Chandipura virus: an emerging human pathogen?

In this issue of The Lancet, B Rao and colleagues describe an outbreak of acute encephalitis in north Andhra Pradesh and central-eastern Maharashtra, in southern India. The epidemic started at the beginning of the monsoon season in June, 2003, and lasted 3–4 months. In the state of Andhra Pradesh, 329 children aged between 9 months and 14 years developed encephalitis, and 183 died. The usual suspect would have been Japanese encephalitis virus. However, this virus normally emerges late in the monsoon season, and the disease in the Andhra Pradesh cases progressed faster than normal from an influenza-like illness to coma and death. The patients often complained of abdominal pains and vomiting, symptoms seldom associated with infection with Japanese encephalitis virus. Indian virologists turned their attention to other viral suspects, and were able to identify Chandipura virus as the culprit.

Chandipura virus is a member of the Vesiculovirus genus of the family Rhabdoviridae. It was first isolated in 1965, from the blood of two adults with a febrile illness in a village in Nagpur County, Maharashtra State, India.¹ The only other instance when the virus was isolated in human beings was in 1980, in Madhya Pradesh, India, from a patient with acute encephalitis.² The likely vector of Chandipura virus is the female phlebotomine sandfly.³ During the 2003 outbreak, Chandipura virus RNA was detected by PCR in sandflies collected around the house of a patient with encephalitis.

Since 1965, the virus has been reported in three adjoining states in central India: Madhya Pradesh, Maharashtra, and Andhra Pradesh. The virus has probably been endemic in this region for decades, and might have been responsible for several earlier outbreaks of encephalitis that have been recorded in India since 1954. However, the geographical distribution of the virus might extend well beyond India; it has also been detected in sandflies in Senegal and Nigeria.4, 5 Do not feel too bad if you have never heard of Chandipura virus before. Since the discovery of the virus in 1965, fewer than two articles a year have been published about it. In the year after the outbreak of severe acute respiratory syndrome (SARS) in 2003, more than 1800 articles were published on the SARS coronavirus. I doubt if the Chandipura virus outbreak in central India will be followed by a similar flurry of research activity. In the zoonotic animal virus farm, all viruses are equal, but some viruses are more equal than others. But, part of the explanation for the difference in research interests might be owing to the fact that Koch's postulates were fulfilled for the causal role of a novel coronavirus in the SARS epidemic, but not yet for the association of Chandipura virus with the outbreak of encephalitis in 2003.

The story of the first discovery of the Chandipura virus and its potential role in the 2003 outbreak can not be told without mentioning the National Institute of Virology (NIV) in Pune, India. This institute was established in 1952, under the auspices of the Rockefeller Foundation and the Indian Council of Medical Research, to investigate arthropod-borne viruses. The NIV is currently a WHO Collaborating Centre for arboviruses. Only when regional surveillance networks are closely cooperating with regional reference diagnostic laboratories can they function as effective early-warning beacons for emerging infections. The US Centers for Disease Control and Prevention cannot, and should not, function as the ultimate global reference laboratory. The threshold for sending samples to a small regional laboratory is lower than that for sending it to a far away and often culturally incongruent mammoth laboratory. Strengthening the regional diagnostic laboratory facilities in developing countries is an important global-health priority, and will result in a surveillance net with smaller meshes.

A lot has already been achieved, and the diagnosis of the current outbreak of viral encephalitis is a good example of a sentinel system that worked. However, much more remains to be done: in the infectious disease sphere, there are (and I paraphrase the US Secretary of Defense Donald Rumsfeld slightly out of context here) a lot of “known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns—the ones we don't know we don't know.” The 2003 encephalitis outbreak in India taught us that the previously unknown Chandipura virus joins the seemingly ever-growing list of the known important human pathogens. I bet there are still a lot of unknown unknown infectious diseases awaiting us.