Toxoplasmosis Research Articles

Detection of Congenital Toxoplasmosis and Cytomegalovirus Infections Using Paired Sample Serodiagnosis from Suspected Cases at a Tertiary Teaching Hospital in Malaysia.

Congenital toxoplasmosis and congenital cytomegalovirus (cCMV) infections are noteworthy in Malaysia and can cause serious health problems in neonates. The prompt and effective detection and treatment related to both illnesses may mitigate the possibility of adverse consequences from both infections. A total of 219 neonates with suspected clinical indications of congenital toxoplasmosis and/or cCMV infections from January 2022 to December 2022 were enrolled. The first samples for IgM and IgG antibodies were screened by electrochemiluminescence immunoassay. For positive results indicative of congenital toxoplasmosis and cCMV infections, second serum samples were requested and tested within a period of 2-4 weeks after testing the first sample. From the 219 first serum samples, the overall seroprevalence of congenital toxoplasmosis antibodies in suspected cases was 53%; meanwhile, the overall seroprevalence of cCMV in the suspected cases was 98.6%. The results of the paired serum sample collected for investigating congenital toxoplasmosis cases revealed that 47% of the cases presented no serological evidence of exposure while the remaining 53% of cases might have acquired passive immunity from the mother. For cCMV, the number of cases with no serological evidence of exposure was 1.4%, whereas acute infection was 1.8% and possible passive immunity from the mother represented 96.8%. This study found a high seroprevalence of congenital toxoplasmosis and cCMV infections, probably because they are suspected cases. This study also indicates that using paired sample analysis in the categorisation of cases can aid in accurate diagnosis and more effective treatment.

People living with HIV presenting with hemiparesis: what are the possible causes?

People living with HIV (PLWH) are commonly associated with opportunistic infections, particularly with low CD4 count, less than 200 cells/μL. Neurological manifestation can be occurred 70% in PLWH and the most symptoms is hemiparesis, seizure, headache, behavioural changes, decrease of consciousness, and cognitive impairment but depends on the localization of the brain lesions. We present a case of 53-year-old man with initial presentation of right hemiparesis and was on highly active antiretroviral therapy (HAART). With laboratory and CT-scan result, the patient diagnosed with stroke ischemic and occurred at the same time with toxoplasma encephalitis (TE) as an opportunistic infection. In PLWH, many possible causes involve central nervous system-caused hemiparesis. The initial differential diagnosis should be considered to prevent delayed treatment and potential of severe complications.

Neurosurgical Interventions in Patients With Cerebral Toxoplasmosis

Toxoplasmosis of the brain is a pressing issue in the practice of neurologists and neurosurgeons. Most patients with cerebral toxoplasmosis are persons with AIDS. However, toxoplasmic encephalitis can develop in patients with any immunodeficiency conditions that lead to reactivation of toxoplasmosis infection in the central nervous system. Although cerebral toxoplasmosis is not a neurosurgical pathology, patients sometimes require neurosurgical interventions: diagnostic biopsy and lesion removal. Moreover, literature shows cases of removal of brain lesions initially mistaken for a brain tumor, which, as a rule, occurs when the patient’s HIV status is unknown and the severity of their condition does not allow for a comprehensive additional examination.This article reviews Russian and foreign publications on neurosurgical interventions in patients with cerebral toxoplasmosis.

CHALLENGE IN TREATING OPTIC NEURITIS IN PATIENT WITH CEREBRAL TOXOPLASMOSIS RELATED TO IMMUNOCOMPROMISED CONDITION

Introduction: This study aimed to discuss the prognosis of optic neuritis in a patient with cerebral toxoplasmosis related to an immunocompromised condition. Case Report: A 28-year-old female complained of blurred vision and double vision 2 weeks before admission, accompanied by headache, low extremities weakness, dysphonia, and dysphagia. Visual acuity of both eyes was 6/30 and worsened to 6/60 in a couple of days. Anterior segment examination revealed anisocoria pupil, and RAPD was positive in the left eye. Funduscopic examination showed a blurry margin and hyperemia of the optic nerve head. There was impaired eye movement, indicating oculomotor and abducens nerve palsies. High titer of IgG Antibody Toxoplasma (264) and very low titer of CD4 (<50) with non-reactive HIV rapid test were found in laboratory findings. Multiple ring enhancement was shown in MRI finding. Unfortunately, patient passed away during hospitalization due to respiratory failure. Discussion: Toxoplasmosis-associated optic neuritis is rare and usually becomes potentially serious. Although parasite detection by microscopy and bioassay is considered the gold standard for the diagnosis of toxoplasmosis, clinical diagnosis relies more on serological examination methods. The high proportion of deaths from this disease is mostly caused by late diagnosis of the infection. Conclusion: Optic neuritis that accompanied by systemic disorders needs special attention and comprehensive treatment among multidisciplinary divisions, especially in the immunocompromised condition. Early detection and primary prevention are important to improve prognosis and survival rate.

Longitudinal Study of Cognitive Function in People with HIV and Toxoplasmic Encephalitis or Latent toxoplasma Infection.

Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related CNS co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on NC functioning in PWH with TE compared to LTI or no toxoplasmal infection. PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti-Toxoplamic IgG assay. Participants were classified into one of three groups: TE+ (n = 39), LTI+ (n = 34), LTI- (n = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit. The mean age was 48 ± 11 years, mean educational level 13 ± 3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/mL) and had lower absolute CD4 counts. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI- participants. PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.

Церебральный токсоплазмоз у ВИЧ-инфицированных пациентов в клинической практике

Cerebral toxoplasmosis is one of the most common opportunistic infections in HIV-infected patients. Neurological disorders in this group of patients require a differential diagnosis with demyelinating diseases, toxic damage to the nervous system, acute cerebrovascular accident and brain tumors. Cerebral toxoplasmosis can be accompanied by damage to internal organs and be combined with other secondary diseases in HIV-infected patients who are not aware of the presence of HIV-infection or hide this fact. Therefore, it becomes important to inform doctors of all specialties about features of clinical manifestations and the course of this pathology, which will allow early diagnosis and timely prescribing of effective therapy for the disease.

The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long-time experience of a tertiary referral centre.

Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole. Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.

Congenital Toxoplasmosis and Late Retinochoroiditis

Congenital Toxoplasmosis and Late Retinochoroiditis

Could metformin modulate the outcome of chronic murine toxoplasmosis?

Toxoplasmosis is a pervasive parasitic infection possessing a chief impact on both public health and veterinary medicine. Unfortunately, the commercially-available anti-Toxoplasma agents have either serious side effects or diminished efficiency, specifically on the Toxoplasma tissue cysts. In the present study, metformin (The first-line treatment for type 2 diabetes mellitus) was investigated for the first time against chronic cerebral toxoplasmosis in mice model experimentally-infected with ME49 strain versus spiramycin. Two metformin regimens were applied; starting one week before the infection and four weeks PI. Parasitological, ultrastructural, histopathological, immunohistochemical, immunological, and biochemical assessments were performed. The anti-parasitic effect of metformin was granted by the statistically-significant reduction in tissue-cyst burden in both treatment regimens. This was accompanied by markedly-mutilated ultrastructure and profound amelioration of the cerebral histopathology with remarkable decline in the brain CD4+ and CD8+ T cell count. Besides, diminution of anti-Toxoplasma IgG and brain GSH levels was evident. Ultimately, the present findings highlighted the powerful promising therapeutic role of metformin in the management of chronic toxoplasmosis on a basis of anti-parasitic, anti-inflammatory, and anti-oxidant possessions.

CCR2-dependent placental migration of inflammatory monocytes suppresses abnormal pregnancies caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gongii) is a zoonotic protozoan parasite that causes congenital toxoplasmosis, including fetal death, abortion, stillbirth, morphological abnormalities, and premature birth. Primary T. gondii infection in pregnant women results in congenital toxoplasmosis. C-C chemokine receptor (CCR) 2 is reportedly a critical host defense factor against T. gondii infection. However, details of the role of CCR2 in the host immune response to T. gondii in congenital toxoplasmosis remain unclear. Here, we infected pregnant CCR2-deficient mice with T. gondii, resulting in stillbirth, embryonic resorption, fetal morphological abnormalities, and preterm delivery at significantly higher rates than those in pregnant wild-type mice. Consistent with the severity of abnormal pregnancy, a large area of placental hemorrhage and a large number of T. gondii infections around the hemorrhagic area were observed in the placentas of CCR2-deficient mice. In addition, the accumulation of inflammatory monocytes in the placenta was reduced in CCR2-deficient mice during infection. We further confirmed that the adoptive transfer of inflammatory monocytes collected from wild-type mice into T. gondii-infected pregnant CCR2-deficient mice effectively suppressed placental damage and abnormal pregnancy. Collectively, CCR2 contributes to pregnancy maintenance by regulating the migration of inflammatory monocytes into the placenta of T. gondii-infected pregnant mice.

Investigation of Toxoplasma gondii Seroprevalence in Pregnant Women in Çankırı

Toxoplasma gondii can be transmitted to humans through consumption of raw or undercooked meat containing live tissue cysts, consumption of water or food contaminated with oocysts shed from cat feces, and vertical transmission during pregnancy or through tissue, organ, and blood transfusion. The aim of this study was to investigate the seroprevalence of T. gondii in patients admitted to the Obstetrics and Gynecology Department of Çankırı State Hospital (ÇSH). In this study, anti-T. gondii IgG and IgM antibody levels of 62 pregnant women between the ages of 17 and 47 who applied to ÇSH gynecology and obstetrics outpatient clinic for normal pregnancy follow-up between June 2022 and January 2023 were investigated. According to the results of the studies, anti-T gondii IgG positivity is 12.9% and negative 87.1% and anti-T. gondii IgM positivity is 0% while it was found to be 100% negative. According to these results, it is reported that the majority of pregnant women do not encounter T. gondii and; therefore, they should be more careful in terms of congenital toxoplasmosis. T. gondii can be transmitted to humans through consumption of water or food contaminated with oocysts excreted in cat feces and through vertical transmission or tissue, organ, and blood transfusion during pregnancy. Therefore, pregnant women should be carefully monitored for T. gondii.

Medical termination of pregnancy with digoxin in a patient affected by severe congenital toxoplasmosis.

SynopsisIntrafetal digoxin is a safer and effective alternative to perform medical termination of pregnancy over intracardiac potassium chloride in cases of massive placental inflammation, such as congenital infections.

Neuroimaging in the diagnosis and treatment of cerebral toxoplasmosis in children with severe β-thalassemia after allo-HSCT.

Children with severe β-thalassemia major (β-TM) are at high risk of developing toxoplasmosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to identify the neuroimaging findings of cerebral toxoplasmosis in pediatric patients with β-TM for early diagnosis and treatment of cerebral toxoplasmosis. We performed a retrospective assessment of clinical and neuroimaging data of children with severe β-TM who had cerebral toxoplasmosis after allo-HSCT. Additionally, we reviewed and summarized the literature on cerebral toxoplasmosis in patients with other underlying conditions. This case series identified three children who had severe β-TM and had subsequent cerebral toxoplasmosis after allo-HSCT. In addition, we identified 23 patients from literature who had toxoplasmosis and had underlying conditions other than β-TM. We found that the most common clinical symptom among the patients from our series and the patients from literature was fever upon presentation. We identified the typical neuroimaging findings including brain lesions with ring enhancement and eccentric/central nuclear target-like enhancement, which should facilitate early diagnosis and treatment of cerebral toxoplasmosis.

Interleukins IL33/ST2 and IL1-β in Intrauterine Growth Restriction and Seropositivity of Anti-Toxoplasma gondii Antibodies.

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis. It may produce severe damage in immunocompromised individuals, as well as congenital infection and intrauterine growth restriction (IUGR). Previous reports have associated interleukin IL-33 with miscarriage, fetal damage, and premature delivery due to infections with various microorganisms. However, IL-33 has not been associated with congenital toxoplasmosis. The sST2 receptor has been reported in patients who have had recurrent miscarriages. On the other hand, IL-1β was not found in acute Toxoplasma infection. Our aim was to analyze the associations between the serum levels of IL-33 and IL-1β in IUGR and toxoplasmosis during pregnancy. Eighty-four serum samples from pregnant women who had undergone 26 weeks of gestation were grouped as follows: with anti-Toxoplasma antibodies, without anti-Toxoplasma antibodies, IUGR, and the control group. IgG and IgM anti-T. gondii antibodies, as well as IL-33, ST2, and IL-1β, were determined using an ELISA assay. Statistical analyses were performed using the Pearson and Chi-square correlation coefficients, as well as the risk factors and Odds Ratios (ORs), with a confidence interval of 95% (CI 95). The results showed that 15/84 (17.8%) of cases were positive for IgG anti-Toxoplasma antibodies and 2/84 (2.38%) of cases were positive for IgM. A statistically significant difference was found between IUGR and IL-33 (p < 0.001), as well as between ST2 and IUGR (p < 0.001). In conclusion, IUGR was significantly associated with IL-33 and ST2 positivity based on the overall IUGR grade. No significant association was found between IUGR and the presence of anti-Toxoplasma antibodies. There was no association between IL-1β and IUGR. More research is needed to strengthen the utility of IL-33 and ST2 as biomarkers of IUGR.

Clinical manifestations and imaging analysis of hepatitis C complicated with cerebral toxoplasmosis

Clinical manifestations and imaging analysis of hepatitis C complicated with cerebral toxoplasmosis

Difficulty in diagnosing intracranial infection caused by Mycobacterium avium in an AIDS patient: case report and review of the literature

BackgroundMycobacterium avium complex (MAC) is an uncommon clinical pathogen, especially in the central nervous system (CNS), and carries a poor prognosis. MAC infections commonly present as immune reconstitution disease (IRD) in HIV patients. Herein, we report a case of intracranial infection caused by MAC in an AIDS patient without disseminated MAC (DMAC) and immune reconstitution inflammatory syndrome (IRIS).Case presentationA 31-year-old HIV-positive male presented us with progressively worsening CNS symptoms, and neuroimaging revealed ring-enhancing lesions. The intracranial lesions worsened after the empirical therapy for toxoplasma encephalitis and fungal infection. Due to the rapid progression of the disease, the patient died. Mycobacterium avium was the only pathogen in brain tissue after cultures and molecular biology tests.ConclusionMAC infection in CNS is challenging to diagnose in HIV patients. Our findings emphasize that obtaining tissue samples and applying molecular biology methods is essential to help diagnose the patient as soon as possible to receive adequate treatment.

Development of a LAMP method with lateral flow DNA chromatography to diagnose toxoplasmosis in immunocompromised patients

BackgroundRapid and accurate diagnosis of toxoplasmosis is critical, particularly for immunocompromised patients. Several molecular methods could have value for toxoplasmosis diagnosis, but often require sophisticated and expensive equipment, and as such are impractical for use in resource-limited countries. Our study aimed to develop a new rapid diagnostic test for toxoplasmosis that can be used in developed countries as well as low- or middle-income countries.MethodsCommon primers for conventional loop-mediated isothermal amplification (LAMP) and the new LAMP DNA chromatography method were designed based on a 529-bp repeat present in Toxoplasma gondii genomic DNA. A total of 91 clinical samples from 44 patients suspected of having toxoplasmosis who were treated at several hospitals across Japan were tested using the new LAMP DNA chromatography method, conventional LAMP, and nested PCR and the sensitivity and specificity of the methods was compared.ResultsThe LAMP DNA chromatography method showed better sensitivity and specificity (68.2% and 100%, respectively) compared with the nested PCR (45.4% and 100%, respectively) and conventional LAMP (63.6% and 100%, respectively) methods for diagnosis of toxoplasmosis in immunocompromised patients. LAMP DNA chromatography also has better sensitivity and specificity (75% and 100%, respectively) than nested PCR (50.0% and 93.5%, respectively) and conventional LAMP (62.5% and 100%, respectively) to diagnose toxoplasma encephalitis using CSF samples.ConclusionWe developed a LAMP DNA chromatography method to detect T. gondii DNA in clinical samples. This method also successfully detected T. gondii DNA in CSF from patients with toxoplasma encephalitis. This newly developed method can be a valuable rapid diagnostic test for toxoplasmosis in a range of settings, including resource-limited areas like those in low- or middle-income countries.

Therapeutic potential of Garcinia kola against experimental toxoplasmosis in rats.

Cerebral toxoplasmosis, the most common opportunistic infection in immunocompromised individuals, is increasingly reported in immunocompetent individuals due to mutant strains of Toxoplasma gondii, which, furthermore, are reported to be resistant to available treatments. We assessed the therapeutic potential of Garcinia kola, a medicinal plant reported to have antiplasmodial and neuroprotective properties, against experimental toxoplasmosis in rats. Severe toxoplasmosis was induced in male Wistar rats (156.7 ± 4.1 g) by injecting them with 10 million tachyzoites in suspension in 500 µl of saline (intraperitoneal), and exclusive feeding with a low-protein diet [7% protein (weight by weight)]. Then, animals were treated with hexane, dichloromethane, and ethyl acetate fractions of Garcinia kola. Footprints were analysed and open-field and elevated plus maze ethological tests were performed when symptoms of severe disease were observed in the infected controls. After sacrifice, blood samples were processed for Giemsa staining, organs were processed for haematoxylin and eosin staining, and brains were processed for Nissl staining and cell counting. Compared with non-infected animals, the infected control animals had significantly lower body weights (30.27%↓, P = 0.001), higher body temperatures (P = 0.033) during the sacrifice, together with signs of cognitive impairment and neurologic deficits such as lower open-field arena centre entries (P < 0.001), elevated plus maze open-arm time (P = 0.029) and decreased stride lengths and step widths (P < 0.001), as well as neuronal loss in various brain areas. The ethyl acetate fraction of Garcinia kola prevented or mitigated most of these signs. Our data suggest that the ethyl acetate fraction of Garcinia kola has therapeutic potential against cerebral toxoplasmosis.

Profile of HIV/AIDS Patients with Neurological Manifestations in The Tertiary Referral Hospital in Bali

Background: Neurological manifestations in approximately half of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) patients are related to high morbidity and mortality worldwide. Therefore, there is a need for epidemiological data on HIV/AIDS patients with neurological manifestations in Bali, as an international tourism destination. Objective: This study aimed to describe the clinical profile of neurological manifestations among patients with HIV/AIDS in the tertiary referral hospital for Bali and Nusa Tenggara region. Methods: A descriptive-retrospective study was conducted on HIV/AIDS patients presenting with neurological manifestations hospitalized in the Neurology Department of Prof. Dr. I.G.N.G Ngoerah Hospital Denpasar from January 2018 to December 2021. Results: Among the 227 subjects included in this study, the majority were male (69.9%) and HIV positive newly diagnosed (69.2%). Furthermore, out of 126 subjects who had CD4 data, the majority were with CD4 &lt;200 cells/mm3 (85.7%) and 53.1% were &lt;50 cells/mm3, with ages ranging from 18 to 67 years old, at a median of 36 years old. The most common neurological signs and symptoms found were paresis/paralysis (61.7%), headache (54.6%), decreased consciousness (52.9%), and cranial nerve palsy (52%). Cerebral toxoplasmosis (67.4%) and tuberculous meningoencephalitis (20.3%) were the prevalent opportunistic infections, while the mortality rate was 39.6% with sepsis as the major cause. Conclusions: Neurological manifestations are common initial symptoms in diagnosing HIV infection. Therefore, better awareness and earlier detection are required among people with risk factors of HIV transmission, particularly in groups of young and productive age with signs of immunocompromised condition as well as neurological manifestations.

COGNITIVE FUNCTION ASPECTS IN HIV-ASSOCIATED CEREBRAL TOXOPLASMOSIS: A CASE REPORT

HIV-associated cerebral toxoplasmosis may lead to cognitive function impairment through accumulation of β-amyloid plaques and Tau protein which cause damage, inflammatory and oxidative processes in the brain. A 40-year-old, Balinese, right-handed female patient, came with chief complaint of three times of seizure before admission. After the seizures stopped, the patient was fully conscious again. Since the last 2 months, the patient seemed more confused and spoke a little slower. The patient also often repeated a story about something and forgot that she had already told it. The patient has a known history of HIV infection in the past 3 months before admission, she had taken anti-retroviral agents but she stopped them by herself since last 1 month. Anti-Toxoplasma IgG antibody showed reactive results and CD-4 of 62 cells/µL. The results of the overall cognitive function examination found mild cognitive impairment with activities that required mild assistance. HIV-associated neurocognitive disorders (HAND) are still a challenge to study, and the importance of improving patient cognitive function to maintain or increase aspects of independence and quality of life is a target in the care of HIV patients, especially patients with HIV-associated cerebral toxoplasmosis infection.