Kyasanur Forest Disease

Viral challenge

Print edition : March 01, 2019

Vaccine being administered to prevent Kyasanur forest disease in Shivamogga district on December 31, 2018. Photo: VAIDYA

Haemaphsalis sp.

Ixodes sp.

Ornithodorus tick.

A troop of langurs. Adult ticks are occasionally found attached to sick and dead monkeys.

The common shrew.

Rhinolophus rouxii.

A team of experts observing ticks on a rat in the Tirthahalli forest area of Shivamogga district on January 20. Photo: VAIDYA

With Kyasanur forest disease reappearing in new territories, an intensive scientific study is needed to know how the virus enters the forest ecosystem of the small mammals-tick-monkey-man cycle from the closed bat-tick-bat cycle.

KYASANUR forest disease (KFD) has broken out in new territories in Karnataka. With rapid changes taking place in the ecosystem, one should not be surprised if the disease reaches epidemic proportions. Most of the salient features in the epidemiology of KFD have already been described by Jorge Boshell-Manrique, a Colombian epidemiologist (1968). There are still some areas that need to be studied.

The first serological survey for arboviruses, conducted in 1949, gave many indications that KFD could appear in several areas with ecological conditions similar to that of Shivamogga district in Karnataka, where the disease was first reported in Kyasanur village in 1957. The reported appearance of new foci in recent years confirms this. Purely to satisfy scientific curiosity, long-term research has to be initiated in several areas to understand the natural cycle of this virus.

Natural cycle of the virus

While studying the natural cycle of the KFD virus, this writer encountered a colony of insectivorous bats, Rhinolophus rouxii, in an abandoned well in a remote village in Shivamogga district in 1969. The bats fed exclusively on insects but must have also been feeding on the ticks infesting them in their habitat. The bats were found infested with a soft tick, a new species called Ornithodoros chiropterphila. The KFD virus was isolated from several of these bats and from the ticks on them and those found on the wall of the wells. There is, thus, a closed bat-tick-bat cycle silently occurring in nature. How the virus has got out of this cycle and entered the small mammals-hard tick-monkey-man cycle is yet to be investigated fully.

In recent years, several States on the western coast of India such as Kerala, Karnataka, Goa and Maharashtra and a small pocket in Nilgiris district of Tamil Nadu have reported sporadic human cases of KFD and monkey deaths. Compared with previous epidemics of KFD during 1957-60, the finding of the virus in bats and their tick parasites should have stimulated interest among researchers, particularly since bats are known to carry many viruses (Frontline, August 4, 2017).

KFD is a zoonotic disease. The virus exists in an enzootic cycle with the involvement of several species of small mammals and passerine birds that inhabit the forests adjoining human habitations. The virus has been isolated from several species of ticks that attach themselves to small mammals. These mammalian hosts were found to circulate higher titres of the virus for various durations infecting their ixodid ectoparasites, proliferate quickly, and play an important role in the distribution of infected ticks within the range of their movement in the forests. New susceptible hosts replace the ones that are immune in quick time. Among the ticks are several species of Haemaphysalis, the chief vector of diseases of humans, and two species of Ixodes, I. petauristae and I. ceylonensis.

The most important small mammal is the common shrew, Suncus murinus, an insectivore often mistakenly classified as a rodent. It is heavily (proportionate to its size) parasitised simultaneously by Haemaphysalis (the vector of diseases in humans and monkeys) and Ixodes sp. The virus has been isolated from Ixodes and Haemaphysalis collected from the forest floor and as ectoparasites from rodents and shrews.

Tick burdens

After several years of continuous studies in the forests, it was found reasonable to conclude that small mammals, particularly the shrew, play a significant role in the transfer of infection from Haemaphysalis sp. to Ixodes sp. and vice versa. This is important in the epidemiology of the KFD virus since the population of Ixodes is higher than that of Haemaphysalis during the prolonged monsoon season, when both human cases and monkey deaths are rare. There was evidence that tick burdens were affected by extrinsic factors likely linked to local climate. Intrinsic factors were found to affect tick burdens. Larva and nymph tick burdens were positively correlated with host body size. After controlling for body size, the residual variation in tick burdens for I. petauristae larvae and nymphs was attributed to unmeasured qualities of rodent and shrew species. The role of rodents and shrews as important hosts for immature stages of ticks, especially larvae, has to be highlighted.

My studies showed that tick burdens on rodents and shrews were affected by a complex combination of local climate and host factors, making some individuals more likely to contribute to the life cycle of ticks and the enzootic transmission cycle. To better understand tick-borne diseases, one must put more emphasis on intrinsic factors since these may have a major impact on the small mammals’ contribution to enzootic transmission.

One of the hypotheses that needs to be investigated is whether ticks of the Ixodes genus are the medium of survival of the KFD virus during the monsoon season since they survive for a longer duration during heavy rains. The nymphs of H. turturis have also been found to help in the trans-monsoonal survival of the virus. Then there is the question of the soft tick, Ornithodoros, from which the KFD virus has been isolated. O. savignyi, the vector of African sleeping sickness, is known to live for more than two years as a fed adult. From the closed bat-tick-bat cycle how does the virus enter the forest ecosystem of small mammals-tick-monkey-man cycle?

From a purely academic point of view, if not epidemiological, the mechanism of survival of the virus in the ecosystem must be investigated particularly when there is no epidemic of KFD in humans or an epizootic in monkeys. Who could explain the sporadic and sudden appearance of KFD human cases or monkey deaths in different parts of India in recent years? It needed high motivation and scientific interest, as displayed by the Rockefeller Foundation, which collaborated with the Virus Research Centre (now the National Institute of Virology) in Pune from 1952 to 1970. (In 1970, the great Foundation, which had worked on Arbovirus Research in Uganda, Brazil, the West Indies and India, among other countries, pulled out of the research and closed down its research stations.)

In order to appreciate the different phases of the natural history of an infectious disease and the degrees of likelihood of its passing from a latent, slow phase to an acute stage, one needs to assess all the possible modifications of the factors involved.

The problem becomes more complex, however, with each intervening factor, be it a vector and an amplifying mechanism involving it, or a reservoir or a susceptible receptor. Indeed, when many factors are involved, the flare-up seems so improbable that often one’s first astonishment at seeing the process limited to a specific area gives way to wonder that it could happen at all.

Attempting a solution of an eco-epidemiologic riddle as complex as KFD should logically proceed by way of investigations bearing on the following:

1. The possibility of a foreign source of infection (already ruled out);

2.) The possibility of local endemic maintenance with periodic flare-up;

3.) The dynamics of the maintenance mechanism. Vectors (invertebrates) and vertebrate hosts and their interactions with the vectors and the virus;

4.) The possibility of an amplifying mechanism; and

5.) Environmental factors and their variations.

A whole set of ecological changes—including deforestation, intensified and changing agricultural practices, and invasion by alien plants—has been developing in the KFD area in close conjunction with a rise in the human population. The pace of this development has increased in the past few decades. These man-made factors appear to be favourable for the eventual enhancement of lurking enzootic processes, presumably pre-existing in the area, thus preparing the way for the flare-up. Admittedly, however, only evidence relating to the conditions as they exist today is now obtainable, and such evidence cannot be considered as definite proof of past events.

Virus persistence

The KFD virus has been detected in the complex formed by small mammals and their ticks throughout the year. We have seen it carried through three seasons in the temporary reservoir constituted by tick instars. Conditions exist, therefore, to ensure a virus maintenance mechanism. The fact that the bulk of the small-mammal population is made up of relatively inefficient porters and that, except for the squirrel, their levels of tick infestation are far below these levels for monkeys or birds, constitutes a factor favourable to virus persistence. In general, maintenance does not depend on the existence of optimal vector-porter conditions for virus transmission and multiplication since these would lead to exhaustion of the enzootic fuel and to an end of the process.

The data on both tick infestation levels and population dynamics of rodents and shrews point to virus maintenance as a definite possibility. Confirming evidence is, however, still lacking.

So far, the KFD virus has not been isolated outside the infected area from either porter or vector. An attempt to achieve such an isolation in areas where slow-moving zoonoses prevail would defy most operational capabilities. The KFD virus isolations made at Sagar (Shivamogga district) may well have been the result of feedback by an amplifying mechanism into the slow-tempo cycle, which thus became detectable. As evidence stands now, it is not possible to dissociate the infection of small mammals from that of simians or even squirrels; neither is it possible to affirm that the infection originated in small mammals. The starting point of the 1957 flare-up is thus still in question.

Only long-range, costly and painstaking studies in zones devoid of acute simian involvement could bring final proof of an occult process lurking among small mammals and their Ixodid ectoparasites.

The maintenance of the KFD virus in adults of certain tick species has been demonstrated 14 months after the infection of the larvae; furthermore, adult ticks are occasionally found attached to sick and dead monkeys. These findings, given the constant possibility of transportation of nymphs by birds, cattle and other animals, suggest a mechanism not only of virus maintenance but also of virus propagation. While flare-ups may yet occur in the few spots bypassed so far, it is unlikely that their frequency will be such as to increase substantially the probability rate of human attack. All this is as far as the so-called present infected area is concerned.

In short, KFD flare-ups in many areas are a reality, and their actual occurrence is presumably dependent on attainment of the necessary quantitative thresholds. What are these threshold levels? In-depth, long-term investigations alone, and not casual visits, will throw some light on why KFD is occurring sporadically in different places.

P.K. Rajagopalan is a former Director of the Vector Control Research Centre in Puducherry, an institute of the Indian Council of Medical Research.

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