Cerebral toxoplasmosis with neurological co-infection in people living with AIDS/HIV: results of a prospective cohort in São Paulo, Brazil.

BACKGROUND: Concomitant neurological diseases in people living with HIV/AIDS (PLWHA) is a challenging subject that has been insufficiently evaluated by prospective clinical studies. The goal of the present study was to identify the clinical characteristics and outcomes of PLWHA with cerebral toxoplasmosis and neurological co-infections. METHODS: We conducted a prospective observational cohort study at a tertiary teaching center in São Paulo, Brazil, from January to July 2017. Hospitalized PLWHA aged ≥ 18 years with cerebral toxoplasmosis were consecutively enrolled. A standardized neurological examination was performed at admission and weekly until discharge or death. Diagnosis and treatment followed institutional routines; neuroradiology, molecular diagnosis, neurosurgery, and the intensive care unit (ICU) were available. The main outcomes were neurological coinfections and in-hospital death. RESULTS: We included 44 (4.3%) cases among 1,032 hospitalized patients. The median age was 44 (interquartile range [IQR]: 35-50) years, and 50% (n = 22) of the patients were male. The median CD4+ T lymphocyte count was of 50 (IQR: 15-94) cells/mm3. Multiple lesions on computed tomography were present in 59% of the cases. Neurological coinfections were diagnosed in 20% (n = 9) of the cases, and cytomegalovirus was the most common etiology (encephalitis: n = 3; polyradiculopathy: n = 2). Longer hospital stays (30 versus 62 days; p = 0.021) and a higher rate of ICU admissions (14% versus 44%; p = 0.045) were observed among PLWHA with neurological coinfections in comparison to those without them. The rate of in-hospital mortality was of 13.6% (n = 6) (coinfection group: 33%; no coinfection group: 8.6%; p = 0.054). CONCLUSION: Neurological c-infections were common among PLWHA with cerebral toxoplasmosis, and cytomegalovirus was the main copathogen. The group of PLWHA with neurological co-infections underwent longer hospital stays and more frequent intensive care unit admissions. Additionally, this group of patients tended to have higher in-hospital mortality rate.

ANTECEDENTES: Coinfecções neurológicas em pessoas que vivem com HIV/AIDS (PVHA) é um tema que não foi suficientemente avaliado em estudos clínicos prospectivos. Nosso objetivo foi identificar as características clínicas e os desfechos de PVHA com toxoplasmose cerebral e coinfecções neurológicas. MéTODOS: Estudo prospectivo de coorte observacional conduzido em um centro de ensino terciário de São Paulo, Brasil, entre janeiro e julho de 2017. Foram incluídos consecutivamente PVHA internadas com ≥ 18 anos e toxoplasmose cerebral. Realizou-se exame neurológico padronizado na admissão e semanalmente até a alta/óbito. Tanto o diagnóstico quanto o tratamento seguiram a rotina institucional; neurorradiologia, diagnóstico molecular, neurocirurgia e Unidade de Terapia Intensiva (UTI) estavam disponíveis. Os principais desfechos foram coinfecções neurológicas e óbitos hospitalares. RESULTADOS: Incluímos 44 (4,3%) casos entre 1.032 pacientes internados. A idade mediana foi de 44 (intervalo interquartil [IIQ]: : 35­50) anos, e 50% (n = 22) dos pacientes eram do sexo masculino. A contagem mediana de linfócitos T CD4+ foi de 50 (IIQ:15­94) células/mm3. Múltiplas lesões na tomografia computadorizada foram observadas em 59% dos casos. Coinfecções neurológicas foram diagnosticadas em 20% (n = 9) dos casos, sendo o citomegalovírus a etiologia mais comum (encefalite: n = 3; polirradiculopatia: n = 2). Observou-se maior tempo de internação (26 versus 62 dias; p = 0,021) e uma taxa mais alta de admissão à UTI (14% versus 44%; p = 0,045) em PVHA com coinfecções neurológicas em comparação àquelas sem coinfecção. A mortalidade intra-hospitalar foi de 13,6% (n = 6) (grupo com coinfecções: 33% versus grupo sem coinfecção: 8,6%; p = 0,054). CONCLUSãO: Coinfecções neurológicas foram comuns em PVHA com toxoplasmose cerebral, sendo o citomegalovírus o principal copatógeno. O grupo de PVHA com coinfecções neurológicas apresentou maior tempo de internação, maior taxa de internações na UTI, e tendência a maior taxa de mortalidade intra-hospitalar.

Cerebral toxoplasmosis in HIV-infected patients: a review.

Toxoplasma gondii infection in the central nervous system commonly occurs among immunodeficient patients. Its prevalence is high in countries with a high burden of HIV and low coverage of antiretroviral drugs. The brain is one of the predilections for T. gondii infection due to its low inflammatory reaction, and cerebral toxoplasmosis occurs solely due to the reactivation of a latent infection rather than a new infection. Several immune elements have recently been recognized to have an essential role in the immunopathogenesis of cerebral toxoplasmosis. Although real-time isothermal amplification, next-generation sequencing, and enzyme-linked aptamer assays from blood samples have been the recommended diagnostic tools in some in-vivo studies, a combination of clinical symptoms, serology examination, and neuroimaging are still the daily standard for the presumptive diagnosis of cerebral toxoplasmosis and early anti-toxoplasma administration. Clinical trials are needed to find a new therapy that is less likely to affect folate synthesis, have neuroprotective properties, or cure the latent phase of infection. The development of a vaccine is being extensively tested in animals, but its efficacy and safety for humans are still not proven.

La clínica en el diagnóstico de la neurotoxoplasmosis / Clinic in the diagnosis of neurotoxoplasmosis

RESUMEN La toxoplasmosis cerebral o neurotoxoplasmosis es una de las infecciones oportunistas más frecuentes en los pacientes positivos al VIH. Se produce aproximadamente en el 10 % de los pacientes con sida no tratados. La localización de la infección, causada por el parásito Toxoplasma gondii, indica inmunodeficiencia severa, con linfocitos T CD4+ menor a 100 cel/mm3. El objetivo de este trabajo fue describir la evolución clínica e imagenológica de un paciente con diagnóstico de neurotoxoplasmosis, atendido en el Hospital Militar Dr. Carlos J. Finlay: hombre de 33 años, con síntomas neurológicos focales, sin factor de riesgo vascular, con estudios de imagen sugestiva de proceso expansivo intracraneal. Durante su ingreso se recibe el resultado de positivo al VIH y se interpreta como una neurotoxoplasmosis. Se empleó tratamiento antiparasitario con mejoría del trastorno neurológico y de las neuroimágenes. Ante un paciente con VIH y síntomas neurológicos focales se debe pensar en una neurotoxoplasmosis. La respuesta al tratamiento en el caso estudiado confirmó el diagnóstico (AU).

ABSTRACT Cerebral toxoplasmosis or neurotoxoplasmosis is one of the most common opportunistic infections in HIV-positive patients. It occurs in approximately 10 % of untreated AIDS patients. The location of the infection, caused by the parasite Toxoplasma gondii, indicates severe immunodeficiency, with CD4+ T lymphocytes less than 100 cell/mm3. The objective of this work was to describe the clinical and imaging evolution of a patient with diagnosis of neurotoxoplasmosis, attended at the Military Hospital Dr. Carlos J. Finlay: 33-year-old man, with focal neurological symptoms, without vascular risk factor, with studies of suggestive imaging of intracranial expansive process. During admission, the HIV positive result is received and interpreted as a neurotoxoplasmosis. Antiparasitic treatment was used with improvement of neurological disorder and neuroimagens. In the case of a patient with HIV and focal neurological symptoms doctors should think about neurotoxoplasmosis. The response to treatment in the case studied confirmed the diagnosis (AU).

Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living With Human Immunodeficiency Virus (HIV).

BACKGROUND: Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst matrix antigen 1 (MAG1), for predicting incident toxoplasmic encephalitis (TE) in people living with human immunodeficiency virus (HIV; PLWH). METHODS: We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in enzyme-linked immunosorbent assay (ELISA). RESULTS: Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. CONCLUSIONS: Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.

Development of a risk scoring system for prognostication in HIV-related toxoplasma encephalitis.

BACKGROUND: This study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them. METHODS: This is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing. RESULTS: In this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of '9' was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p < 0.001). The sensitivity and specificity of the risk scoring model was 100.0 and 86.9%, respectively, which were 81.8 and 94.1% of this scoring model in the verification cohort, respectively. CONCLUSIONS: The developed scoring system was established with simple risk factors, which also allows expeditious implementation of accurate prognostication, and appropriate therapeutic interventions in HIV-infected patients with TE.

What is AIDS in the Amazon and the Guianas in the 90-90-90 era?

INTRODUCTION: In the past decade, new diagnostic methods and strategies have appeared, HIV testing efforts and the generalization of antiretroviral therapy may have influenced the number of opportunistic diagnoses and mortality of HIV-infected patients. To test this hypothesis we compiled data on the top opportunistic infections and causes of early death in the HIV cohort of French Guiana. METHODS: HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals from 2010 to 2019 were studied. Annual incidence of different opportunistic infections and annual deaths are compiled. For patients with opportunistic infections we calculated the proportion of early deaths. RESULTS: At the time of analysis, among 2 459 patients, (treated and untreated) 90% had a viral load <400 copies, 91% of the patients in the cohort were on antiretroviral treatment, and 94.2% of patients on treatment for over 6 months had undetectable viral loads. Only 9% of patients had CD4 counts under 200 per mm3. Histoplasmosis clearly remained the most frequent (128 cases) opportunistic infection among HIV-infected persons followed by cerebral toxoplasmosis (63 cases) and esophageal candidiasis (41 cases). Cryptococcal meningitis was ranked 5th most frequent opportunistic infection as was tuberculosis (31 cases). The trend for a sharp decline in early deaths continued (3.9% of patients). CONCLUSIONS: Despite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress.

Chronic toxoplasmosis and sleepiness in obstructive sleep apnea: Is there a link?

INTRODUCTION: Sleepiness is the main clinical expression of obstructive sleep apnea (OSA) syndrome resulting from upper airway collapse. Recent studies have discussed the fact that the presence of T. gondii cysts in the brain and the resulting biochemical and immunological mechanisms could be linked to neurobehavioral disorders. The aim of the present study was to explore the potential impact of chronic toxoplasmosis on sleepiness and on obstructive sleep apnea (OSA) severity in OSA obese patients. MATERIALS AND METHODS: A case control study on obese patients screened for OSA was performed. According to the sleep disorder and matched based on gender, age and body mass index (BMI), two groups of obese patients were selected from our sample collection database. All patients were tested for toxoplasmosis serological status measuring anti-Toxoplasma IgG and IgM levels. Univariable and multivariable logistic regression models were performed to assess the impact of chronic toxoplasmosis on sleepiness and OSA severity. RESULTS: 107 obese patients suffering from OSA were included in the study (median age: 53.3 years Interquartile range (IQR): [41.9-59.9]; median BMI: 39.4 kg/m2 IQR: [35.5-44.1], apnea-hypopnea index = 27.5 events/h [10.7-49.9]). Chronic toxoplasmosis was present in 63.4% and 70.7% of patients with or without sleepiness (p = 0.48), respectively and was not associated either to sleepiness (OR: 0.76, 95% CI: [0.52; 2.33], p = 0.64) or OSA severity (OR = 1.75, 95% CI: [0.51; 5.98] p = 0.37). CONCLUSION: Although chronic Toxoplasma infection in immunocompetent humans has been associated to several behavioral disorders or pathologies in recent literature, we demonstrate here that chronic toxoplasmosis is not associated to sleepiness and to sleep apnea syndrome severity in obese patients suspected of sleep apnea syndrome.

Cerebral toxoplasmosis in HIV-infected patients over 2015-2018 (a case study of Russia).

Cerebral toxoplasmosis is a leading cause of the central nervous system disorders in acquired immune deficiency syndrome. This study aimed to investigate the clinical course of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected individuals. The study included 90 HIV-infected patients with cerebral toxoplasmosis, who underwent inpatient treatment. In case of positive enzyme immunoassay, HIV infection was confirmed with the immunoblot test. The HIV-1 ribonucleic acid level was determined using the polymerase chain reaction method. The flow cytometry was used for counting CD4 (cluster of differentiation 4 cells). Pathomorphological examination included the autopsy, gross and microscopic examination of internal organs, histological and other methods. The incidence of cerebral toxoplasmosis significantly increases at the CD4 count below 100 cells/µl, P < 0.001, and at the HIV viral load above 50 copies/ml, P < 0.05. The clinical picture of cerebral toxoplasmosis included focal symptoms, cognitive impairment, toxic syndrome, mild cerebral symptoms and a meningeal symptom. Given the absence of a specific clinical picture and the absence of abnormal laboratory and instrumental findings, the cerebral toxoplasmosis needs to be diagnosed with a number diagnostic methods combined: clinical examination, laboratory testing, immunological examination, molecular genetic testing and neuroradiological imaging.

Endemicity of Toxoplasma infection and its associated risk factors in Cebu, Philippines.

Toxoplasma gondii is a single-celled intracellular apicomplexan parasite that causes toxoplasmosis. It is capable of infecting humans and nearly all warm-blooded animals including pigs, but cats are the only known definitive host. This ubiquitous zoonotic pathogen can cause abortion, stillbirth and fetal abnormalities, and has been associated with mental and behavioral changes in humans. Acute infection is potentially fatal in immunocompromised individuals. The present study aimed to assess the Toxoplasma seroprevalence in pigs, humans and cats after its initial reported detection in pigs about three decades ago in Cebu, Philippines. A total of 924 humans, 104 cats and 514 slaughter pigs were tested for antibodies against T. gondii using a commercial latex agglutination test. The results revealed positive detection rates of 26.3% (244/924) for humans, 42.3% (44/104) for cats and 13.4% (69/514) for slaughter pigs. Statistical analyses revealed that the area (P = 0.004), cat ownership (P = 0.020), the frequency of contact with cats (P < 0.0001) and consumption of street foods (P = 0.043) were significantly associated with seropositivity for T. gondii in humans. Meanwhile, the use of litter trays (P = 0.001) and contact with other animals (P = 0.007) were significantly associated with seropositivity in cats. The odds ratio for selected significant factors revealed that living in suburban areas (OR 1.66, 95% CI: 1.20-2.31), owning a cat (OR 1.482, 95% CI: 1.07-2.07) and eating street foods (OR 1.585, 95% CI: 1.01-2.48) were associated with an increased risk of T. gondii exposure in humans. In cats, the use of a litter tray (OR 4.5, 95% CI: 1.73-11.71) was associated with an increased risk of exposure. None of the profile parameters were found to be significantly associated with seropositivity in slaughter pigs (P > 0.05). This study is the first report of the serological detection of T. gondii in humans and cats in Cebu, Philippines, and the first assessment of the prevalence of the parasite in pigs in the area since its initial detection in 1982. This is also the first report documenting the seropositivity of T. gondii in pregnant women in the country. The confirmed seropositivity of T. gondii in Cebu, Philippines, in the present study implies the endemicity of toxoplasmosis in this area and highlights the need for routine testing and increased public awareness.

Patient and treatment pathways for toxoplasmosis in the United States: data analysis of the Vizient Health Systems Data from 2011 to 2017.

Toxoplasmosis causes substantial morbidity and mortality in the United States (US). Clinical manifestations to toxoplasmosis vary and there is limited information on incidence or treatment patterns in the US. Treatment pathways for pyrimethamine-based regimens and trimethoprim-sulfamethoxazole (TMP-SMX) for toxoplasmosis hospitalizations were investigated using the Vizient Health Systems inpatient and outpatient data. Between January 1st, 2011 and December 31st, 2017, 10,273 hospital visits from 4,736 unique patients received a primary or secondary ICD-9/ICD-10 diagnosis for toxoplasmosis. The projected annual hospital visits with a diagnosis of toxoplasmosis was 68,821, corresponding to a total annual incidence of 9,832 comprising ocular toxoplasmosis of 2,169, toxoplasmic encephalitis of 1,399, unspecified toxoplasmosis of 4,368, congenital toxoplasmosis of 381, multisystemic toxoplasmosis of 69 and other toxoplasmosis of 1,446. Only 16.3% of the study population received treatment with pyrimethamine-based regimens or TMP-SMX. Pyrimethamine-based regimens were used significantly more often than TMP-SMX in toxoplasmic encephalitis (88.7% vs 79.6%, p = 0.01), other toxoplasmosis (85.0% vs 79.2%, p = 0.04), and unspecified toxoplasmosis (87.6% vs 77.9%, p = 0.03) in hospitals with 300 beds or more. A significantly higher percentage of visits with TMP-SMX as first-line treatment switched to pyrimethamine-based regimens compared to visits initiated on pyrimethamine-based treatments (26.7% vs 4.1%, p < .001). Ocular toxoplasmosis patients receiving pyrimethamine-based therapy were more likely to be discharged home compared to TMP-SMC at rates of 72.4% and 55.2%, respectively. Our analysis of commercial insurance records suggest toxoplasmosis is undertreated. Overall, pyrimethamine-based regimens are favored over TMP-SMX, have higher rates of discharge home, and have lower switch rates.

Congenital toxoplasmosis: An overview of the neurological and ocular manifestations.

Toxoplasma gondii is an obligate intracellular parasite which is known to infect one-third of the total world population chronically though it is asymptomatic in immunocompetent patients. However, in an immunocompromised patient or an infected fetus, it may cause devastating effects. The parasite may cross the placenta of an infected pregnant woman and probably infect the fetus congenitally. The severity of the infection depends on the gestational age at which the infection has occurred i.e., if it has occurred in the early phase, the rate of transmission is low but the severity is high if the fetus is infected and if it has occurred in the later phase then transmission rate is higher while the severity would be low. Congenital toxoplasmosis may result in non-specific consequences like abortion, intra-uterine growth restriction, jaundice, hepatosplenomegaly or even intra-uterine death. It may also result in neurological or ocular manifestations like intracranial calcifications, hydrocephalus or retinochoroiditis. The diagnosis may be done by serological screening of anti-Toxoplasma antibodies (IgM and IgG) while PCR of the amniotic fluid or the placenta is the confirmatory test. Acute or chronic infections may be differentiated by IgG avidity tests. The treatment regimens include spiramycin to prevent congenital transmission from an infected mother, pyrimethamine, sulfadoxine and folinic acid to treat the infected fetus, CSF shunting for the treatment of hydrocephalus and a combination of pyrimethamine, azithromycin, and corticosteroids for treating ocular toxoplasmosis.

Prevalence of cerebral toxoplasmosis among slaughtered sheep in Semnan, Iran

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. Felids are definitive hosts and all warm-blooded animals can be intermediate hosts. Some animals such as sheep, goats and pigs are sensitive to infection. In sheep production systems, toxoplamosis can cause abortion and economic loss. In public health, this disease can be transmitted to humans by the consumption of undercooked infected meat or other organs. In this study, T. gondii DNA was detected by B1 gene amplification in 140 randomly-selected brains of slaughtered sheep in Semnan, Iran. The prevalence of ovine cerebral toxoplasmosis was estimated using 95% confidence interval. The brain was selected as a target organ because it gives the highest detection rates, and the results can be compared with previous data from other countries. Our findings indicate that T. gondii is present in ovine tissues and can be passed on to humans by consuming undercooked or raw meat and other organs such as the liver. The infection can be lethal for immunosuppressed individuals and can cause abortion or birth of infected children in pregnant woman.

Central nervous system infection with Toxoplasma gondii.

Central nervous system infection by Toxoplasma gondii, or Toxoplasma encephalitis, is the most common cause of brain mass lesions in human immunodeficiency virus (HIV)-infected patients. It usually presents as one or more brain abscesses, but it can also cause a diffuse encephalitis or ventriculitis. Individuals who are Toxoplasma immunoglobulin G-seropositive, who have peripheral blood CD4+ T-cell concentrations below 200/µL, are not on antiretroviral therapy, and are not taking trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia, are at particular risk for Toxoplasma encephalitis. Neuroimaging typically shows round, isodense or hyperdense lesions in the hemispheric gray-white junction, deep white matter, or basal ganglia that enhance with contrast in a ring, nodular, or homogeneous pattern. In appropriate patients, response to an empiric treatment trial can establish the diagnosis. Immune reconstitution inflammatory syndrome is uncommon in HIV-infected patients treated for Toxoplasma encephalitis and combination antiretroviral therapy is an integral part of toxoplasmosis treatment.

Impact of alternative treatment approach for cerebral toxoplasmosis among HIV/AIDS patients from a resource-poor setting in Burkina Faso

Cerebral toxoplasmosis is caused by the protozoan Toxoplasma gondii because of reactivation of latent tissue cysts in the Acquired Immunodeficiency Syndrome (AIDS) patients with severe immunosuppression. The objective of this study was to evaluate the benefit of co-trimoxazole in presumptive and prevention of cerebral toxoplasmosis in Human Immunodeficiency Virus (HIV)/AIDS patients at Bobo-Dioulasso Hospital in Burkina Faso from June 2012 to October 2014. ELISA and ELFA were performed on serum for the quantitative determination of IgG and IgM anti-T. gondii, respectively. The seroprevalence of toxoplasmosis was 29.3%. No IgM antibodies for T. gondii were found. Six patients with Toxoplasma-specific antibodies presented cerebral toxoplasmosis. All patients were infected by HIV-1 with the median of CD4+ T lymphocytes at 141 cells/µl. No patient was under antiretroviral therapy. No case of cerebral toxoplasmosis was noted in patients receiving co-trimoxazole in prevention. Presumptive treatment of cerebral toxoplasmosis with co-trimoxazole was effective in all patients with a significant clinical improvement in 83.3%. These results attest the benefit of cotrimoxazole in cerebral toxoplasmosis treatment in countries where drug resources are limited when sulfadiazine is not available. Ours finding highlight the importance of establishing toxoplasmosis chemoprophylaxis to HIV with severe immunosuppression patients and positive Toxoplasma serology.

[Not everything is Zika: congenital toxoplasmosis, still prevalent in Colombia?] / No todo es Zika: toxoplasmosis congénita, ¿aún prevalente en Colombia?

Congenital toxoplasmosis continues to be a public health threat. Even existing guidelines, publicly known, its implementation and lack of appropriate interpretation of serological tests in pregnancy is often observed. This leds to failure in opportunities for positive and known interventions to decrease the fetal risk due to Toxoplasma gondii infection. We reported herein a case series, with variable neurological and systemic compromise (respiratory distress, hepatosplenomegaly, enterocolitis, brain calcifications, thrombocytopenia, ascites, shock), even fatal, calling for awareness about the fact that despite the Zika epidemics in 2015-2016 in Brazil, Colombia and other countries, precisely toxoplasmosis, is a differential diagnosis still prevalent in these territories, that can leds to severe consequences, with neurological disability and risk of ocular damage, even lately. Additionally, with varieties of T. gondii with more aggressive patterns in Latin America, which make worse those cases, including also a higher risk of death.

La toxoplasmosis congénita continúa siendo un problema de salud pública. Aun existiendo guías plenamente divulgadas y conocidas, se observa poca implementación de las mismas y falta de adecuada interpretación de pruebas serológicas en gestantes Esto puede generar falta de captación y tratamiento en embarazadas con primoinfección por Toxoplasma gondii. Reportamos una serie de casos, con compromiso neurológico y sistémico (dificultad respiratoria, hepatoesplenomegalia, enterocolitis, calcificaciones cerebrales, trombocitopenia, corioretinis, ascitis, choque). Si bien el virus de Zika causó epidemia en 2015-2016 en Brasil, Colombia y otros países, toxoplasmosis es un diagnóstico diferencial aún prevalente en estos países, con secuelas graves, discapacidad neurológica y riesgo de daño ocular, incluso tardío. Adicionalmente, existen algunas variedades de cepas de T. gondii con comportamiento más agresivo en Latinoamérica, lo cual empeora la presentación de los casos, incluyendo además mayor riesgo de muerte.

Relationship between toxoplasmosis and schizophrenia: A review.

A growing body of evidence suggests a correlation between schizophrenia and exposure to infectious agents. The majority of studied cases concerns the infection caused by T. gondii, an obligatory intracellular parasite that infects about 1/3 of the entire human population, according to the available data. The acute stage of the disease, predominantly short-lived and transient, transforms into the latent and chronic phase in which the parasite localizes within tissue cysts, mainly in the central nervous system. The chronic toxoplasmosis, primarily regarded as benign and asymptomatic, might be responsible, in light of current scientific evidence, for a vast array of neuropsychiatric symptoms. Numerous epidemiological case-control studies show a higher prevalence of T. gondii infestation in individuals with various psychiatric and behavior disorders, including schizophrenia. This paper tends to review the relevant studies that demonstrate links between schizophrenia and T. gondii infestation, of which the latter may be acquired in different developmental phases. Apart from epidemiological correlation studies, some papers on other associations were also presented, describing putative patophysiological mechanisms that might be at least partly responsible for chronic infection-induced neuromediator disturbances, together with morphological and functional alterations, e.g., low-grade neuroinflammation, which are likely to induce psychopathological symptoms. Toxoplasmosis is only one of the putative infectious agents that derange correct brain growth and differentiation, alongside genetic and environmental factors. All of them may lead eventually to schizophrenia. A better knowledge of infection mechanisms and its influence on neurobiochemical and neuropathological pathways may enable more efficient therapy and the prevention of this devastating disease.

Incidence, presentation and outcome of toxoplasmosis in HIV infected in the combination antiretroviral therapy era.

BACKGROUND: HIV-associated incidence and prognosis of cerebral toxoplasmosis (CTX) is not well established during later years. METHODS: From the Danish HIV Cohort Study, we identified 6325 HIV-infected individuals. We assessed incidence, mortality, predictive and prognostic factors of CTX during the pre-combination antiretroviral therapy (pre-cART; 1995-1996) and cART-era (1997-2014). Adjusted incidence rate ratios (aIRR), mortality rate ratios (aMRR) and 95% confidence intervals (CI) were assessed using Poisson regression analysis. RESULTS: CTX IR was 1.17/1000 PYR (95% CI 0.93-1.47). We observed no change in CTX-risk in the first year after HIV-diagnosis, but a substantial reduction in mortality in the first 3 months after CTX diagnosis when comparing the cART-era to the pre-cART-era; {(aIRR: 0.79; 95% CI: 0.37-1.72) (aMRR: 0.15; 95% CI: 0.06-0.38)}. For individuals surviving the first year after HIV-diagnosis or the first 3 months after CTX-diagnosis, IRR and MRR had declined to minimal levels {(aIRR: 0.06; 95% CI: 0.03-0.10); (aMRR: 0.02; 95% CI: 0.01-0.05)}. Three years after CTX-diagnosis 30% of the patients still had neurological deficits. CONCLUSION: Although, CTX remains an important cause of morbidity and mortality in the cART-era, with high prevalence of neurological sequelae, incidence and mortality has largely declined, especially among those surviving the first year after diagnosis.

No todo es Zika: toxoplasmosis congénita, ¿aún prevalente en Colombia? / Not everything is Zika: congenital toxoplasmosis, still prevalent in Colombia?

RESUMEN La toxoplasmosis congénita continúa siendo un problema de salud pública. Aun existiendo guías plenamente divulgadas y conocidas, se observa poca implementación de las mismas y falta de adecuada interpretación de pruebas serológicas en gestantes Esto puede generar falta de captación y tratamiento en embarazadas con primoinfección por Toxoplasma gondii. Reportamos una serie de casos, con compromiso neurológico y sistémico (dificultad respiratoria, hepatoesplenomegalia, enterocolitis, calcificaciones cerebrales, trombocitopenia, corioretinis, ascitis, choque). Si bien el virus de Zika causó epidemia en 2015-2016 en Brasil, Colombia y otros países, toxoplasmosis es un diagnóstico diferencial aún prevalente en estos países, con secuelas graves, discapacidad neurológica y riesgo de daño ocular, incluso tardío. Adicionalmente, existen algunas variedades de cepas de T. gondii con comportamiento más agresivo en Latinoamérica, lo cual empeora la presentación de los casos, incluyendo además mayor riesgo de muerte.

ABSTRACT Congenital toxoplasmosis continues to be a public health threat. Even existing guidelines, publicly known, its implementation and lack of appropriate interpretation of serological tests in pregnancy is often observed. This leds to failure in opportunities for positive and known interventions to decrease the fetal risk due to Toxoplasma gondii infection. We reported herein a case series, with variable neurological and systemic compromise (respiratory distress, hepatosplenomegaly, enterocolitis, brain calcifications, thrombocytopenia, ascites, shock), even fatal, calling for awareness about the fact that despite the Zika epidemics in 2015-2016 in Brazil, Colombia and other countries, precisely toxoplasmosis, is a differential diagnosis still prevalent in these territories, that can leds to severe consequences, with neurological disability and risk of ocular damage, even lately. Additionally, with varieties of T. gondii with more aggressive patterns in Latin America, which make worse those cases, including also a higher risk of death.

High rates of cerebral toxoplasmosis in HIV patients presenting with meningitis in Accra, Ghana.

Background: Data on adult meningitis among patients infected with the human immunodeficiency virus (HIV) is scarce in western sub-Saharan Africa, including Ghana. Methods: HIV-infected adults with a provisional diagnosis of meningitis were consecutively enrolled, between August 2014 and January 2016. After patient data collection, cerebrospinal fluid (CSF) was obtained and evaluated for microbiological aetiologies, cell counts and biochemistry. Caregiver clinicians provided limited data for inpatients at the end-point of discharge or death. Results: Complete data sets from 84 patients were analysed (inpatients=63, outpatients=21). Median age was 40 years with 56% (47/84) being females. Only 30% (25/84) of the patients were on antiretroviral therapy (ART). CD4+ T-cell count was available for 81% (68/84) of patients and 61.9% (52/84) had counts below 150 cells/µL [median and interquartile range=56 (13.8-136)]. Microbiological aetiologies were detected in 60.7% (51/84) patients with the following distribution-Toxoplasmosis (25%), Epstein-Barr virus (28.6%), Cytomegalovirus and Cryptococcus (2.4%) each. Co-infection was identified in 20.7% (17/84) of the patients. Conclusion: Patients presenting with symptoms of meningitis had advanced HIV/AIDS, a quarter of whom had cerebral toxoplasmosis or infection with EBV. A high index of suspicion, laboratory exclusion of cryptococcal meningitis and prompt patient management with anti-toxoplasmosis empiric therapy may thus be required for optimal treatment.

Effects of Cumulative Herpesviridae and Toxoplasma gondii Infections on Cognitive Function in Healthy, Bipolar, and Schizophrenia Subjects.

OBJECTIVE: Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls. METHODS: Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test). RESULTS: Seropositivity to and antibody levels of HSV-1 were significantly associated with working memory, which persisted after correction (backward digit span: ß = -0.10 [0.05], χ² = 33.89, P = .0001) in the overall sample. This association was particularly strong in the control group (ß = -0.18 [0.08], P = .04, Z = -3.55, P = .0008; corrected P = .012). Further, cumulative exposure to HSV-1, HSV-2, and CMV viruses and T gondii parasite was also associated with lower scores on working memory as measured by backward digit span in the overall sample (Z = 2.86, P = .004; Z = 2.47, P = .01; and Z = 3.35, P = .01, respectively). CONCLUSIONS: Exposures to Herpesviridae and T gondii parasite seem to impact cognitive functioning. Because infections caused by Herpesviridae and/or T gondii parasite are quite common in the (general) population, assessing and confirming the cognitive impairment among those who have cumulative exposures is useful and of interest.