A global team of scientists has discovered a genetic variant in the Inuit that may be responsible for worse outcomes than viral infections.
People with the gene deficiency fail to produce certain types of interferon, which are proteins that fight infection. This can lead to severe illness when encountering certain viruses, such as measles, influenza, or COVID-19.
“If you have this variant, you are going to have a problem with viruses,” said Trine Mogensen, a biomedical researcher at Aarhus University in Denmark and lead author of the study. Published in the Journal of Experimental Medicine.
“It’s a huge risk factor.”
The findings are the result of a global network of researchers who studied five Inuit children from Canada, Greenland and Alaska who were hospitalized with an unusually severe viral infection.
In two of the cases, children with troublesome infections were hospitalized with severe colds. But doctors have found that few treatments have been effective, and usually harmless childhood vaccinations seem to make matters worse.
As their condition worsened, doctors discovered they had tested positive for not one but several viral infections, from Epstein-Barr to chickenpox.
Two other cases involved children who developed high fevers and seizures within a few weeks of receiving the common children’s measles, mumps and rubella (MMR) vaccine, which contains a weakened version of the virus. While both recovered, one later died of COVID-19 infection – which is very unusual in young children. The sister of one of these patients became very ill with the flu, although she was able to receive the MMR vaccine without incident.
The researchers suspected that there might be an underlying genetic explanation for why these children had such unusually severe responses to common childhood viruses. When the children were tested, they found a previously undocumented genetic variant which meant these children were worse equipped to fight off infectious diseases.
1 in 1500 affected Inuit
The researchers then searched a database of more than 4,600 Greenlanders and just over 100 Inuit from 10 communities in Nonavik to see how common genetic deficiency is.
They estimate that one in 1,500 Eskimos is affected, putting them at risk of severe reactions to COVID-19, influenza and some common childhood vaccinations, because they cannot fight off many viruses.
In comparison, the gene is almost absent in other populations. The authors say that more testing should be done on the Inuit to determine how many people may be affected.
Michael Patterson, Nunavut’s chief medical officer of health, questioned the newspaper’s numbers, saying the study did not provide enough data to form a “firm or reliable estimate.” He said more genetic sampling among Canadian Inuits was needed to determine if “it is appropriate to begin screening for this condition.”
But other experts say the result is not surprising.
“I’m not surprised,” said Shirley Tagalik, president of the Akqiumavvik Wellness Association in Arviet, Nunavut, and a longtime community researcher in Inuit health. “We’ve known for several years that Inuit children in particular may react differently to different vaccines.”
Anna Banerjee, an expert in indigenous health, pediatrics and infectious diseases at the University of Toronto’s Dalla Lana School of Public Health, wasn’t surprised either. I have studied respiratory infections in Inuit children for decades and found that they occur almost Four times as often as in non-Inuiteven when controlling for environmental factors.
“I always thought there was a genetic component,” she said.
The researchers stressed that the vaccine does not lead to hesitation
One in 1500 sounds like a lot, but among the relatively small Inuit population, the number is about 100 Inuits worldwide, and about 50 in Canada.
For those few people, influenza or COVID-19 infection is likely to cause hospitalization or death. They are also at serious risk from live virus vaccines, such as the MMR and yellow fever vaccines, which use a weakened form of a particular virus to teach the body’s immune system how to respond when it encounters the real thing.
But experts stress that the findings should not make people wary of vaccines in general. First of all, many modern vaccines, such as the COVID-19 vaccine, do not carry live virus at all, and pose no risk to those who have the genetic variant.
“All other vaccinations in the Childhood Influenza and COVID-19 Program” are still safe for those with the gene to receive, Mogensen said.
Second, for those who do not have the variant – including the vast majority of Inuit – it is essential that live virus vaccinations continue. Childhood vaccinations, such as the measles, mumps and rubella vaccine, have been instrumental in reducing the severity of the disease in the north, which saw outbreaks of measles and tuberculosis a generation ago.
“Some communities became extinct because of these viruses,” Banerjee said. “The worst thing we can start saying is that we should not vaccinate Inuit children because of this danger.”
Patterson encouraged parents to stick to the routine vaccination schedule, and stressed that even using the population estimates given in the paper, “one child every two years or so” would be affected.
“Avoiding vaccines because of that, for the vast majority of people, will greatly increase their risk of severe infection.”
Sorting is possible, but elusive
As with many genetic disorders, it is possible to detect the deficiency before the baby is born, or along with tests for other disorders, such as cystic fibrosis, after the baby is born.
Mogensen says that children who test positive for this deficiency could be put on a course of antiviral medications that would protect them from the worst infections in childhood. she is Working with pediatricians in Denmark To implement one there as soon as possible.
But Patterson said it was impossible to say when the Nunavut Inuit could begin screening for deficiency.
Currently, newborns in Nunavut are automatically screened for a variety of genetic disorders, which occur, albeit rarely, in Inuit and non-Inuit alike. Labs testing for these disorders “may or may not be able to test easily for this disease,” Patterson said.
Mogensen and independent genetic testing laboratories contacted by CBC suggested otherwise. Aaron Goldman, chief scientific officer of DNALabs Canada, said it would cost “a maximum of two thousand dollars” to redesign the test, and about $100 per sample after that. Against the cost of medication and hospitalization, Mogensen describes the screening as “cost-effective.”
Banerjee suggested there was a “lack of political will” to address an issue affecting a small indigenous population.
“There is a systematic bias against indigenous people,” she said. “We are willing to find genetic testing for rare diseases where there is more lobby.”
Tagalik, a community health researcher in Arviat, said the paper provided a “mine field” to health authorities. Implementing a screening program, or even just collecting more data, will require “participation, commitment and approval from not just the people at the top and the people at the bottom, but all those people in between.”
In the past, it has seen its recommendations for childhood health falter due to government protests over cost, community leadership rotation, and objections from the medical establishment.
She said, “Nothing will move forward if you don’t have the government behind you, and even if you have the government backing you, it’s not enough.”
Unique among the Inuit
Although a genetic variant, known as IFNAR2 deficiency, has been documented only in Inuit, researchers have also found a similar variant, affecting the IFNAR1 gene, In western Polynesia In a parallel study.
Scholars attribute this commonality to the relatively isolated existence of these societies for much of their history. It may also be a reason why outbreaks of infectious diseases, such as measles and tuberculosis, have been so devastating to these communities.
“We think that some of these severe infections, which were thought to be meningitis or tuberculosis, may be caused by this defect,” Mogensen said.
Inuit have not often been the subject of genetic studies, in part because human genome mapping projects have historically focused on Caucasian populations.
“We have a biased map of the genome,” Mogensen said. “We’ve done genetic sequencing for no more than 20 years, and most… of the patients are white.”
But the researchers admit that getting more Inuit genetic data will be a serious challenge.
“Genetic testing can be a very disgraceful,” Patterson said. “It can lead to inappropriate medical responses, and it can lead to … undue fear, the feeling that by doing genetic testing, they have lost a little bit of physical independence.”
Tagalik, who is not herself an Inuit but her husband and children, says genetic studies of the Inuit are “a challenging area to work in for many reasons.”
With all health research in Nunavut, she said, “there has to be a commitment… to really work in the best interest of our communities.”
However, she said, the paper offers “indications that should be pursued.”
“We would be neglected and marginalized if no work was done to explore these preliminary findings in more detail, and in all Inuit jurisdictions,” she said.