Jeroen Saeij

Toxoplasmosis

Why the same parasite is mild in Europe and severe in South America

Ask what toxoplasmosis does to people and the honest answer is that it depends which Toxoplasma. This has been the central question of my own research for twenty years.

By Jeroen Saeij · Updated 17 September 2026

The short answer

In Europe and North America, three closely related clonal types account for most infections, and one of them, type II, causes most human cases, usually mild. In South America the parasite is genetically diverse, and some strains cause severe disease in healthy adults and eye disease at rates unheard of elsewhere. We understand in detail why some strains kill mice; we understand much less about what makes them dangerous to people.

A parasite with two population structures

In 1995 a survey of parasite isolates from Europe and North America found something unusual for a sexually reproducing organism: nearly all of them belonged to three clonal lineages, named types I, II and III, and most human cases were type II1. Later work with better markers confirmed that a handful of genotypes dominate the northern hemisphere. The southern hemisphere is another world. Among 1,457 typed samples, 189 genotypes were found, and in Central and South America no single genotype dominates: hundreds coexist2.

Comparing 62 genomes from around the world showed what the differences are made of. The genes that vary most between strains are the ones for secreted proteins that the parasite injects into the host cell, and these are arranged in amplified, diversified clusters inherited in large blocks3. In other words, what distinguishes strains is precisely the toolkit they use to manipulate their hosts.

What that means for people

Severe disease in healthy adults. In French Guiana, sixteen otherwise healthy adults were hospitalized over six and a half years with severe acute toxoplasmosis, most with lung involvement. Nearly all had eaten game meat, and the strains isolated from them were atypical genotypes never seen in Europe4.

Eye disease. In a town in southern Brazil, a household survey found eye lesions from toxoplasmosis in 17.7 percent of the population, more than thirty times the rates reported elsewhere5. When children with congenital toxoplasmosis in Brazil and Europe were followed with the same protocol, half of the Brazilian children had eye lesions in their first year against one in ten in Europe, and their disease was more severe6.

Reinfection. Immunity built against a European strain does not necessarily protect against a South American one. A French mother who was immune before conception transmitted an atypical strain to her baby after eating imported raw horse meat7. My lab showed in mice that prior infection protects against the standard laboratory strain but not against most strains circulating in South America8.

Wildlife. The same principle plays out along the California coast, where sea otters die of toxoplasmosis. Most infected otters carry an unusual lineage called type X, and the strains that kill them can be traced to wild and domestic cats in nearby watersheds9. A rare strain called COUG has recently caused a cluster of fatal infections with severe inflammation of the body fat10.

What makes a strain dangerous

This is where my lab has spent most of its effort, and where I have to be careful about the difference between mice and people.

In mice, we know a great deal. As a postdoc I helped show that the difference between a strain that kills a mouse and one that does not comes down to a few secreted enzymes, the rhoptry kinases, and that a single one of them, ROP18, can turn a mild strain lethal11. Another, ROP16, is injected into the host cell nucleus, where it switches host genes on and off12. Together with the pseudokinase ROP5, ROP18 works by disabling the mouse’s most important weapon against the parasite, a set of interferon-induced proteins that destroy the vacuole the parasite lives in.

Here is the catch. Those mouse weapons are not the ones human cells rely on. In human cells, ROP18 and ROP5 make no difference to the parasite’s survival13, so the factors that explain virulence in mice do not explain why South American strains are so much worse in people. Something else in the parasite’s toolkit must be responsible, and finding it is what much of my lab’s current work in human cells is about. Until then, the honest statement is that we can tell which strains are dangerous, and we can only partly say why.

What this means for you

If you live in, or travel to, South America and eat rare meat or game, the precautions on the food and water page matter more than they do in Europe or North America, and they matter even if you were infected before. If you have unexplained eye symptoms after such travel, mention toxoplasmosis to your eye doctor. And if you are a scientist wondering why a parasite study in mice did not translate, this parasite is a lesson in why the host species matters.

Sources

  1. Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 1995;172:1561-6. PubMed · DOI
  2. Shwab EK, Zhu XQ, Majumdar D et al. Geographical patterns of Toxoplasma gondii genetic diversity revealed by multilocus PCR-RFLP genotyping. Parasitology 2014;141:453-61. PubMed · DOI
  3. Lorenzi H, Khan A, Behnke MS et al. Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nat Commun 2016;7:10147. PubMed · DOI
  4. Carme B, Bissuel F, Ajzenberg D et al. Severe acquired toxoplasmosis in immunocompetent adult patients in French Guiana. J Clin Microbiol 2002;40:4037-44. PubMed · DOI
  5. Glasner PD, Silveira C, Kruszon-Moran D et al. An unusually high prevalence of ocular toxoplasmosis in southern Brazil. Am J Ophthalmol 1992;114:136-44. PubMed · DOI
  6. Gilbert RE, Freeman K, Lago EG et al. Ocular sequelae of congenital toxoplasmosis in Brazil compared with Europe. PLoS Negl Trop Dis 2008;2:e277. PubMed · DOI
  7. Elbez-Rubinstein A, Ajzenberg D, Dardé ML et al. Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review. J Infect Dis 2009;199:280-5. PubMed · DOI
  8. Jensen KD, Camejo A, Melo MB et al. Toxoplasma gondii superinfection and virulence during secondary infection correlate with the exact ROP5/ROP18 allelic combination. mBio 2015;6:e02280. PubMed · DOI
  9. Shapiro K, VanWormer E, Packham A et al. Type X strains of Toxoplasma gondii are virulent for southern sea otters (Enhydra lutris nereis) and present in felids from nearby watersheds. Proc Biol Sci 2019;286:20191334. PubMed · DOI
  10. Sinnott DM, Miller M, Arranz-Solís D et al. Fatal Toxoplasma gondii COUG strain infections in southern sea otters (Enhydra lutris nereis): New insight on contributing factors and parasite serotyping. PLoS One 2025;20:e0332223. PubMed · DOI
  11. Saeij JP, Boyle JP, Coller S et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 2006;314:1780-3. PubMed · DOI
  12. Saeij JP, Coller S, Boyle JP et al. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 2007;445:324-7. PubMed · DOI
  13. Niedelman W, Gold DA, Rosowski EE et al. The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response. PLoS Pathog 2012;8:e1002784. PubMed · DOI