include assessment, safety, activities of daily living, pain management, and treatment adherence.

[Pulmonary toxoplasmosis in immunosuppressed patient]. / Toxoplasmoza pulmonara la pacientul imunodeprimat.

Pulmonary toxoplasmosis occurs mainly in immunosuppressed patients and its diagnosis mainly relies upon biological confirmation of the parasite. We present the case of a 47 years patient in medullar aplasia after induction chemotherapy for acute lymphoblastic leukemia that developed pulmonary infiltrates of parasitic origin. The diagnosis of pulmonary toxoplasmosis was established after identification of the parasite in brochioloalveolar lavage fluid (BAL) and peripheral blood. Serological tests are of limited utility in immunosuppressed patients. We used classical methods for the diagnosis of parasitosis but they are being replaced by molecular methods. Polymerase Chain Reaction (PCR) allows a highly specific and sensitive diagnosis on any sample but it cannot be performed in any center.

The CD8 T-cell road to immunotherapy of toxoplasmosis.

Toxoplasma gondii infection induces a robust CD8 T-cell immunity that is critical for keeping chronic infection under control. In studies using animal models, it has been demonstrated that the absence of this response can compromise the host ability to keep chronic infection under check. Therapeutic agents that facilitate the induction and maintenance of CD8 T-cell response against the pathogen need to be developed. In the last decade, major strides in understanding the development of effector and memory response, particularly in viral and tumor models, have been made. However, factors involved in the generation of effector or memory response against T. gondii infection have not been extensively investigated. This information will be invaluable in designing immunotherapeutic regimens needed for combating this intracellular pathogen that poses a severe risk for pregnant women and immunocompromised individuals.