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Cryptosporidium Becoming More Virulent Due to Globalization And Animal Contacts

The parasites that cause cryptosporidiosis are evolving to become more virulent, warn an international team of researchers led by the University of East Anglia (UEA), in collaboration with scientists in Italy and Australia.

The team used whole genome sequence analysis to compare 32 sequences from human- and ruminant-derived parasite isolates of Cryptosporidium parvum collected across Europe, US, Egypt, and China. These comprised 22 newly sequenced isolates from humans and young ruminants across European genomes and 10 published genomes from previous studies.

The results, published in Molecular Ecology, found that different lineages are increasingly exchanging their DNA - indeed the team estimated that they have exchanged more DNA in the last 200 years than in all the time before that.

Evolving More Quickly

This speed, they said, meant that Cryptosporidium is evolving more quickly, potentially resulting in more virulent and better-adapted strains. They said that their results suggest that increased globalization and close human-animal contacts increased the opportunity for genetic exchanges between previously isolated parasite lineages, resulting in spill-over and spillback events.

The parasite, which is a major cause of diarrhoeal disease in both humans and ruminants, is responsible for around 57,000 human deaths each year, 80% of which are among children aged under 5 years. Routes of transmission are most often by direct contact with infected animals or humans. Transmission can also be indirect, for example via recreational waters such as swimming pools or occasionally via food or water.

In the UK, this was reported by Public Health England typically reports 3000 – 6000 cases of cryptosporidiosis annually in England and Wales until 2019, mainly associated with petting farms, drinking or swimming in contaminated water, and sometimes food-borne outbreaks.

No Effective Drug or Vaccine Available

Joint senior author of the new study, Cock Van Oosterhout, professor of evolutionary genetics at the UEA’s School of Environmental Sciences, said: "Cryptosporidium is an important genus of zoonotic parasites, and it is one of several microorganisms that cause diarrhoeal disease in both humans and some livestock. The vast majority of these are in low-income countries, but outbreaks also occur in the UK and elsewhere in Europe. There is no effective drug or vaccine available, so understanding the transmission and evolution of this parasite is critical.

"We know that there are several lineages of the Cryptosporidium parvum parasite, but we wanted to understand more about how they evolve, and particularly, why this species may be becoming more virulent than it was in the past."

The authors explained that the parasite's life cycle comprises an obligatory sexual phase, during which genetic exchanges can occur between previously isolated lineages. They identified three strongly supported clusters that comprise a mix of isolates from different host species, geographic origins, and subtypes. They demonstrated that:

  • Recombination occurs between ruminant isolates into human isolates
  • These recombinant regions can be passed on to other human subtypes through gene flow and population admixture
  • There have been multiple genetic exchanges, and most are probably recent
  • Putative virulence genes are significantly enriched within these genetic exchanges
  • This results in an increase in their nucleotide diversity

To examine whether the rate of genetic exchanges might have increased only recently, the team calculated the cumulative percentage of recombinant nucleotides against the age of the recombination event. This showed that about 22% nucleotides had been exchanged between the three lineages in the last 200 years. They reasoned that if the historic rate of recombination had been as high as that of the past 200 years, then the three lineages would have been homogenized, and they would not appear genetically distinct. "This suggests that the rate of genetic exchanges has increased in the past two centuries," they said.

Genetic Exchanges Particularly Affect Genes Involved in Virulence

They explained that the long-term evolutionary consequences of these events "provide a novel substrate for natural selection at genes involved in host–parasite interactions, thereby potentially altering the dynamic co-evolutionary equilibrium in the Red Queen’s arms race". This is a geneticists' hypothesis – named after a character in Alice in Wonderland who must keep running on the spot to stay in the same place - that where species compete for limited resources, evolution-by-natural-selection means that when one species evolves an advantageous adaptation, a competing species must respond in kind or fail as a species: it cannot stand still.

Prof Van Oosterhout said: "We found that different lineages of these parasites are increasingly exchanging their DNA. In the last 200 years, around 22% of the genome of these parasites has been exchanged. This is significantly more than the DNA they have exchanged in all the time before. The genes that are involved in virulence seem to be particularly affected by such genetic exchanges." These helped Cryptosporidium to evolve more quickly, resulting in more virulent and better-adapted human parasites.

"This is really important because, as COVID-19 has shown us, human parasites can evolve rapidly. We hypothesise that the rate of evolution is further accelerated because the parasite can evolve in multiple host species. This means that novel adaptations that have evolved in parasites that infect one host species can now be used by parasites that infect another species of hosts."

Indeed, the team found that the genome of parasites that infect humans possess some DNA of parasites normally found in cows and lamb. "The increased connectivity in our globalised world and close contact between humans and domesticated animals increases the rate of spill-over and spillback events," Prof Van Oosterhout said.

"Using whole genome sequence analysis, we can now study these genetic exchanges and identify when and where they are taking place. This will help us better control these emerging infectious diseases of zoonotic parasites and pathogens."