Toxoplasmosis

doi:10.1016/j.siny.2007.01.011

Seminars in Fetal and Neonatal Medicine

Volume 12, Issue 3, June 2007, Pages 214-223

https://doi.org/10.1016/j.siny.2007.01.011 Get rights and content

Summary

Infections with Toxoplasma gondii occur worldwide, but are especially prevalent in Europe, South America and Africa. The primary problem for the diagnosis of T. gondii infection is long-lasting IgM-antibodies, thus the presence of T. gondii-specific IgM-antibodies do not necessarily indicate an acute infection. The use of a Toxoplasma-specific IgG-avidity ratio, differentiated Western blots and two-dimensional immunoblots usually resolves diagnostic problems. There is no consensus on the best strategy to control congenital toxoplasmosis. Recent European prospective, but descriptive, studies including a meta-analysis of existing cohorts have found a surprisingly small effect on maternal–fetal transmission and clinical signs in children treated for T. gondii infection diagnosed by pre- and neonatal screening programmes. No randomised studies exist on the treatment of T. gondii infection in pregnant women and newborn children with congenital toxoplasmosis. Atovaquone is the most promising new drug available, but is not yet approved for use in pregnant women and small children.

Section snippets

Prevalence of infection with Toxoplasma gondii

Toxoplasma gondii occurs worldwide, but its incidence is higher in tropical areas and decreases with increasing latitude. Seroprevalence in Europe is high, up to 54% in Southern European countries and it decreases with increasing latitude to 5–10% in northern Sweden and Norway.1, 2 The age-specific prevalence has been decreasing in Europe over the past three to four decades.3, 4 The study National Health and Nutrition Examination Study (NHANES: 1999–2000) and the NHANES III (1988–1994) from the

T. gondii infection in pregnancy

If a pregnant woman acquires primary infection in pregnancy, T. gondii may be transmitted to the fetus and cause inflammatory lesions that may lead to permanent neurological damage, with or without hydrocephalus, and chorioretinitis with visual impairment. The pregnant woman and the infected newborn are often asymptomatic but the child is at risk of recurring chorioretinitis later in life.

How to best prevent damage due to congenital toxoplasmosis is a matter of debate and recent collaborative

Risk factors for infection with T. gondii

There is no biological test that can distinguish infections due to oocysts transmitted from felines, from tissue cysts ingested from infected meat.14, 15 Therefore, epidemiological surveys examining risk factors in infected and non-infected persons remain the most useful way of assessing the relative importance of different sources of T. gondii infection in humans.

A prospective case–control study from Norway in 1992–1994 found that eating raw or undercooked meat and meat products, poor kitchen

T. gondii genotypes, distribution and pathogenicity

Toxoplasma gondii can be divided into three main genotypes.21, 22 Genotype II is the most prevalent type in Europe.²³ It has been proposed that the different genotypes may be partly responsible for the different pathogenicities observed in the infection. Recent work, however, suggests a more complicated picture in Brazil, with both pathogenic and apathogenic isolates overall belonging to genotype I.24, 25 One study has reported an unusual abundance of type I and recombinant strains in patients

Diagnosis of T. gondii infections in pregnant women

The majority of maternal infections are subclinical and serological methods form the basis for diagnosis. In countries where pre-natal screening programmes are in place a test of the first blood sample from the pregnant women for Toxoplasma-specific IgM- and IgG-antibodies is performed. Conversion from seronegative to IgM/IgG-positive forms a solid basis for diagnosis. The interpretation of a finding of specific IgM and IgG may be more difficult as approximately 5% of seropositive women in the

Diagnosis of fetal infection

Molecular diagnostic techniques—such as polymerase chain reaction (PCR)—should be considered the gold standard for diagnosis of in utero infection. Sensitivity in initial reports was 100%, but subsequent studies have indicated this is very dependent on gestational age of infection.41, 42 Sensitivity also varies with the gene target (e.g. the B1 gene is present at 35 copies and AF146527 is present at 300 copies). In a French study of 2000 consecutive amniotic fluid samples it has been confirmed

Diagnosis of T. gondii infection in live-born neonates

IgM- and IgA antibodies do not cross the placenta and form the basis for serodiagnosis of congenital infection. Neonatal screening programmes for congenital toxoplasmosis are based on the detection of Toxoplasma-specific IgM-antibodies eluted from blood spots on phenylketonuria (PKU)-filter papers (Guthrie-cards).44, 45 It has been hypothesised that treatment of acute toxoplasmosis during pregnancy reduced the duration of the Toxoplasma-specific IgM response, but two studies did not find such

Systematic screening for T. gondii infection during pregnancy

Congenital infection of the fetus in women infected just before conception is extremely rare and even during the first few weeks of pregnancy the maternal–fetal transmission rate is only a few percent.⁴³

Strategies for control and prevention of congenital toxoplasmosis vary between countries and the different strategies for controlling congenital toxoplasmosis in Europe have recently been reviewed.⁵⁶ Prenatal screening is performed in Austria, France and Slovenia and neonatal screening in the

Prevention of clinical signs and symptoms in newborns with congenital T. gondii infections identified by neonatal screening

Neonatal screening for congenital toxoplasmosis is performed in New England, USA, Denmark and parts of Brazil by analysing the blood samples obtained on Guthrie cards on day 5 post-partum.72, 73 Approximately 15–55% of congenitally infected children do not have detectable Toxoplasma-specific IgM-antibodies at birth or early infancy.74, 75 Neonatal screening is performed under the assumption that early identification of congenital T. gondii infection followed by chemoprophylaxis will reduce the

No screening policy

Twenty-one European countries do not recommend screening for congenital toxoplasmosis.⁶⁵ The rationale given by these countries for not recommending screening is diverse: unfavourable cost–benefit return, absence of satisfactory treatment, programme not possible or too expensive, or incidence of toxoplasmosis infection too low.49, 50, 65, 80, 81, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96

Postnatal treatment

Postnatal treatment is given from 3 months (Denmark),49, 84, 91 to 2 years in some centres in France⁹⁷ and Switzerland.⁹⁸ The use of pyrimethamine and sulphonamides for treatment is based on animal studies performed during the 1950s and has recently been reviewed.⁹⁹

One study reported 102 cases of congenital toxoplasmosis: 68 were diagnosed prospectively from a systematic screening of pregnant women, 34 were diagnosed retrospectively because of clinical signs or because of abnormal serology during

Treatment of symptomatic, congenital T. gondii infection

A follow up study of a cohort of 120 children with severe, congenital T. gondii infection found an improved outcome in children receiving 1 year of treatment with sulphadiazine and pyrimethamine compared to historical controls.¹⁰³ The problem with these studies is the lack of knowledge of the natural history of the course of the infection, recruitment of severe cases resulting in a selection bias and a lack of control groups.

Children born with symptomatic T. gondii infection should be treated (

New drugs

The most promising new drug for the treatment of T. gondii is atovaquone and studies in mice suggest that it may be partially effective against the tissue cyst.104, 105, 106, 107 Azithromycin has also been found to have a partial effect on T. gondii tissue cysts.¹⁰⁶ Of major interest is the activity of atovaquone on cysts; in vitro treatment of cysts isolated from the brain of chronically infected mice resulted in loss of viability and infectivity of intracystic parasites (bradyzoites). Other

Side effects from treatment and chemoprophylaxis

Few studies have monitored the adverse reaction to treatment and chemoprophylaxis in a systematic way. The Chicago study of referred cases with severe, congenital toxoplasmosis reported that 58% (21/36) had transient, reversible neutropenia which in some cases required a cessation of treatment or an increase in the dose of folinic acid.⁸⁹ A study of children with congenital toxoplasmosis found that 14.6% experienced a change of dose or discontinuation of treatment due to suspected adverse

Drug resistance in T. gondii

There is no clear clinical evidence of selection of resistance under drug pressure in human¹¹¹ and few clinical or genetic data are available about drug resistance to folate inhibitors. Resistance of T. gondii to sulphonamide can be induced experimentally¹¹² and it has been related to a mutation located on codon DHPS-407. This mutation has also been evidenced on a clinical isolate (among 32 human strains) obtained from a congenitally infected child and the authors suggested that this mutation

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Toxoplasma gondii is a neurotropic single–celled zoonotic parasite that can infect human beings and animals. Infection with T. gondii is usually asymptomatic in immune–competent individual, however, it can cause symptomatic and life–threatening conditions in immunocompromised individuals and in developing foetuses. Although the mechanisms that allow T. gondii to persist in host cells are poorly understood, studies in animal models have greatly improved our understanding of Toxoplasma–host cell interaction and how this interaction modulates parasite proliferation and development, host immune response and virulence of the parasite. T. gondii is capable of recruiting the host endoplasmic reticulum (ER), suggesting it may influence the host ER function. Herein, we provide an overview of T. gondii infection and the role of host ER during stressed conditions. Furthermore, we highlight studies that explore T. gondii's interaction with the host ER. We delve into how this interaction activates the unfolded protein response (UPR) and ER stress-mediated apoptosis. Additionally, we examine how T. gondii exploits these pathways to its advantage.
Maternal anti-Toxoplasma gondii antibodies IgG2, IgG3 and IgG1 are markers of vertical transmission and clinical evolution of toxoplasmosis in the offspring
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Toxoplasma gondii can be transmitted vertically during pregnancy and may cause neurological, ocular, and even systemic damage to the offspring. Congenital toxoplasmosis (CT) can be diagnosed during gestation and/or after birth in the postnatal period. The timely diagnosis is highly relevant for efficient clinical management. The most common laboratory methods for diagnosing CT are based on Toxoplasma-specific humoral immune responses. However, these methods are of low sensitivity or specificity. In a previous study with a small number of cases, the comparison of anti-T. gondii IgG subclasses between mothers and their offspring showed promising results for CT diagnosis and prognosis. Thus, in this work, we analyzed specific IgG subclasses and IgA in 40 T. gondii-infected mothers and their children, of which 27 were congenitally infected and 13 uninfected. A higher frequency of anti-Toxoplasma IgG2, IgG3, IgG4, and IgA antibodies was observed in mothers and congenitally infected offspring. Of these, IgG2 or IgG3 were statistically the most conspicuous. In the CT group, maternal IgG3 antibodies were significantly associated with severe disease of the infants and IgG1 and IgG3 with disseminated disease. The results support that maternal anti-T. gondii IgG3, IgG2 and IgG1 are markers of congenital transmission and severity/spread of disease in the offspring.
Biogenic silver nanoparticles (AgNp-Bio) restore testosterone levels and increase TNF-α and IL-6 in Leydig cells infected with Toxoplasma gondii
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Toxoplasma gondii, a protozoan parasite, is responsible for toxoplasmosis. The available therapy for patients with toxoplasmosis involves a combination of pyrimethamine and sulfadiazine, which have several adverse effects, including bone marrow suppression, megaloblastic anemia, leukopenia, and granulocytopenia. The development of therapeutic alternatives is essential for the management of toxoplasmosis, emphasizing the recent advances in nanomedicine. This study aimed to evaluate the in vitro effects of biogenic silver nanoparticles (AgNp-Bio) on tachyzoite forms and Leydig cells infected with T. gondii. We observed that the AgNp-Bio reduced the viability of the tachyzoites and did not exhibit cytotoxicity against Leydig cells at low concentrations. Additionally, treatment with AgNp-Bio reduced the rate of infection and proliferation of the parasite, and lowered the testosterone levels in the infected cells. It increased the levels of IL-6 and TNF-α and reduced the levels of IL- 10. Among the morphological and ultrastructural changes, AgNp-Bio induced a reduction in the number of intracellular tachyzoites and caused changes in the tachyzoites with accumulation of autophagic vacuoles and a decrease in the number of tachyzoites inside the parasitophorous vacuoles. Collectively, our data demonstrate that the AgNp-Bio affect T. gondii tachyzoites by activating microbicidal and inflammatory mechanisms and could be a potential alternative treatment for toxoplasmosis.
Biogenic silver nanoparticles reduce Toxoplasma gondii infection and proliferation in RAW 264.7 macrophages by inducing tumor necrosis factor-alpha and reactive oxygen species production in the cells
2022, Microbes and Infection
Owing to the serious adverse effects caused by pyrimethamine and sulfadiazine, the drugs commonly used to treat toxoplasmosis, there is a need for treatment alternatives for this disease. Nanotechnology has enabled significant advances toward this goal. This study was conducted to evaluate the activity of biogenic silver nanoparticles (AgNp-Bio) in RAW 264.7 murine macrophages infected with the RH strain of Toxoplasma gondii. The macrophages were infected with T. gondii tachyzoites and then treated with various concentrations of AgNp-Bio. The cells were evaluated by microscopy, and culture supernatants were collected for ELISA determination of their cytokine concentration. Treatment with 6 μM AgNp-Bio reduced the infection and parasite load in infected RAW 264.7 macrophages without being toxic to the cells. The treatment also induced the synthesis of reactive oxygen species and tumor necrosis factor-alpha (both pro-inflammatory mediators), which resulted in ultrastructural changes in the tachyzoites and their intramacrophagic destruction. Our findings suggest that AgNp-Bio affect T. gondii tachyzoites by activating microbicidal and pro-inflammatory mechanisms and may be a potential alternative treatment for toxoplasmosis.
Molecular detection of Toxoplasma gondii in placentas of women who received therapy during gestation in a toxoplasmosis outbreak
2022, Infection, Genetics and Evolution
Toxoplasmosis is a disease caused by T. gondii, a protozoa which affects humans and animals and is widely distributed worldwide. In humans, there is great concern due to the serious consequences that can occur in the infection of pregnant women and the newborn. The early diagnosis of gestational toxoplasmosis is important for treatment to be carried out in order to prevent vertical transmission or reduce damage. The diagnosis can be made through the detection of antibodies in pregnant women or neonates and PCR of amniotic fluid. Previous studies have also reported PCR of the placenta as a good diagnostic test. Our study evaluated the detection of T. gondii DNA in placenta samples from parturients seen at the University Hospital of Santa Maria, Southern Brazil and treated during the pregnancy. We performed PCR in forty samples and five were positive, representing 12.5%. When correlating the treatment time and the detection of DNA in the placentas, no significant result was found. The prevalence of positive samples was lower than in other studies in the literature. The data reaffirm the importance of carrying out the analysis of the placenta.
Biogenic silver nanoparticles (AgNp-Bio) reduce Toxoplasma gondii infection and proliferation in HeLa cells, and induce autophagy and death of tachyzoites by apoptosis-like mechanism
2021, Acta Tropica
Citation Excerpt :
Currently, the treatment of symptomatic toxoplasmosis consists of the combination of pyrimethamine and sulfadiazine, which act synergistically in blocking the pathway of folate synthesis, essential for the survival and replication of the parasite (Anderson, 2005). However, these drugs are highly toxic and require the concomitant use of folinic acid in order to reduce side effects, such as bone marrow suppression that can cause megaloblastic anemia, leukopenia, and granulocytopenia (Petersen, 2007; Serrano et al., 2016). Therefore, due to the difficulties faced in the current treatment of toxoplasmosis, the search for new therapeutic alternatives, that are more effective and less toxic to the patient, becomes necessary.
Toxoplasma gondii is a protozoan parasite that can cause severe and debilitating diseases, especially in immunocompromised individuals. The available treatment is based on drugs that have low efficacy, high toxicity, several adverse effects, and need long periods of treatment. Thus, the search for therapeutic alternatives is urgently needed. Biogenic silver nanoparticles (AgNp-Bio) have been associated with several biological effects, as antiproliferative, pro-apoptotic, antioxidant, antiviral, antifungal, and antiprotozoal activity. Thus, the objective was evaluating AgNp-Bio effect on HeLa cells infected with T. gondii (RH strain). First, nontoxic AgNp-Bio concentrations for HeLa cells (1.5 – 6 µM) were determined, which were tested on cells infected with T. gondii. A significant reduction in infection, proliferation, and intracellular parasitic load was observed, also an increase in ROS and IL-6. Additionally, the evaluation of the action mechanisms of the parasite showed that AgNp-Bio acts directly on tachyzoites, inducing depolarization of the mitochondrial membrane, ROS increase, and lipid bodies accumulation, as well as triggering an autophagic process, causing damage to the parasite membrane, and phosphatidylserine exposure. Based on this, it was inferred that AgNp-Bio affects T. gondii by inducing immunomodulation and microbicidal molecules produced by infected cells, and acts on parasites, by inducing autophagy and apoptosis.

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Toxoplasmosis

Summary

Section snippets

Prevalence of infection with Toxoplasma gondii

T. gondii infection in pregnancy

Risk factors for infection with T. gondii

T. gondii genotypes, distribution and pathogenicity

Diagnosis of T. gondii infections in pregnant women

Diagnosis of fetal infection

Diagnosis of T. gondii infection in live-born neonates

Systematic screening for T. gondii infection during pregnancy

Prevention of clinical signs and symptoms in newborns with congenital T. gondii infections identified by neonatal screening

No screening policy

Postnatal treatment

Treatment of symptomatic, congenital T. gondii infection

New drugs

Side effects from treatment and chemoprophylaxis

Drug resistance in T. gondii

Vet Parasitol

Clin Microbiol Infect

Microb Infect

Am J Ophthalmol

Am J Obstet Gynecol

Clin Microbiol Infect

Clin Microbiol Infect

Lancet

Lancet

Presse Med

Am J Ophthalmol

Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden

Epidemiol Infect

Incidence of Toxoplasma gondii infection in 35,940 pregnant women in Norway and pregnancy outcome for infected women

J Clin Microbiol

A model of toxoplasmosis incidence in the UK: evidence synthesis and consistency of evidence

J R Stat Soc Ser C Appl Stat

Toxoplasma gondii infection in the United States, 1999-2000

Emerg Infect Dis

Racial and ethnic differences in the seroprevalence of 6 infectious diseases in the United States: data from NHANES III, 1988-1994

Am J Public Health

Highly endemic, waterborne toxoplasmosis in north Rio de Janeiro state, Brazil

Emerg Infect Dis

Prevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis in non-haemophiliac HIV-1-infected adults in Taiwan

Int J STD AIDS

Incidence and prevalence of toxoplasmosis in Indian pregnant women: a prospective study

Am J Reprod Immunol

Toxoplasmosis: prevalence and risk factors

J Obstet Gynaecol

Toxoplasmosis in pregnant Sudanese women

Saudi Med J

Toxoplasma serology in HIV infected patients and suspected cerebral toxoplasmosis at the Central Hospital of Bobo-Dioulasso (Burkina Faso)

Bull Soc Pathol Exot

Incidence of symptomatic toxoplasma eye disease: aetiology and public health implications

Epidemiol Infect

Sources of Toxoplasma gondii infection in pregnancy. Until rates of congenital toxoplasmosis fall, control measures are essential

Br Med J

Risk factors for Toxoplasma gondii infection in pregnancy. Results of a prospective case-control study in Norway

Am J Epidemiol

Risk factors for recent toxoplasma infection in pregnant women in Naples

Epidemiol Infect

Buffolano W et al. Sources of toxoplasma infection in pregnant women: European multicentre case–control study. European Research Network on Congenital Toxoplasmosis

Br Med J

Choices in preventive strategies: experience with the prevention of congenital toxoplasmosis in The Netherlands

Scand J Infect Dis

Preventing congenital toxoplasmosis

MMWR Recomm Rep

Virulent strains of Toxoplasma gondii comprise a single clonal lineage

Nature

Unusual abundance of atypical strains associated with human ocular toxoplasmosis

J Infect Dis

Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii

Nucleic Acids Res

Genetic analysis of natural recombinant Brazilian Toxoplasma gondii strains by multilocus PCR-RFLP

Infect Genet Evol

Genetic divergence of Toxoplasma gondii strains associated with ocular toxoplasmosis, Brazil

Emerg Infect Dis

Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical findings

J Infect Dis

Determination of genotypes of Toxoplasma gondii strains isolated from patients with toxoplasmosis

J Clin Microbiol

Serotyping of Toxoplasma gondii infections in humans using synthetic peptides