Posts tagged brain infection
Articles and news from the latest research reports.
New virus isolated from patients with severe brain infections
Researchers have identified a new virus in patients with severe brain infections in Vietnam. Further research is needed to determine whether the virus is responsible for the symptoms of disease.
The virus was found in a total of 28 out of 644 patients with severe brain infections in the study, corresponding to around 4 per cent, but not in any of the 122 patients with non-infectious brain disorders that were tested.
Infections of the brain and central nervous system are often fatal, and patients who survive - often young children and young adults - are left severely disabled. Brain infections can be caused by a range of bacterial, parasitic, fungal and viral agents; however, doctors fail to find the cause of the infection in more than half of all cases, despite extensive diagnostic efforts. Not knowing the causes of these brain infections makes public health and treatment interventions impossible.
Researchers at the Oxford University Clinical Research Unit, the Wellcome Trust South East Asia Major Overseas Programme and the Academic Medical Center at the University of Amsterdam identified the virus, tentatively named CyCV-VN, in the fluid around the brain of two patients with brain infections of unknown cause. The virus was subsequently detected in an additional 26 out of 642 patients with brain infections of known and unknown causes.
Using next-generation gene sequencing techniques, the team sequenced the entire genetic material of the virus, confirming that it represents a new species that has not been isolated before. They found that it belongs to a family of viruses called the Circoviridae, which have previously only been associated with disease in animals, including birds and pigs.
Dr Rogier van Doorn, Head of Emerging Infections at the Wellcome Trust Vietnam Research Programme and Oxford University Clinical Research Unit Hospital for Tropical Diseases in Vietnam, explains: “We don’t yet know whether this virus is responsible for causing the serious brain infections we see in these patients, but finding an infectious agent like this in a normally sterile environment like the fluid around the brain is extremely important. We need to understand the potential threat of this virus to human and animal health.”
The researchers were not able to detect CyCV-VN in blood samples from the patients, but it was present in 8 out of 188 faecal samples from healthy children. The virus was also detected in more than half of faecal samples from chickens and pigs taken from the local area of one of the patients from whom the virus was initially isolated, which may suggest an animal source of infection.
Dr Le Van Tan, Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, said: “The evidence so far seems to suggest that CyCV-VN may have crossed into humans from animals, another example of a potential zoonotic infection. However, detecting the virus in human samples is not in itself sufficient evidence to prove that the virus is causing disease, particularly since the virus could also be detected in patients with other known viral or bacterial causes of brain infection.
"While detection of this virus in the fluid around the brain is certainly remarkable, it could still be that it doesn’t cause any harm. Clearly, we need to do more work to understand the role this virus may play in these severe infections."
The researchers are currently trying to grow the virus in the laboratory using cell culture techniques to develop a blood assay to test for antibody responses in patient samples, which would indicate that the patients had mounted an immune response against the virus. Such a test could also be used to study how many people in the population have been exposed to CyCV-VN without showing symptoms of disease.
The team are collaborating with scientists across South-east Asia and in the Netherlands to determine whether CyCV-VN can be detected in patient samples from other countries and better understand its geographical distribution.
Professor Menno de Jong, head of the Department of Medical Microbiology of the Academic Medical Centre in Amsterdam, said: “Our research shows the importance of continuing efforts to find novel causes of important infectious diseases and the strength of current technology in aid of these efforts.”
(Source: wellcome.ac.uk)
Brain displays an intrinsic mechanism for fighting infection
White blood cells have long reigned as the heroes of the immune system. When an infection strikes, the cells, produced in bone marrow, race through the blood to fight off the pathogen. But new research is emerging that individual organs can also play a role in immune system defense, essentially being their own hero. In a study examining a rare and deadly brain infection, scientists at The Rockefeller University have found that the brain cells of healthy people likely produce their own immune system molecules, demonstrating an “intrinsic immunity” that is crucial for stopping an infection.
Shen-Ying Zhang, a clinical scholar in the St. Giles Laboratory of Human Genetics of Infectious Diseases, has been studying children with Herpes simplex encephalitis, a life-threatening brain infection from the herpes virus, HSV-1, that can cause significant brain damage. The scientists already knew from previous work that children with this encephalitis have a genetic defect that impairs the function of an immune system receptor — toll-like receptor 3 (TLR3) — in the brain. For this study they wanted to see how the defect in TLR3 was hampering the brain’s ability to fight the herpes infection.
When TLR3 detects a pathogen it triggers an immune response causing the release of proteins called interferons to sound the alarm and “interfere” with the pathogen’s replication. It’s most commonly associated with white blood cells, found throughout the body, but here the researchers were examining the receptor’s presence on neurons and other brain cells.
“One interesting thing about these patients is that they didn’t have any of the other, more common herpes symptoms. They didn’t have an infection on their skin or their mouths, just in their brains. We therefore hypothesized that the TLR3 response must be specifically responsible for keeping the herpes virus from infecting the brain and not necessary in other parts of the body,” says Zhang.
The lab, headed by Jean-Laurent Casanova, collaborated with scientists at Harvard Medical School and Memorial Sloan-Kettering Cancer Institute to create induced pluripotent stem cells. Made from the patients’ own tissue, the stem cells were developed into central nervous system cells that carried the patients’ genetic defects. Zhang exposed the cells to HSV-1 and to synthetic double-stranded RNA, which mimics a byproduct of the virus that spurs the toll-like receptors into action. By measuring levels of interferon, Zhang showed that the patients’ TLR3 response was indeed faulty; their cells weren’t making these important immune system proteins, leaving them unable to fight off the infection.
Zhang also exposed the patients’ blood cells to the virus and found that the TLR3 defect was not an issue there as it was in the brain — interferons were released by other means.
Because the toll-like receptors on neurons proved to be vital in preventing the encephalitis infection, the researchers concluded that brain cells use it as an in-house mechanism to fight infection, rather than relying on white blood cells. When its function was impaired, patients couldn’t get better.
“This is evidence of an intrinsic immunity, a newly-discovered function of the immune system,” says Zhang. “It’s likely that other organs also have their own specific tools for fighting infection.”
The researchers are putting together a pilot study to test an interferon-based treatment in patients with the encephalitis, believing it will help speed recovery and increase the survival rate when used alongside antiviral drugs. They’ll also explore whether the brain displays an intrinsic immunity to other types of viral infection.