Genome sequences of the first two imported cases of monkeypox detected in Kerala clearly show that they belong to a small cluster — A.2 — that was very different from the one that was first detected in the U.K. on May 6 this year and has since spread to more than 75 countries. The genomes from the major outbreak of monkeypox cases in Europe and the rest of the world belong to the B.1 lineage.
The genomes of the virus collected from the first two cases in Kerala were sequenced by ICMR’s nodal lab, National Institute of Virology, Pune and deposited without delay in the global database GISAID.
Two distinct outbreaks
In the first week of June, the CDC found that three of the 10 genomes sequenced from viruses collected in the U.S. were different from the viruses sequenced in Europe. The genetic sequences of monkeypox cases strongly suggested that there were two distinct monkeypox outbreaks outside the endemic countries in Africa. The two distinct clusters indicated that human-to-human transmission outside Africa was taking place for a longer time than what was assumed initially. The small cluster predominantly seen in the U.S., Thailand and now in India is the A.2 cluster.
All the three imported cases detected in Kerala were in men who had arrived from the Middle East. Writing in STAT, Helen Branswell noted that the three genomes from the viruses collected in the U.S. that belonged to the A.2 cluster were in people who had got infected from different parts of the globe — one in Nigeria, one elsewhere in West Africa, and the third in either the Middle East or East Africa.
Based on the wide geographical spread of the virus belonging to the A.2 cluster, Inger Damon, director of CDC’s division of high-consequence pathogens and pathology told STAT that the virus has been silently spreading outside the endemic countries for a longer time.
While all the three imported cases detected in Kerala were in people who had arrived from the Middle East, some of the cases detected elsewhere and falling in this cluster too are from people who have a travel history to Middle East or East Africa.
Superspreader events
The large outbreak that began in Europe in early May this year and since grown to over 21,000 cases globally has been spreading primarily through human-to-human transmission. The sustained transmission among humans has predominantly been among men who have sex with men (MSM) and had spread across Europe in a matter of few days due to two superspreader events. The small A.2 cluster is starkly different from the large B.1 cluster that represents the virus that began spreading in Europe.
According to Dr. Vinod Scaria, a senior scientist at the Delhi-based Institute of Genomics and Integrative Biology (CSIR-IGIB), the small A.2 cluster containing very few genomes and dating back to July 2021 does not show signs of being spread by any superspreader event.
“The earliest sample in the cluster from the U.S. is indeed from 2021 suggesting the virus has been in circulation for quite some time, and earlier than the European events,” Dr. Scaria tweeted.
“The A.2 seems to have a quite distinct origin and is unrelated to the large outbreak in Europe,” Dr. Scaria told The Hindu. “The A.2 cluster has a long tail suggesting that it originated quite some time ago. The virus belonging to the A.2 cluster was possibly spreading silently. But there are no intermediate genomes [sequenced at regular and short intervals between July 2021 and early June 2022] available, though.”
Considering that the A.2 cluster found in the U.S. and now in India is very small with only a handful of genomes, it is possible that the spread of the virus belonging to the A.2 cluster was not present in the MSM network; the B.1 lineage is predominantly found in the MSM networks. It is based on the premise that had A.2 cluster also been found in the MSM networks, then the number of people infected with the virus of A.2 cluster and the geographical spread would have been comparable with the B.1 lineage.
Dr. Scaria, however, cautions about drawing such conclusions based on a few samples sequenced. “The A.2 cluster could have been found in the MSM networks but wouldn’t have spread as widely as the B.1 lineage due to the absence of any superspreader events,” he says. “It is too early to draw any conclusions as we don’t have sufficient information from genome sequences.”
The U.S. leading in cases
As of July 28, 4,907 monkeypox cases have been detected in the U.S., by far the highest number for any country. And 37 countries in Europe have altogether reported 13,043 cases of monkeypox as of July 26.
Based on the results of a case series in the U.K. published in The BMJ on July 28, nearly 99% of cases are restricted to the MSM networks with sexual contact with an infected person being the prime driver of virus spread. And a significant proportion of cases are people with HIV.
“Although the outbreak is concentrated in MSM at this time, as case numbers increase, we will see cases in other demographic groups. There have been cases in children and women albeit few comparatively so far. This is why it is so important to act quickly to contain this,” Dr. Boghuma Titanji from the Emory University School of Medicine, Atlanta, tweeted. That said, there has so far not been any case of onward transmission among people outside the MSM networks.
Arguing that monkeypox virus is not highly transmissible compared with SARS-CoV-2 virus and the fact that it requires close, intimate contact to spread from one person to person, Dr. Francois Balloux from the UCL Genetics Institute tweeted that the virus can only maintain itself in demographics where people have many sexual partners, such as MSM networks.
“Monkeypox virus is not a pathogen that has the potential to become an STD in the heterosexual population. The reason is that those infected can pass it on effectively to others for no longer than about four weeks, and afterwards clear it, and become essentially immune for life,” he tweeted.
However, Dr. Titanji disagrees. “I do not agree that transmission facilitated through sex cannot happen in the heterosexual population. It certainly can and is probably happening though in may not be as sustained as in more dense sexual networks which have higher numbers of contacts,” she tweeted.
Increasing risk
While scientists debate whether the virus can spread in the heterosexual population and to what extent, it is abundantly clear that longer the virus continues to circulate and infect a greater number of people, the virus will gain the ability to become more transmissible and evolve to spread more easily through multiple routes.
