Daily Archives: November 22, 2014

Researchers have succeeded in sequencing the genome of a rare tapeworm that resided in the brain of a British man for four years.

There have only been 300 reports of the worm, known as Spirometra erinaceieuropaei, since 1953 and it has never appeared in the UK before. As the parasite is so rare it is not known exactly how it entered the man's body, although it is possible that it could have been caused by the man consuming tiny crustaceans from lakes, eating raw meat from amphibians and reptiles or by using a raw frog poultice, which is a Chinese remedy to cause sore eyes.

Although the man is now systemically well now, the worm causes sparganosis in humans, which is an inflammation of bodily tissues. When the parasite is inside the brain this can cause seizures, memory loss and headaches.

In this case, the worm in the man's brain was found to be only 1cm long, but before it was diagnosed and removed, it had travelled 5cm from the right side of the brain to the left. It took four years of eliminating other diseases, followed by regular MRI scans to discover what was causing the man's headaches and seizures. Comparing the MRI scans, it is possible to see the worm travelling slowly across the brain.

Even when the parasite was spotted, it wasn't possible to identify it as Spirometra erinaceieuropaei. "The key thing in this case was that the pathologist recognised it was a parasite," Matt Berriman tells WIRED.co.uk. It was removed using precision surgery and placed on a histology slide. "They pulled it out essentially with a biopsy needle."

Researchers then had to go about identifying the worm. This took several months -- and not just because we're not used to seeing such parasites in the UK. Even in countries like China and Korea where the parasite originates, it is so rare that there is very little information known about it.

"The clinical histology slide offered us a great opportunity to generate the first genome sequence of this elusive class of tapeworms," says Hayley Bennett from the Wellcome Trust Sanger Institute. Bennett, who was first author of the study detailing the genetic findings from the parasite, points out that because they only had a very tiny piece of DNA to work with -- "just 40 billionths of a gram" -- they had to make some very tough calls about exactly they wanted to find out from the DNA.

In all creatures there is one particular gene known as "the barcode of life" that can be sequenced in order to determine the exact species of the animal. When they did this to the parasite, the researchers discovered that it was a Spirometra erinaceieuropaei worm, and that of the two known sparganosis-causing worm species, the one in the man's brain was the more benign of the pair.

They also managed to generate sufficient DNA sequence data to put together a draft genome, which is now being used to investigate known and potential treatment targets.

"We made a couple of sequencing libraries -- one was very good," says Berriman. This was enough to piece together the draft genome quite nicely. He admits though that "this is not a good example about how to build a genome". Ideally to make a reference genome you wouldn't need to use a histology slide at all, he says.

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Genome of man's rare brain worm detailed in online 'WormBase'

FRIDAY, Nov. 21, 2014 (HealthDay News) -- Scientists say they've mapped the genome -- the genetic "blueprint" -- of a tapeworm extracted from a British man's brain, in hopes it might help others with this very rare infection.

As reported Nov. 21 in the journal Genome Biology, the tapeworm was removed from the brain of a 50-year-old British man of Chinese ethnicity.

"This infection is so rare worldwide and completely unexpected in this country that the patient was not diagnosed ... until the worm was pulled out from the brain," study lead author Hayley Bennett, of the Wellcome Trust Sanger Institute in the United Kingdom, said in a journal news release.

As the researchers explained, most tapeworms live in the gut, causing symptoms such as weight loss, weakness and abdominal pain. However, some species travel to areas such as the eyes, spinal cord and brain.

In this study, researchers sequenced the genome of a 1-centimeter larval tapeworm removed from the man's brain. He had been complaining of symptoms such as headaches, seizures, altered smell and memory problems. The man survived the surgery and is recovering, Bennett's team said.

Through sequencing the tapeworm's genome, researchers identified it as a rare species called Spirometra erinaceieuropaei, typically found in China, Japan, South Korea and Thailand. Infection can occur when a person eats undercooked frogs or snakes, uses frog meat for treating wounds, or drinks contaminated water.

The researchers believe the gene study might lead to improved drug treatment for people with the parasite. By sequencing the tapeworm's genome, they pinpointed genes that provide resistance to a drug called benzimidazole, and other genes that suggest a possible sensitivity to another tapeworm drug, praziquantel.

The researchers also identified a number of genes that may offer targets for drugs that are already on the market but used to treat other conditions.

"We were also surprised at how large the genome was; it is much bigger than those of other known flatworms, and roughly a third of the size of the human genome," Bennett said.

"By comparing the genome to other tapeworms we can see that certain gene families are expanded -- these possibly underpin this worm's success in a large variety of host species," she added. "The data gave us a first look at a whole group of tapeworms that have not been sequenced before."

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Ick! Tapeworm infecting man's brain yields genetic secrets

A genome of a rare species of tapeworm found living inside a patient's brain has been sequenced for the first time, in research published in the open access journal Genome Biology. The study provides insights into potential drug targets within the genome for future treatments.

Tapeworms are parasites that are most commonly found living in the gut, causing symptoms such as weakness, weight loss and abdominal pain. However, the larvae of some species of tapeworm are able to travel further afield to areas such as the eyes, the brain and spinal cord.

A 50-year-old man of Chinese ethnicity was admitted to hospital in the East of England after reporting symptoms of headaches, seizures, altered smell and memory impairment. The patient had lived in the UK for 20 years but visited his homeland often. After testing negative for a range of diseases and not presenting any other abnormalities, doctors began to take a series of MRI images of his brain. Over the course of four years, they noticed a lesion migrate at least 5 cm across his brain, and after taking a biopsy from his left thalamus, they discovered a 1 cm long ribbon-shaped larval worm. The patient, who remains anonymous, was cured of his infection by the operation and is now recovering.

Small samples of the worm were sent to researchers at the Wellcome Trust Sanger Institute, where they began to investigate its genome. Through sequencing its DNA, they identified it as Spirometra erinaceieuropaei, a rare tapeworm species typically found in China, South Korea, Japan and Thailand, and known to cause infection by ingesting undercooked frogs or snakes, using frog meat for treating wounds, and ingesting contaminated water.

The researchers sequenced the worm's entire genome for the first time, measuring it as 1.26 billion base pairs long, which is currently the largest reported genome for any flatworm. This was despite the fact they had such a small sample to work from after removal from the patient's brain. By investigating specific sections of the worm's genome, they were also able to identify genes for resistance to certain treatments, and other potential drugs targets.

Lead author Hayley Bennett from the Wellcome Trust Sanger Institute said: "This infection is so rare worldwide and completely unexpected in this country that the patient was not diagnosed with sparganosis until the worm was pulled out from the brain. We were also surprised at how large the genome was, it is much bigger than those of other known flatworms, and roughly a third of the size of the human genome. By comparing the genome to other tapeworms we can see that certain gene families are expanded -- these possibly underpin this worm's success in a large variety of host species. The data gave us a first look at a whole group of tapeworms that have not been sequenced before."

Through investigating specific parts of the genome for sensitivity to known tapeworm treatments, the researchers found that the tapeworm had genes providing resistance to benzimidazole, but possible sensitivity to another tapeworm drug praziquantel.

The team also investigated the genome to find potential targets which could be exploited by drugs already on the market but known for treating other diseases. They found a number of genes which are targets for known cancer drugs, suggesting that these treatments could be re-purposed for treating this type of infection.

The researchers also identified twenty expanded gene families with unknown function, which they say demonstrates how little is known about this order of tapeworms, and could explain its ability to live in a wide range of hosts (crustaceans, reptiles, amphibians and mammals) as well as in aquatic environments. They have made all their data publicly available so as to help other researchers.

Hayley Bennett said: "We think that it is important to make the genomic data available as is it offers a resource predicting whether other drugs can be repurposed for use in really rare infections such as in this case."

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Tapeworm found living inside a patient's brain: Worm removed and sequenced