Vector-borne disease research in India

Ailing research

PAYYALORE KRISHNAIER RAJAGOPALAN

Vector-borne disease research in India has remained stagnant for decades owing to administrative apathy and lack of proper policies. By PAYYALORE KRISHNAIER RAJAGOPALAN

     THERE are many vector-borne diseases (VBD) prevalent in India apart from malaria and filariasis, such as Kyasanur forest disease, Japanese encephalitis, scrub typhus, dengue and chikungunya. The control of all of them depends on an understanding of the natural cycles and epidemiology of their vectors. Malaria, for example, is ideal for explaining VBDs because a lot of fieldwork was done on it by scientists all over the world, particularly British scientists in pre-Independence India. Their endeavours had led to a clear understanding of the ecology and behaviour of the vectors involved, which helped in devising appropriate control measures.

       A review of the research work that led to malaria control demonstrates how science had progressed over the period. Some of the important landmarks in the control of the disease were achieved by biologists and naturalists with a deep understanding of the environment. The first and foremost among them was Sir Ronald Ross, who in 1897 discovered that mosquitoes transmitted malaria. The relationship between the mosquito and the malarial parasite and their adaptation to their environmental ecology had been studied by many. These studies revealed that the transmission was very significantly influenced by many factors, including human activity.

The relationships between vector control and transmission among the mosquito vector, the parasite, the environment, and the behaviour of human carriers have been extensively studied by many. The researches also laid emphasis on the environment and how it contributed to malaria. The environmental studies covered local vectors, ecology, demography, agriculture, and so on. They found that local environmental conditions contributed to the disease, especially in specified zones. The link between parasite transmission and vector control predicated a need to understand other factors that led to malarial transmission. Dr Paul F. Russell was one of the stalwarts who studied malarial transmission. Nicolaas Swellengrebel coined the term “species sanitation” to link the carrier anophelines species with specific habitats, which explained the connection between ecology and malaria. It was found that factors such as availability of local vectors, ecology, demography, race and culture played a significant role in the transmission of the disease.

According to Ross, what was required was not the complete elimination of mosquitoes but a reduction in their numbers to below a certain level, now known as “critical density”. Ross also identified the human factor in the transmission. Malcom Watson in Malaysia and Russell and T. Ramachandra Rao in India demonstrated for the first time the validity of the concept of “critical density” of the vector. In pre-independent India, most of the notable contributions were made by scientists such as Muirhead Thomson in Assam, R. Senior-White and colleagues in Orissa (now Odisha), M.O.T. Iyengar and Sen in Bengal, Russell and Ramachandra Rao in south India, D.K. Viswanathan and Ramachandra Rao in the old Bombay State, and B.A. Rao in Mysore State. They contributed a lot to our understanding of the bionomics and ecology of such vectors as A. culicifacies, A. stephensi, A. minimus, A. fluviatilis, A. philippinensis, and A. sundaicus. In India, the period between 1930 and 1945 could be regarded as the golden era of studies on the bionomics and ecology of malaria vectors. The work by the Malaria Institute of India under the leadership of Sir Gordon Covell needs to be remembered in this respect.

On vector control, pioneering work was done in India by Russell and Ramachandra Rao in the late 1930s; they used pyrethrum as a space spray against anophelines in the malaria-affected areas of Pattukottai (Thanjavur district, Tamil Nadu) where irrigation practices were defective. It was used inside houses against the adult A. culicifacies. Spraying of pyrethrum extracts in the form of mist inside human dwellings during daytime killed the adult mosquitoes resting inside.

They extended their work to North Kanara district of the old Bombay State, which was one of the most malaria-prone areas in the country. Sprays were ineffective here because the vector, A. fluviatilis, rested outdoors. Then DDT appeared on the scene and revolutionised the entire project of malaria control. It was sprayed on the walls and ceilings of human dwellings because the vector mosquito rested there after taking an infected blood meal. This method was successfully used to protect civilian populations by Viswanathan and Ramachandra Rao in North Kanara in 1945 and by Senior-White in Orissa. Almost simultaneously, B.A. Rao and others tested it successfully in other parts of the country. In 1946, Viswanathan and Ramachandra Rao launched one of the largest malaria control projects in the rural tropics—seeking to protect over one million people, in the districts of North Kanara and Dharwar in Bombay State—and it proved to be a remarkable success. Mahatma Gandhi himself praised their efforts.

During the initial years, the control programme was a tremendous success, and was hailed all over the world. All other methods of mosquito larval control, such as the use of the Gambusia fish, larvicides like Paris green, and environmental control, were given up as they did not seem necessary. But in the mid-1960s, malaria came back with a bang. Owing to the euphoria created by the success of vector control in the early 1960s, malaria research, which should have continued, had practically come to a standstill. The Indian Journal of Malariology, which had apparently lost its relevance, had stopped publication.

A.P. Ray, the architect of India’s successful malaria control programme, could be compared to Fred Soper, who organised a successful malaria control programme in the Panama Canal Zone in the pre-DDT era. But Ray failed us in one important aspect. He depended too much on the efficacy of DDT and could not foresee vector adaptation to chemical pressure. Insect resistance to chemicals was not well known at the time. The initial success of DDT made him think that there would be no further need for entomologists in mosquito control work. Many were diverted to family planning operations or had their services terminated. Only the junior supporting field staff were retained to continue with the DDT spraying programme. For this policy choice, India paid a heavy price. There were no trained scientists left to quantify the extent of damage done by DDT-resistant vectors and put in place a policy to minimise the damage.

As Ray himself pointed out, all major malaria vectors in the country became resistant to the two commonly used and comparatively inexpensive insecticides, namely DDT and benzene hexachloride (BHC). When the incidence of the disease was at its lowest between 1964 and 1966 there was slackness in the allocation of funds and procurement of insecticides, leading to inadequate and untimely spraying in many parts of the country. India, like many other developing countries, almost always followed the advice of the World Health Organisation. The WHO recommended organochlorine insecticides (DDT, BHC, etc.) first, then organophosphorous insecticides (such as malathion), then carbamates, followed by synthetic derivatives, and so on. Newer methods of application were then suggested with the existing insecticides. Use of insecticide-impregnated nets (IIN) or variations of it were recommended by the WHO. These were supplied by multinational companies, which helped them make huge profits. They also financed research projects in India through the WHO. Many foreign universities sought collaboration with Indian institutions. There were also field trials with different kinds of prophylactic drugs. Present-day malarial mosquito research has been going on for the last two or three decades, with scarcely anything coming out of it.

Vaccine for malaria

How do we vaccinate our rural populations, about 300 million of whom live in areas where they are exposed to infection? How long will it take for the best of vaccines to provide even partial immunity to our vulnerable population? Why do we find mixed infections with two or three species of parasites in the blood of the same individual? Immunity from the malarial parasite is incomplete, so the vaccine has to be very good. Even the most severe case of naturally acquired malaria does not protect most people from a second round of infection.

In 1980, Dr Adetokunbo O. Lucas, Director of the WHO Tropical Diseases Programme, in an informal discussion with the WHO Expert Committee on Vector Biology and Control in Geneva, predicted that a “malaria vaccine was just round the corner, and the committee will be able to concentrate on the problems of the other vector-borne diseases within a foreseeable future or the committee can wind up their effort and simply go home.” Dr Lucas was well aware how much money was being invested on this research worldwide, especially in the United States, which had an abundance of expertise and resources. More than 30 years later, we are no nearer a breakthrough, despite many of the world’s leading institutions working on a viable vaccine. It is possible that the microbiologists and immunologists will ultimately be able to produce such a vaccine but we may have to wait for many more years. Undoubtedly, research on this subject has to be greatly accelerated and financially supported.

There is certainly a lack of trained manpower to do malaria research. The work culture almost everywhere in India, including in research institutions specially created for malaria research, has lost its momentum owing to neglect, ignorance or poor planning. Medical entomology in early days was pioneered by trained people who had an instinctive knowledge about developing tools to prevent the spread of the disease. Their expertise was critical in guiding vector control efforts. The scientists toiled in the field, in rain and slush, to obtain essential information on mosquito behaviour, which anti-mosquito tools to use, and so on. Among the Indian entomologists, the late Ramachandra Rao wrote an excellent book, Anophelines of

India.

There is a lack of proper measures to control many of our endemic diseases because of the ineffective application of known procedures and an unwillingness to address the real causes of failure. Our control efforts need more operational research. Prompt diagnosis, immediate hospitalisation, and supportive treatment are necessary. The WHO has to take the major blame for the failure. There was a Vector Biology and Control (VBC) division in the WHO which had done excellent work in the past. This was renamed the Division of Molecular Entomology, presumably with vaccine development in mind. Unfortunately, the emphasis shifted from the field to the laboratory. Universities in India which had departments of zoology and entomology now have departments of life sciences and biotechnology instead. In many medical research institutions, the entomology division was progressively downgraded.

The National Vector Borne Disease Control Programme in India has been facing a staff crunch— many positions of entomologists remain vacant. In 1985, one research institute started a two-year master’s course in Medical Entomology, initially supported by the WHO. The course produced many well-trained entomologists. But it was discontinued in the late 1990s because the graduates could not find jobs in India. Another master’s course, in Public Health Entomology, was started a few years ago in the same institute. This course may also be abandoned soon as the degree has not yet been recognised by

the employing institutions.

The epidemiology of any vector-borne disease is quite complex. The parasite or pathogen (be it a virus, a bacteria, a protozoan or a helminth), the mosquito, the human victim and the environment are all intimately interwoven. In the case of malaria, four (now five) species of human plasmodia with differing biology are involved, and so are numerous vector anophelines, each with its own peculiar bionomics and ecology. Human susceptibility to the disease also varies with the environment and society. And finally, the environment has an infinite variety of features. Most of the arbovirus diseases are of zoonotic origin. The latter do not feature in today’s research priorities in India. In the case of two common diseases, dengue and chikungunya, though there is evidence of a zoonotic cycle, no meaningful work has been done. The Kyasanur forest disease, transmitted by ticks, and scrub typhus, transmitted by mites, are re-emerging in India. Birds and animals, both small and large and wild and domestic, are also involved in the transmission. The forest is one environment with many vectors.

We can only aim at controlling VBDs as it is not possible to eradicate them. The vector population should be kept below the critical level. To do this, we must know all aspects of the vector populations and their build-up, their drivers, the environment and human ecology. The role of medical/field entomologists is therefore crucial in the control of VBDs.

Dr Payyalore Krishnaier Rajagopalan is a former Director of the Vector Control Research Centre in Puducherry.

(Published in Businessworld.in)