Chikungunya: Where did the virus really come from?

N. Gopal Raj
The Hindu, 27 November

The disease is believed to have originated in Africa where forest-dwelling mosquitoes circulate the virus among wild non-human primates.

In the space of two years, chikungunya has gone from being a disease known principally to medical specialists to becoming a much-dreaded pestilence that, even if it doesn’t kill, leaves sufferers often enduring months of crippling pain.

Starting in early 2005, this disease, which is caused by a virus spread by mosquitoes, swept through the islands of Comoros, Mayotte, Seychelles, Reunion and Mauritius that lie in the south-western Indian Ocean, not far from the coast of Africa. The epidemic continued into 2006.

From late 2005 onwards, hospitals in Andhra Pradesh, Karnataka and Maharashtra found themselves swamped with patients complaining of fever and joint pain, which turned out to be chikungunya. Large numbers of people fell victim to the virus in these States during 2006, and the disease spread to other parts of the country as well. The statistics on the website of the Union Government’s National Vector Borne Disease Control Programme show that some 1.4 million people in the country may have contracted the disease in 2006.

From Kerala to Italy

Kerala continued to reel from the disease this year as well, and cases of chikungunya have been reported from West Bengal and Orissa too. A few months ago, Italy discovered, to its alarm, that a returning resident, who picked up the infection in Kerala, set off a chain of transmission with local mosquitoes in two neighbouring villages in the north-east of the country. There are now fears that viral transmission could resume when mosquito numbers increase again in the spring of 2008. As a result, chikungunya might spread further in Italy and perhaps to other parts of Europe as well.

Chikungunya is believed to have originated in Africa where forest-dwelling mosquitoes circulate the virus among wild non-human primates. “In South Africa, chikungunya is transmitted between African Grey Vervet monkeys and also between baboons by mosquitoes belonging to the Aedes furcifer/cordellieri complex,” according to Peter Jupp, a medical entomologist formerly with the country’s National Institute for Viology (NIV) and National Institute of Communicable Diseases. “The same mosquitoes feed on man and infect him when he is present in the same areas where the monkey-mosquito cycle is occurring,” he told this correspondent in an e-mail. However, the virus was not thought to be endemic in South Africa itself, but could be entering the country from neighbouring Zimbabwe and Mozambique, he added.

The chikungunya virus was first isolated from the blood serum of a patient during a dengue-like epidemic that broke out in Tanzania in 1953. Since then, many outbreaks of the disease have been documented in Africa, South Asia and South-East Asia.

In India, the first recorded outbreak happened in Kolkata in 1963, followed by epidemics along the the east coast and elsewhere during 1964 and 1965. Nearly four lakh cases were reported in Chennai alone in 1964. Then there was an outbreak in the small town of Barsi in Maharashtra in 1973.

“After that [the Barsi outbreak], there was silence,” remarked Vidya Arankalle, senior deputy director of the NIV in Pune, in the course of a talk she gave during the recent annual meeting of the Indian Academy of Sciences in Thiruvananthapuram. In view of the long absence of chikungunya epidemics, it was postulated that the virus had disappeared from India and South-East Asia, she observed in a paper published along her colleagues in the Journal of General Virology earlier this year.

The virus then re-emerged with a bang. “The scope of the 2005-2007 outbreaks is certainly of unprecedented magnitude,” noted Ann Powers and Christopher Logue of the Division of Vector-Borne Infectious Diseases of the U.S. Centers for Disease Control and Prevention in a review paper published this year.

Using the latest tools at their disposal, including the ability to sequence and scrutinise the viral genes, scientists are trying to understand how the strain that set off the 2005-2007 outbreaks might have emerged and what makes this virus so virulent.

Based on their genetic similarities, chikungunya viral strains fall into three groups. Two of these groups are primarily Africa-based: the strains of the West African type form one cluster while those from East, Central and South Africa (ECSA) form a separate one. The third group comprises of strains found in Asia.

A team of French scientists sequenced almost the entire genome of six viral samples and partially sequenced a single gene of another 127 viral samples from the Indian Ocean island outbreaks. The study published last year by Isabelle Shuffenecker and fellow scientists at the Institut Pasteur in France in collaboration with clinicians and virologists showed that the same strain had caused those outbreaks and that it belonged to the ECSA grouping.

“Although, to our knowledge, no outbreak was reported recently in East Africa, this scenario is compatible with the human population exchanges between East Africa and Comoros [island], where the outbreak is believed to have started,” observed the scientists in their PLoS Medicine paper. But the possibility of the epidemic strain having been produced by the evolution of a hitherto animal virus could not be excluded, they added.

When NIV scientists sequenced viruses involved in outbreaks in five Indian States during 2006, they discovered that these too belonged to the ECSA group. Hitherto, the viral strains that caused previous outbreaks of chikungunya in the country had been of the Asian type. Moreover, the 99.9 per cent genome sequence similarity between the strains found in the Reunion Island in the Indian Ocean and in India “implies circulation of the same strains in both countries,” concluded the NIV scientists in their journal paper. “It also indicates a possibility of spread of the current strain from Indian Ocean islands to India, leading to an explosive epidemic of the ECSA genotype and not the Asian genotype that circulated earlier,” they added.

But there is another possible origin for the epidemic strain. In 2000, the chikungunya virus had been isolated from a mosquito found in the town of Yawat in Maharastra, although no cases were reported among humans at the time. “This strain has suddenly become very important for us,” remarked Dr. Arankalle in her talk at Thiruvananthapuram. When the genome of this virus was sequenced, it too was found to belong to the ECSA group and not the Asian variety. “That means we had the African genotype in India before ... the epidemic came in 2005,” she pointed out.

So might the Yawat strain have continued to circulate quietly in India since 2000, accumulating mutations till finally it turned into a form that spread with devastating rapidity and virulence among humans?

NIV scientists have been re-analysing their samples going back to 2001, taken from patients with dengue-like symptoms but who tested negative for dengue. They found that sporadic cases of chikungunya had indeed occurred in India between 2001 and 2004. “Right now what we are trying to do is to get [the] virus out of these cases,” said Dr. Arankalle in Thiruvananthapuram. “If we can get [the] virus from one of these cases, then we will be able to sort out as to why the Yawat virus did not produce the disease and what happened subsequently till 2005 when we had such a bad epidemic.”

However, in a brief piece published in the New England Journal of Medicine this year, Sylvain Brisse, Isabelle Iteman and Dr. Schuffenecker of the Institut Pasteur took the view that the strain that caused the outbreak in India was not the same as the one responsible for the disease on the Indian Ocean islands. Their analysis was based on comparing the genetic sequences among different strains for the viral gene that codes for one particular protein (E1). They also argued against “a direct link” between the Yawat strain and the strain implicated in the 2005-2006 Indian outbreak. But the fact that the Indian and Indian Ocean isolates shared two changes in their E1 gene sequence indicated a common ancestry for both, they stated.

Twist in the tale

There is, however, a further twist in the tale. E. Sreekumar and his team at the Rajiv Gandhi Centre for Biotechnology in Thiruvananthapuram have been examining viral samples from chikungunya cases in Kerala during 2006 and 2007. They found that the E1 gene sequence of four viral samples from Kerala this year showed an extraordinary level of resemblence to that of the Reunion Island strain. One possibility was that the virus circulating in the State had mutated, observed Dr. Sreekumar. The alternative explanation would be that a strain that originated in the Indian Ocean islands had a hand in this year’s epidemic in the State. “We need to do more analysis to answer that question,” he told The Hindu.