Toxoplasmosis in Germany

Abstract

Background: With approximately 30% of the world population infected, Toxoplasma gondii is one of the most widespread pathogenic parasites in both humans and animals and a major problem for health economics in many countries.

Methods: This review is based on the findings of individual studies, meta-analyses, and Cochrane Reviews retrieved by a selective literature survey of the Medline and Google Scholar databases.

Results: Current data indicate a high rate of Toxoplasma gondii infection in Germany, ranging from 20% to 77% depending on age (95% confidence interval for 18- to 29-year-olds [17.0; 23.1]; for 70- to 79-year-olds [72.7; 80.5]). Male sex, caring for a cat, and a body mass index of 30 or more are independent risk factors for seroconversion. Postnatally acquired (food-related) infec- tion is predominant, but maternal-to-fetal transmission still plays an important role. While most infections are asymptomatic, congenital toxoplasmosis and reactivated Toxoplasma encephalitis in immunosuppressed persons (transplant recipients and others) are sources of considerable morbidity. Toxoplasma gondii infection of the retina is the most common cause of infectious uveitis in Germany. The diagnosis and treatment of this type of parasitic infection are particular to the specific organs involved in the individual patient.

Conclusion: Desirable steps for the near future include development of an effective treatment for the cystic stage and identifica- tion of biomarkers to assess the risk of reactivation and predict the disease course.

Figure 1

T. gondii infection cycle (simplified). The infective pathogen is transmitted in the form of oocysts (spores) excreted in the feces of infected cats (1). Thus, T. gondii can be transmitted to domestic animals and rodents as well as to humans via contaminated food (2). Cats acquire the infection via tissue cysts (bradyzoites = chronic, slowly multiplying stage of the parasite) when they eat, for example, infected rodents (3). The same occurs in humans through consumption of undercooked meat from infected animals (3). Transplantation of tissue from infected persons (4) and diaplacental transmission (5) during a first infection in a pregnant woman are additional routes of infection. The acute, rapidly replicating intracellular tachyzoite stage spreads within infected organisms before transforming into bradyzoites (adapted from [e3]).

Figure 2

The seroprevalence of T. gondii in the federal states of Germany in 2008 (left) and cumulative data on T. gondii-related diagnoses for the period 2000 to 2016 (right). The markedly higher seroprevalence in the eastern part of the country is probably due to the much higher consumption of raw pork mince and raw sausage in those states (5), as has been observed for other infectious diseases transmitted through the consumption of meat (e.g., yersiniosis) (e8, e9). Based on the analysis of hospital data on diagnoses (per 1 million head of population) from 2000 to 2016 (available at www.gbe-bund.de), using the ICD-10 four-digit codes for toxoplasmosis (B58), it can be seen that billing figures are also much higher in the eastern states. It may be concluded from this that the higher seroprevalence in eastern Germany appears to be accompanied by a higher disease burden in these states. BE, Berlin; BR, Brandenburg; BW, Baden–Württemberg; BY, Bavaria; HB, Bremen; HE, Hesse; HH, Hamburg; MV, Mecklenburg–West Pomerania; NI, Lower Saxony; NW, North Rhine–Westphalia; RP, Rhineland–Palatinate; SH, Schleswig–Holstein; SL, Saarland; SN, Saxony; ST, Saxony–Anhalt; TH, Thuringia

Figure 3

Retinal image of a 27-year-old woman with recurrent ocular toxoplasmosis in the right eye. Retinal necrosis can be seen above the macula, with a fresh recurrence (central “fluffy” focus) surrounded by two older, pigmented lesions. Visual acuity is reduced to 0.63, with a deep, irreversible paracentral visual field defect (Department of Ophthalmology, Charité Campus Virchow, University Faculty of Medicine, Berlin).

eFigure

Simplified representation of dissemination and immune response in T. gondii infection. Once oral infection has occurred, T. gondii penetrates the intestinal epithelium and becomes disseminated, in part intracellularly, in dendritic cells and macrophages in the host and infects many organs. In the gut, macrophages and dendritic cells recognize intracellular tachyzoites and/or conserved structural features of the parasite (e.g., glycosylphosphatidylinositol, parasitic DNA and RNA) by means of toll-like receptors (TLR9) and other pattern-associated recognition receptors. The activated macrophages and dendritic cells produce IL-12, which induces interferon-? production of natural killer (NK) cells and type 1 innate lymphoid cells. Alongside this activation of the innate immune system, parasite-specific CD4⁺ and CD8⁺ T cells develop, which also produce IFN-γ and are activated by dendritic cells and/or macrophages. IFN-γ induces antiparasitic effector mechanisms in infected cells, such as production of GTPases and indoleamine-2,3-dioxygenase. Likewise, the cytotoxic effect of NK and CD8⁺ T cells contributes to the elimination of infected cells. Through the production of IL-4, T cells activate B cells, which contribute to protection by producing T. gondii-specific antibodies.