Toxoplasmosis Research Articles

Optimal Timing of Antiretroviral Therapy Initiation in Acquired Immunodeficiency Syndrome–Associated Toxoplasmic Encephalitis: A Prospective Observational Multicenter Study in China

Abstract Background Toxoplasmic encephalitis (TE) is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome (AIDS). However, the optimal timing of antiretroviral therapy (ART) initiation in these patients remains controversial. This study aims to investigate the differences in outcomes of ART initiation at different times, in order to help clarify the treatment timing of AIDS-associated TE. Methods This multicenter prospective observational study included 87 patients recruited from 11 research centers in China (from March 2019 to December 2022). Of the patients, 38 were assigned to the early ART group (initiating ART within 2 weeks after anti-Toxoplasma treatment initiation), and the remaining 49 patients received deferred ART (initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation). The main outcomes included mortality and emergence of immune reconstitution inflammatory syndrome (IRIS). Human immunodeficiency virus (HIV)-1 viral load and CD4+ T-cell counts at weeks 24 and 48 were observed. Results The number of deaths (1 vs. 5, P = 0.225) and incidence of IRIS (2.6% vs. 0, P = 0.437) were not significantly different between the early and deferred ART groups at week 48. Early ART initiation did not contribute significantly to HIV-1 viral load control (<50 copies/mL, n = 8 vs. n = 3 at week 24, P = 0.142; n = 7 vs. n = 7 at week 48, P = 1.000). The median CD4+ T-cell counts between the two groups were not significantly different, either at week 24 (155 vs. 91 cells/mm3, P = 0.837) or at week 48 (181 vs. 146 cells/mm3, P = 0.219). Conclusion In patients with AIDS-associated TE, early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality, IRIS, and HIV virological and immunological outcomes. Trial registration: This study was registered (registration number: ChiCTR1900021195) as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry (chictr.gov) on February 1, 2019. Enrollment for this study began in March 2019.

Biological screening for congenital toxoplasmosis in newborns from Jataí, Goiás, Brazil: a cross-sectional study.

To conduct a serological screening for toxoplasmosis in the heel prick test and to evaluate its epidemiological aspects in newborns and postpartum women in Jataí, Goiás. Cross-sectional epidemiological study for the biological screening of newborns in Jataí, Goiás. The study participants amounted to 228 newborns, whose samples were collected between the third and seventh day of life. IgG antibodies against Toxoplasma gondii were detected in 40.79% (93/228) of the samples; out of these, 23.6% (22/93) had high IgG antibody titers, leading to the collection of two other peripheral blood samples and the detection of a decrease in these titers. The findings show the importance of strengthening actions in primary health care to prevent infection and training health professionals in this area to equip them with information regarding cases of reinfection and reactivation of infection in pregnant women, minimizing risks for babies.

Current Status of Congenital Toxoplasmosis in Brazzaville, Republic of the Congo

Current Status of Congenital Toxoplasmosis in Brazzaville, Republic of the Congo

Sulfadiazine-induced crystalluria and non-oliguric renal failure in HIV-1 inaugural infection with presumed cerebral toxoplasmosis

Sulfadiazine-induced crystalluria and non-oliguric renal failure in HIV-1 inaugural infection with presumed cerebral toxoplasmosis

Seroprevalence of Toxoplasma gondii among Aborted Women Admitted to Erbil Maternity Teaching Hospital

Background: Toxoplasma gondii is an obligate intracellular parasite responsible for causing congenital toxoplasmosis. Congenital infection during the first and second trimesters of pregnancy may result in spontaneous abortion, mental retardation, and cerebral calcifications, while the severity of fetal damage is decreased during the third trimester.
 
 Objectives: This study aimed to determine the seroprevalence of toxoplasmosis and its association with clinical-obstetric determinants and sociodemographic factors in aborted women.
 
 Materials and Methods: The present study was a Hospital-based Cross-sectional Study comprised 100 women who admitted to Erbil Maternity Hospital with a spontaneous abortion. A questionnaire was filled by the researchers after verbal consent, and 5 ml of venous blood was collected from each participant, centrifuged at 3500 rpm, and stored in 2 Eppendorf tubes, and tested by ELISA and Electrochemiluminescence Immunoassay by Cobas e 411 for Toxoplasma IgG and IgM according to Manufacturer’s instructions.
 
 Results: The highest seroprevalence for toxoplasmosis was observed in illiterate females aged 26-35 and living in Erbil City's urban areas. A statistically significant association was recorded regarding seropositivity to Toxoplasma IgG and having a history of abnormal babies (P=0.023), Toxoplasma IgG seropositivity and a history of having toxoplasmosis (P=0.016), and seropositivity to Toxoplasma IgM and parity of the females (P=0.037).
 
 Conclusions: Screening for toxoplasmosis during pregnancy is crucial for all women for the prevention of disease progression. Although there are various screening methods for the detection of toxoplasmosis, not all the methods are applicable and financially suitable for the patients.

Evaluation of the Western Blot Densitometry for the Diagnosis of Congenital Toxoplasmosis

BACKGROUND: Congenital toxoplasmosis can cause severe ocular and neurological sequels such hydrocephaly, seizures, and chorioretinitis, leading to permanent visual deficit and multiple neurological deficits, if left untreated. An early diagnosis is crucial to prevent the development of these consequences and western blot is the most important diagnostic tool for this disease in newborns, because can distinguish between antibodies transferred from the mother or those produced by the newborn. However, the reading of the results still being done by subjective analysis by expert clinical laboratory specialists, reaching a maximum of 73% of sensitivity. The digitalization of the image of the results of western blot and its analysis by a software quantifying the densitometry of the bands obtained by western blot assay can potentially improve the diagnostic performance of the technique. METHODS: Was evaluated the sensitivity and specificity by digitalizing pictures of western blot results from the laboratory of Biomedical Research at the University of Quindío and published in the scientific literature. For the research, GelAnalyzer 19.1 software was used to digitalize the bands from western blot membranes from mother and child serum and the molecular weight of protein bands was calculated. The images were from 15 cases of newborns during the first month of life (six from our laboratory and nine from literature), and five negative controls (three from the laboratory and two from literature). Definition of true cases were the persistence of IgM/IgA after day 10 of life, mother with IgG and IgM antibodies positive and newborn with positive IgG plus symptoms, or no decrease in IgG in follow-up. The true negative cases were all newborn whose become negative for IgG anti Toxoplasma before the month 10 of life in absence of treatment, indicating that were maternal passively transferred antibodies. RESULTS: When comparing the immunological profiles of the mothers and their children for IgG by densitometry, congenital infections were detected in 80% (12 out of 15) of the cases (sensitivity) in serum samples obtained during the first month of life. All controls were negative (100% specificity). There was a percentage of 53% (8 out of 15) of children not identifiable with the visual analysis performed by two undergraduate researchers, likewise, the specificity with observation was 57% (3 out of 5) contrasted with the present study. Finally, three bands were identified as the most common in newborns with congenital infection: 49 KDa, 98-97 KDa and 72 KDa proteins (in order of frequency). CONCLUSION: Digitalization of western blot images increase sensitivity for the diagnosis of newborn with congenital toxoplasmosis during the first month of life.

Metanalysis of the Diagnostic Performance of Western Blot for the Early Diagnosis of Congenital Toxoplasmosis

BACKGROUND: Congenital toxoplasmosis is an infection caused by the Toxoplasma gondii a protozoa obligate intracellular parasite that appears after a mother´s primary infection occurs during pregnancy. The congenital infection can cause severe symptoms such as: hydrocephalus, intracranial calcifications, seizures, hepatosplenomegaly, and chorioretinitis, leading to irreversible neurological and ocular lesions. Its early diagnosis is critical to obtain good outcomes after treatment where the western blot is considered as the gold standard. Western blot discriminate antibodies for specific proteins of the microorganism enabling differentiation between antibodies transmitted by mother from those elaborated by the newborn (compared immunological profiles) and can be obtained commercially or be elaborated by the clinical laboratory test (“house made”). However, there is not metanalysis about the diagnostic properties of the test that can support evidence-based recommendations for its use. METHODS: The research terms used were: “congenital toxoplasmosis” and “western blot”. Databases for bibliographic searches were PubMed and Scopus, without restriction of date or language. Selection criteria were studies of evaluation of the diagnostic performance of western blot assay that included newborn with a definitive diagnosis of congenital infection by Toxoplasma according to the European network case definition (IgG anti-Toxoplasma persistent at 10 months of age) and controls that were defined by IgG antibodies that disappears in the serum of children in absence of treatment before six months of age. Screening and literature selection was done by the four researchers and disagreement were settled by reaching a consensus by discussion with mentor to avoid the erroneous exclusion of eligible articles. The PRISMA statement (http://www.prisma-statement.org/) was followed for quality assessment of the manuscript. The data were organized in an evidence table matrix, and sensitivity, specificity, and diagnostic odds ratio (DOR) index were calculated. RESULTS: Of 44 articles related to the search terms were found in literature databases, 10 fulfill criteria to be included in the metanalysis. The sensitivity obtained was 93.8 (95 CI: 79.2-98.4) and the specificity of 96.6% (95 CI: 89.8-98.9). However, heterogeneity was observed between the studies. Causes for heterogeneity were the different methods to elaborate the western blot assay. Commercial methods showed better performance that homemade methods. The results suggest that better accuracy can be obtained by using standardized commercial test. CONCLUSION: In conclusion, the meta-analysis supports the use of the Western Blot test as an effective method for the diagnosis of congenital toxoplasmosis in terms of sensitivity and specificity. However, further research is needed to establish more accuracy regarding sensitivity and specificity in the diagnosis in different settings by using well standardized assays.

A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis.

Toxoplasma gondii, an obligate intracellular eukaryotic parasite, can infect about one-third of the world's population. One vaccine, Toxovax, has been developed and licensed commercially; however, it is only used in the sheep industry to reduce the losses caused by congenital toxoplasmosis. Various other vaccine approaches have been explored, including excretory secretion antigen vaccines, subunit vaccines, epitope vaccines, and DNA vaccines. However, current research has not yet developed a safe and effective vaccine for T. gondii. Here, we generated an mRNA vaccine candidate against T. gondii. We investigated the efficacy of vaccination with a novel identified candidate, TGGT1_278620, in a mouse infection model. We screened T. gondii-derived protective antigens at the genome-wide level, combined them with mRNA-lipid nanoparticle vaccine technology against T. gondii, and investigated immune-related factors and mechanisms. Our findings might contribute to developing vaccines for immunizing humans and animals against T. gondii.

Hope remains: A case of toxoplasmic encephalitis in a 25-year-old immunocompromised host

Hope remains: A case of toxoplasmic encephalitis in a 25-year-old immunocompromised host

1622. Increase in Congenital Toxoplasmosis and Acute Toxoplasmosis Among Pregnant Women in the US during the COVID-19 pandemic

Abstract Background During the COVID19 pandemic a rise in diverse opportunistic infections has been described Methods In this retrospective cohort study, we analyzed the trajectory of new congenital toxoplasmosis (CT) cases and cases of acute toxoplasmosis among pregnant women (AT-P) during the COVID19-pandemic (2020-2022) compared to a pre-pandemic period (2000-2019). We perused data from the Remington’s Laboratory, the National Reference Laboratory for Toxoplasmosis in the US. We calculated the yearly number of cases of CT and AT-P; the incidence rate (IR) of CT and AT-P (IR=number of cases/total number of children < 12 months or pregnant women respectively tested by the Toxoplasma IgG-Dye test). We used ARIMA time-series models to compare the trajectory slopes between the two periods. Results In the pre-pandemic period there were 196 CT cases among 8194 tested children< 12 months and 814 AT-P cases among 33,345 pregnant women. The respective numbers during the pandemic were 43 CT among 1833 tested children < 12 months and 65 AT-P among 1983 pregnant women. In 2022 we had the largest number of CT cases (21 CT in 2022 vs 6 in 2019) and similarly a high number of AT-P cases (22 AT-P in 2022 vs 16 in 2019)(Fig 1). This increase occurred, despite a drop in the total number of samples tested in the Lab ≥2020, due to programmatic changes in one major Lab client (Fig 2). The yearly IR of CT increased during the pandemic, from 1.05 cases/100 tested (6/574) in 2019 to 3.71 cases/ 100 tested (21/566) in 2022. The yearly IR of AT-P also increased during the pandemic, from 1.35 cases/ 100 tested (16/1183) in 2019 to 3.79 cases/100 tested (22/580) in 2022 (Fig 3). There was a positive trajectory-slope trend in CT and AT-P during the pandemic. This occurred after a preceding negative trajectory-slope trend in AT-P in the pre-pandemic period.Figure 1:Number of Congenital Toxoplasmosis and Acute Toxoplasmosis during Pregnancy cases: 2000-2022Figure 2:Toxoplasmosis IgG Dye tests in Pregnant Women and in Children <12 months of age: 2000-2022Figure 3:Incidence Rates of Congenital Toxoplasmosis (IR-CT)and Acute Toxoplasmosis During Pregnancy (IR-AT-P): 2000-2022 Conclusion During the pandemic, there was a rising trend in CT and AT-P cases diagnosed in the National Reference Lab for toxoplasmosis in the US. In 2022 there was a peak in the CT cases. The etiology remains unclear. A possible increase- during the lockdowns-in the contact of pregnant women with cats and/or a possible limited prenatal-preventive-guidance during the pandemic due to possible disruption in prenatal care services, could have been contributing factors. These trends need further monitoring. Disclosures All Authors: No reported disclosures

Reduced neural progenitor cell count and cortical neurogenesis in guinea pigs congenitally infected with Toxoplasma gondii

Toxoplasma (T.) gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection can lead to severe pathological alterations in the brain. To examine the effects of toxoplasmosis in the fetal brain, pregnant guinea pigs are infected with T. gondii oocysts on gestation day 23 and dissected 10, 17 and 25 days afterwards. We show the neocortex to represent a target region of T. gondii and the parasite to infect neural progenitor cells (NPCs), neurons and astrocytes in the fetal brain. Importantly, we observe a significant reduction in neuron number at end-neurogenesis and find a marked reduction in NPC count, indicating that impaired neurogenesis underlies the neuronal decrease in infected fetuses. Moreover, we observe focal microglioses to be associated with T. gondii in the fetal brain. Our findings expand the understanding of the pathophysiology of congenital toxoplasmosis, especially contributing to the development of cortical malformations.

1583. Optimal timing of antiretroviral therapy initiation in AIDS-associated Toxoplasma encephalitis: a prospective observational multicenter study in China

Abstract Background Toxoplasma encephalitis (TE) is the most frequent cause of expansive brain lesions among acquired immunodeficiency syndrome (AIDS) patients; however, the optimal timing of antiretroviral therapy (ART) initiation in these patients remains controversial. Methods This was a multicenter prospective observational study, and eligible patients were recruited from eleven treatment centers in China. Results In total, 87 patients were included, and 38 of them were assigned to the Early ART group (initiating ART within 2 weeks after anti-Toxoplasma treatment initiation), while the remaining 49 patients were allocated to receive deferred ART (initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation). Our results indicated that the incidence of immune reconstitution inflammatory syndrome (IRIS) (2.6% vs. 0, p=0.437) and the number of death events (1 vs. 5, p=0.225) were not significantly different between the two groups at Week 48. The timing of ART initiation was also found to not significantly contribute to human immunodeficiency virus (HIV) viral load control. The difference in the number of patients who maintained an undetectable HIV viral load of <50 copies/mL in each of the two groups of patients was calculated to not be statistically significant at Week 24 (8 vs. 3, p=0.142) and Week 48 (7 vs. 7, p=1.000). Meanwhile, median CD4+ T-cell counts were also observed not to reach statistical significance between the two groups, both at Week 24 (155 vs. 91, p=0.837) and Week 48 (181 vs. 96, p=0.219). Conclusion In our study, early ART initiation was observed to not confer statistically significant differences in the incidence of IRIS, mortality, and HIV virological and immunological outcomes, when compared to deferred ART initiation. Disclosures All Authors: No reported disclosures

Cerebral Toxoplasmosis in a patient with Pneumocystis: a case report

Acquired Immune Deficiency Syndrome, or AIDS, is characterized by a clinical condition in which the body's defenses suffer a gradual depletion, making it susceptible to a wide variety of infections. Among these, neurotoxoplasmosis is a characteristic opportunistic infection caused by Toxoplasma gondii. This infection generates numerous neurological deficits that can regress if early diagnosis and intervention are carried out. However, underdiagnosis of these cases due to incorrect management or inaccurate diagnosis leads to damaging and permanent results due to the expansive nature of the mass, which affects a wide range of organic functions. It is then associated with infection by Pneumocystis jirovecii, also characteristic of immunodeficient patients, demonstrating a synergism between the mechanisms that facilitate the infectious process. Because of the seriousness of these infections and their association, a clinical picture like this must be well visualized.

The problem of toxoplasmosis in outpatient practice. Part III. Toxoplasmosis in pregnants and congenital toxoplasmosis

Congenital toxoplasmosis is a consequence of acute toxoplasmosis in a pregnant woman. When assessing the risk of сongenital toxoplasmosis during pregnancy, methods for determining specific antibodies, the genetic material of the pathogen (polymerase chain reaction method), immunoglobulins G avidity are used. Molecular genetic methods have the greatest diagnostic value in the diagnosis of сongenital toxoplasmosis in children of the first year of life. Drug prevention of сongenital toxoplasmosis in Russia can be implemented with the use of spiramycin, antenatal therapy is impossible, and postnatal therapy is limited by the list of available antiprotozoal drugs. For the prevention of сongenital toxoplasmosis, the awareness of the population about the ways and factors of transmission of the pathogen is of primary importance.

Comparison of B1 and RE 529 gene targets by real time PCR and LAMP assay for diagnosis of toxoplasmosis in pregnant females

PurposeThe aim of this study is to accurately diagnose the presence of toxoplasmosis in pregnant women. In this study we evaluated two gene targets B1 and RE-529 using two different molecular methods i.e., real-time PCR and LAMP. ProcedureA total of 150 blood samples were collected from pregnant women attending the PGIMER outpatient clinic. The serum and Buffy layer were extracted and various serological (ELISA) and molecular tests (qPCR and LAMP) targeting B1 and RE-529 were carried out. FindingOut of 150 patients, 32 were seropositive. Amongst which for the RE-529 gene, 18 were LAMP positive and 16 were qPCR positive, while for the B1 gene, 14 were LAMP positive and 13 were qPCR positive. ConclusionsMolecular methods were more sensitive than serological tests to diagnose congenital toxoplasmosis in antenatal females. Few seronegative patients were reported positive using molecular methods. In addition, LAMP targeting the RE-529 gene is more sensitive than qPCR, and LAMP targets the B1 gene.

Longitudinal Safety of Luspatercept in the Treatment of Anemia in Patients with Myelofibrosis: Results from the ACE-536-MF-001 Study

Introduction Luspatercept (LUSPA) is approved for the treatment of anemia in some adults with β-thalassemia or myelodysplastic syndrome who require red blood cell transfusion and has a well characterized safety profile for these indications. The primary readout from the phase 2 ACE-536-MF-001 study (NCT03194542) demonstrated manageable safety and promising efficacy of LUSPA for treatment of myelofibrosis (MF)-related anemia with 19.0%-31.6% of patients (pts) achieving transfusion independence (defined as 84 consecutive days transfusion free), and 18.2%-21.4% of non-transfusion-dependent (NTD) pts achieving anemia response (defined as 84 consecutive days ≥ 1.5 g/dL hemoglobin increase from baseline without transfusion) in the entire treatment period (Gerds ASCO 2023 7016). To characterize further the safety profile of LUSPA in MF and provide data on adverse event (AE) management, we present a detailed longitudinal safety analysis of the MF-001 study. Methods Pts were enrolled into 4 cohorts based on transfusion dependence (TD) and stable ruxolitinib (RUX) treatment - cohort 1: NTD, no RUX; cohort 2: TD, no RUX; cohort 3A: NTD, RUX; cohort 3B: TD, RUX. All pts received LUSPA 1.0 mg/kg subcutaneously with titration up to 1.75 mg/kg in 21-day cycles; the starting dose was 1.33 mg/kg in the cohort 3B expansion group. Response was assessed at day 169 (24 weeks), with treatment extended for pts showing clinical benefit. The primary endpoint was anemia response; AEs alongside LUSPA and RUX dosing were also assessed. On dosing days, seated blood pressure was assessed prior to LUSPA administration. In the case of ≥ grade 3 hypertension (systolic ≥ 160 mmHg, diastolic ≥ 100 mmHg), dosing was delayed until hypertension had resolved to ≤ grade 1 or baseline, followed by dose reduction by 1 dose level. If ≥ 2 dose reductions were implemented due to any suspected treatment-related AE (TRAE), LUSPA was discontinued. Results In the safety population (N = 95; cohort 1, n = 22; cohort 2, n = 14; cohort 3A, n = 21; cohort 3B, n = 38), the most frequently used prior medications for anemia treatment were erythropoiesis-stimulating agents (23.2%, most frequently epoetin alfa [14.7%]), followed by danazol (11.6%), lenalidomide (2.1%), and thalidomide (1.1%). Prior history of hypertension was recorded in 50.5% of pts. Median follow-up duration was 546 days. A total of 47.4% of pts had ≥ 1 TRAE; the most common were hypertension (17.9%), bone pain (7.4%), and diarrhea (6.3%). Incidence of treatment-related grade ≥ 3 diarrhea was low (2.1%). Overall, 13.7% of pts received concomitant antidiarrheals. LUSPA was discontinued in 9 pts due to AEs; 1 event of cerebral toxoplasmosis was considered treatment related by the investigator. Among pts receiving RUX (cohorts 3A/3B), hypertension was the most frequently occurring grade ≥ 3 TRAE ( Table 1) and 5 pts had LUSPA dose modifications related to hypertension events; considered related to LUSPA in 4 pts ( Table 2). In contrast, among pts not receiving RUX (cohorts 1/2), no pts experienced grade ≥ 3 hypertension events. Hypertension was manageable with clinical intervention; during the study the most frequent concomitant medications for hypertension were angiotensin-converting enzyme inhibitors (26.3%), beta-blocking agents (selective, 23.2%; non-selective, 3.2%), and angiotensin II receptor blockers (alone, 20.0%; plus diuretics, 5.3%). Among NTD pts (cohort 3A), there were no changes in RUX dose. Among TD pts (cohort 3B), 25 (65.8%) pts maintained their RUX dose and 6 (15.8%) pts had ≥ 1 dose increase. Overall, 9 deaths occurred during treatment; none were considered treatment related. Causes of death were pneumonia, septic shock, intracranial hemorrhage, ischemic stroke, organ dysfunction, post-procedural hemorrhage, myelofibrosis, renal failure, and pneumonitis (n = 1 each). Conclusions The safety profile of LUSPA in the ACE-536-MF-001 study was consistent with previous studies in other indications, and AEs were mostly low grade. In addition to benefits in anemia, the safety profile of LUSPA allowed most pts receiving RUX to maintain or increase their RUX dose, supporting maintenance of Janus kinase inhibitor therapy for adequate disease control of MF. Study support: Bristol Myers Squibb.

Resultados de la encuesta nacional de REIV-TOXO sobre el cribado gestacional de la toxoplasmosis en España

IntroductionCurrently, the status of serological screening for toxoplasmosis in pregnant women in Spain is unknown, and there is no official recommendation. The objective of this study is to show the current practice of gestational screening for toxoplasmosis in hospitals belonging to the Spanish Network for Research on Congenital Toxoplasmosis (REIV-TOXO). MethodsAn electronic survey was sent between April 2021 and September 2021 to investigators from 118 hospitals of REIV-TOXO, representing all Spanish regions. Nine items related to gestational screening for toxoplasmosis were collected. This information was compared with cases of congenital toxoplasmosis (CT) identified in REIV-TOXO to determine if these were diagnosed in the presence of gestational screening. ResultsDuring the study period, serological screening was performed in 53.3% (63/118) hospitals, with variations between regions and even among hospitals within the same region. Testing performed in each trimester was the most common practice (57.7%), followed by a single determination (24.4%). 89.4% of CT cases between January 2015 and September 2021 were diagnosed due to gestational screening. ConclusionThe decision to perform gestational screening for toxoplasmosis in Spain is highly heterogeneous, with significant local and regional differences. Despite this, screening still allows the diagnosis of most CT cases. It is urgent to have current epidemiological data to inform decision-making in public health.

Past and present seroprevalence and disease burden estimates of Toxoplasma gondii infections in Germany: An appreciation of the role of serodiagnostics

Toxoplasmosis is one of the major foodborne parasitic diseases in Germany, with 49% of its population chronically infected with its causative agent, Toxoplasma gondii. Although the acute disease is usually benign in immunocompetent individuals, it is a threat for immunocompromised patients as well as for fetuses of seronegative mothers. As a result of infection, congenital and ocular toxoplasmosis can have serious lifelong consequences. Here I will highlight the epidemiologic situation, from its past in the two separate parts of Germany, to its unification 30 years ago and up to the present day. The main identified risk factor for infection in Germany is thought to be the consumption of undercooked or raw meat or sausages. However, the relative impact of this risky eating habit as well as that of other risk factors are changing and are discussed and compared to the situation in the Netherlands. Finally, the importance of robust and efficient high-throughput serological assays for obtaining reliable epidemiological data, on which public health decisions can be made, is highlighted. The potential of bead-based multiplex assays, which allow the incorporation of multiple antigens with different analytical properties and thus yield additional information, are described in this context. It illustrates the interdependence of new analytic assay developments and sound epidemiology, a foundation that decades-old data from Germany did not have.

Clinical and Metagenomic Characterization of Neurological Infections of People With Human Immunodeficiency Virus in the Peruvian Amazon.

Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose. One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses. Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score (P = .05), unilateral focal motor signs (P = .01), positive Babinski reflex (P = .01), and multiple lesions on head computed tomography (CT) (P = .002) were associated with cerebral toxoplasmosis. Photophobia (P = .03) and absence of lesions on head CT (P = .02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for T gondii. mNGS had a sensitivity of 78% and specificity of 100% for Cryptococcus diagnosis. An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections.

An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii.

Congenital toxoplasmosis in humans and in other mammalian species, such as small ruminants, is a well-known cause of abortion and fetal malformations. The calcium-dependent protein kinase 1 (CDPK1) inhibitor BKI-1748 has shown a promising safety profile for its use in humans and a good efficacy against Toxoplasma gondii infection in vitro and in mouse models. Ten doses of BKI-1748 given every other day orally in sheep at 15 mg/kg did not show systemic or pregnancy-related toxicity. In sheep experimentally infected at 90 days of pregnancy with 1000 TgShSp1 oocysts, the BKI-1748 treatment administered from 48 hours after infection led to complete protection against abortion and congenital infection. In addition, compared to infected/untreated sheep, treated sheep showed a drastically lower rectal temperature increase and none showed IgG seroconversion throughout the study. In conclusion, BKI-1748 treatment in pregnant sheep starting at 48 hours after infection was fully effective against congenital toxoplasmosis.