Battle against mosquito

Payyalore Krishnaier Rajagopalan spent all his professional life fighting the mosquito menace in India and striving towards eliminating vector-borne diseases.

Children afflicted with Japanese encephalitis in a ward of the Malkangiri district hospital in Odisha on October 8, 2016.

MOSQUITOES have a prominent place in human history, and the deadly diseases, such as malaria and Japanese encephalitis (JE), they visit on humans have been variously chronicled. We, in India, thought that we had conquered malaria in the 1960s, but the cheeky mosquito continues to dodge the best efforts of the human brain. In this ongoing battle against the mosquito, the insect is currently winning. This article narrates the details of the indefatigable battle the biologist Payyalore Krishnaier Rajagopalan waged against mosquitoes.

Rajagopalan was born as the second son to P.R. Krishnaier and T.A. Gowri in Mukteswar, a hill station in the Kumaon Hills (now in Uttarakhand), on October 27, 1930. Young Rajagopalan grew up in present-day Palakkad under the care of his maternal grandfather. After secondary schooling, Rajagopalan moved to Varanasi in 1945 to study at the Banaras Hindu University.

He completed an MSc in zoology with entomology as specialisation in 1951. In 1953, he joined the Rockefeller Foundation’s Virus Research Centre (or VRC, which was renamed the National Institute of Virology in 1978), Pune, as a research assistant. He rose through the ranks to become Assistant Director in early 1970. He was appointed Deputy Director of the Research Unit on the Genetic Control of Mosquitoes (RUGCM), New Delhi, which was an initiative of the World Health Organisation (WHO)/Indian Council of Medical Research (ICMR). He was at this post until 1975. He was then appointed Director of the Vector Control Research Centre (VCRC), which was newly started under the aegis of the ICMR. For 15 years, Rajagopalan led the VCRC on a trail-blazing path in the battle against mosquitoes. He retired in 1990 and is based in Chennai.

While Rajagopalan was at the VRC, the Government of India deputed him for advanced training in medical epidemiology to the University of California Berkeley where he pursued a master’s in public health. While at the university’s Department of Epidemiology in the School of Public Health, Rajagopalan was trained by William C. Reeves, who considered it critical for him to get training on malaria from Lewis W. Hackett of the International Research Division of the Rockefeller Foundation and on zoonotic diseases from Karl F. Meyer of the Hooper Foundation for Medical Research because he came from a developing nation. Reeves also arranged for Rajagopalan to gain experience at his encephalitis field laboratory in Bakersfield, California. Rajagopalan cherishes what he learned while in the United States about the value of hard work, honesty and research ethics.

In 1965, he completed his PhD at the University of Poona (now the Savitribai Phule Pune University).

Rajagopalan was fortunate to come under the tutelage of the pioneering Indian medical entomologist Thammaji Ramachandra Rao (T.R. Rao), who trained him in sampling mosquito ecology and generously enabled his scientific encounters with the mosquito and its biology in the 1950s.

At the VRC, Rajagopalan was charged with the task of dealing with the then newly recognised viral disease Kyasanur Forest disease (KFD) in Hassan district of Mysore State (now Karnataka). Whether the virus was transmitted by migratory birds from Siberia was a daunting question that had to be answered. Over the course of a two-year investigation, Rajagopalan examined about 8,000 birds and extracted some 10,000 ectoparasitic ticks but, curiously, found no exotic ticks. Tests of the blood sera from the birds at the VRC disclosed a cross reaction to the Russian Spring-Summer encephalitis complex, which indicated that KFD was indigenous. Salim Ali of the Bombay Natural history Society trained Rajagopalan in the handling of birds and understanding migratory ecology.

Arboviruses & anthropods

The distinct absence of yellow fever in India was a key factor behind the establishment of the VRC and the evolution of a committed interest in medical entomology and acarology in the country in the late 1950s. Rajagopalan was one of the beneficiaries of this interest. With JE being recognised in 1954 and KFD being reported in 1957, interest in arboviruses and their transmitting arthropods grew significantly in India. Rajagopalan studied the ecology of several medically relevant arthropods of Devimane Ghat, a virgin tropical evergreen forest in what is now Uttara Kannada district of Karnataka. This study included extensive sampling of arthropods and collection of blood samples from a large number of humans and other mammals for serology and characterisation of possible viruses.

Devimane Ghat was Rajagopalan’s first field site, where he learnt about the spatial distribution of mosquitoes in a tropical forest. The theory uppermost in Rajagopalan’s mind was that these arboviruses had zoonotic origins. He and his team had an unequivocal demonstration of this while working on KFD. The construction of a dam across the Sharavathi river in 1964 inundated an extensive natural forest area and displaced the wild animals that lived there. This forced the ectoparasitic ticks present on the animals to move into human suburbia and eventually live by parasitising livestock. Rajagopalan’s studies at the Devimane Ghat site enabled him to clarify vital but unknown aspects of the zoonotic cycles of various viruses.

Rajagopalan was posted to Vellore, Tamil Nadu, in the mid 1950s when there was a breakout of JE. He and his team sampled thousands of culicine mosquitoes ( Culex vishnui group) and were able to isolate the JE virus. The work on JE was extended to Akividu, Andhra Pradesh, to explore the role of migrant birds in introducing the JE virus to an area since pelicans and similar birds nested in the Akividu lake. He realised that operational research methods were sorely needed to manage the populations of medically relevant arthropod vectors. He was interested in exploring what the most practical and viable methods to save human lives would be and how one could predict an epidemic.

While at the RUGCM, he studied the ecology of C. quinquefasciatus , the mosquito that transmits filarial nematodes. The RUGCM’s mandate was to manage malarial and filarial vectors through genetic manipulation. The RUGCM folded up in 1975 because of a political controversy.

The sterile-insect technique trialled in the Midwestern U.S. to manage populations of screw-worm flies was considered a turning point in the management of nuisance insects. The females mated once in their lifetime, which is also the case with mosquitoes. Because of a distinct size difference between the pupae of male and female screw worms, after successfully mass rearing them, American scientists were easily able to separate the male pupae and sterilise them with radioactive exposures, and release them into natural populations. This practice reduced the screw worms that affected American cattle.

A few foreign and Indian medical entomologists were keen on trialling sterile-insect technique to regulate mosquito populations. But it was not possible to segregate the sexes in mosquito pupae. A 2 to 5 per cent contamination, which is a large number considering the size of mosquito populations in India, always prevailed during the segregation of male pupae from females. Moreover, the sterilised and genetically manipulated male mosquitoes were not as competitive as the males in the wild, and therefore the results were disappointing.

Rajagopalan’s leadership qualities came to the fore after he took over the reins of the VCRC in 1977 as its first Director. The then Director General of the ICMR, Colathur Gopalan, saw the need to establish a centre to manage the exploding populations of mosquitoes in southern India, and the VCRC was born in Puduchery in 1975. Over the next few years, it grew into a premier organisation offering cutting-edge knowledge on the ecological management of different species of mosquitoes.

Today, it has grown into a centre of excellence for research and training in vector-borne diseases and control and a WHO collaborating Centre for Research and Training in Lymphatic Filariasis and Integrated Methods of Vector Control because of Rajagopalan’s vision and unstinting efforts. It is due to him that a two-year-long master’s programme in medical entomology, unique in India, commenced at the VCRC in 1986. Close to 20 students got their PhDs with Rajagopalan as their principal supervisor in various sub-disciplines at the VCRC.

A key strategy Rajagopalan designed and launched was locality-specific management, which was based on a comprehensive understanding of mosquito biology and the manner in which the insect transmits protozoan or nematode parasites. The Filariasis Control Demonstration Project, which used large-scale, integrated vector management (IVM) tactics, was launched in 1980. It reduced filarial parasite ( Wuchereria bancrofti ) infections in Puduchery. The IVM tactic entailed the reduction of the population density of C. quinquefasciatus , the agent that transmits W. bancrofti .

Rajagopalan established a research project in Cherthala (Kerala) to manage C. quinquefasciatus , which transmits the nematode Brugia malayi . The Cherthala project involved the physical and mechanical removal of the water plants that served as breeding sites for C. quinquefasciatus . Another VCRC project aimed at mosquito management at Rameswaram Island by targeting the unusual breeding sites of the Anopheles culicifacies , the local malarial mosquito. The issue was complicated by periodical movements of local human residents, mostly fisherfolk, who passively transmitted the parasite to nearby islands and mainland India. The malarial parasite confined to this island was resistant to common anti-malarial drugs.

Rajagopalan investigated the breakouts of JE in Tirunelveli, Tamil Nadu (1978), and in Burdwan and Bankura, West Bengal (1976). He demonstrated that JE was seasonal and that its epidemiology varied subtly in different regions. C. tritaeniorhynchus breeds profusely in rain- and floodwater pools and feeds on livestock. Rajagopalan was of the opinion that forecasting an epidemic and initiating proactive measures of vector control was more significant than implementing management strategies later. He vehemently argued that this strategy necessitated long-term studies on vector populations in JE-prone areas so that an epidemic breakout could be prevented. Even a 50 per cent reduction in the vector population, Rajagopalan argued, would prevent an outbreak.

Since C. tritaeniorhynchus was zoophilic, only the odd mosquito would bite humans. His argument that the human was an incidental link in the endemic infective cycle between C. tritaeniorhynchus and wild birds deserves a thorough investigation today. Under certain specific circumstances, larval control measures could be practical and economically justifiable, but Rajagopalan was of the strong opinion that they would not work in the context of JE virus transmission as he argued in the article “Combating a killer” ( Frontline , November 30, 2012).

To investigate tribal malaria, he opened a field station in Jeypore, Koraput district, Odisha, where he encountered difficulties with the terrain and the hostility of the local people. Malaria due to Plasmodium falciparum and P. vivax had been persistent in this region for several years. Rajagopalan’s wise decision to appoint a woman doctor to deal with the health needs of the tribal women in particular and to have the VCRC distribute medication free of cost enabled it to gain the trust of people in Jeypore. The VCRC team found that cases of P. malariae and P. ovale also occurred there. The Jeypore field station was a jewel in the crown of the VCRC because it demonstrated how quality work could be achieved in adverse, and even dangerous, conditions. The VCRC was able to carry out long-term ecological studies on mosquitoes.

In addition to the battlefronts referred to above, Rajagopalan made efforts to address key issues relating to a few other vector-borne diseases, such as lymphatic filariasis and dengue. During his time at the VCRC, he worked closely with various national and international agencies, such as the WHO, identifying evidence-based solutions for operational challenges faced in various vector-management programmes. The Royal Society of Tropical Medicine & Hygiene, London, recognised him as a Fellow in 1990. The Government of India conferred the Padma Shri on him in 1990.

All through his professional life, Rajagopalan fought the mighty mosquito and strove towards achieving the goal of better health for his fellow citizens. He may not have been 100 per cent successful in his efforts to keep mosquito populations within reasonable threshold levels, but his efforts were always genuine.

Anantanarayanan Ramanis a senior academic engaged with the ecology of insects in agricultural contexts. He currently teaches at Charles Sturt University, Orange, NSW, Australia.