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Nailing the vector

Print edition : Jan 03, 2003 T+T-

Mosquito: A Natural History of Our Most Persistent and Deadliest Foe by Andrew Spielman and Michael d'Antonio, Faber & Faber, 2001; Paperback, pages 247, 7.99.

TO people living in areas prone to malaria, the whine of a mosquito could be the music of death. Every 20 seconds, someone somewhere dies of malaria, which is caused by a small protozoan parasite transmitted by the female mosquito, which can introduce 30 to 40 parasites into the human bloodstream in a single bite. Malaria is the third deadliest disease, after dysentery and tuberculosis. It is estimated that every year, between 300 and 500 million persons are infected by malaria, of which over a million people perish, most of them children under five years of age in Africa and Asia. Malaria is endemic in about 100 countries, affecting 40 per cent of the world's population.

Professor Andrew Spielman of Harvard University and journalist Michael d'Antonio point out in their scholarly and authoritative book Mosquito: "Mosquitoes have felled great leaders, decimated armies, and decided the fates of nations." Ancient Rome was the malarial capital of Europe. Romans believed that malaria was caused by bad air (mal aria in Italian). For a long time, it remained a mystery, and was associated with "emanations" from the earth. In Rome, it killed both peasants and Popes. Even Alexander the Great was no match to the malarial mosquito, whose bite probably killed him in 323 B.C.

In the first part of the book, Spielman and d'Antonio offer an insight into the world of the mosquito, which they refer to as the "angel of death". The second part deals with other mosquito-borne diseases such as filariasis, yellow fever and dengue. In the final section, the book outlines the history of man's struggle to live with the mosquito, assesses the progress that has been made in combating many of the mosquito-borne diseases, and draws attention to the fact that the mosquito menace continues despite advances in modern technology.

Only mosquitoes of the genus Anopheles, of which there are 60 species, are capable of transmitting malaria to human beings. Not all mosquitoes are bloodsuckers. Of the 2,500 species of mosquitoes known to science, only a minority feeds on human blood. The female mosquito needs blood in order to fuel the production of eggs.

Mosquitoes differ in their idiosyncrasies and feed on blood at different times of the day. Aedes aegypti, which transmits dengue and yellow fever, prefers to bite people on their ankle or calf. This is why many secretaries in India are seen often jiggling their legs up and down almost continuously to ward off this mosquito. The authors refer to this as the "Babu Bounce". Culex pipiens, the vector of the West Nile virus, feeds after dark. Anopheles mosquitoes are active mainly after dusk and just before dawn. Dr. Patrick Manson, the Father of Tropical Medicine, had established in 1875 the link between filariasis or elephantiasis and the mosquito (Culex pipiens) when he was in Taiwan. But he erred in presuming that the parasite was transmitted through drinking water, a mistake that he repeated in 1894 with regard to the mode of transmission of the malarial parasite. It was the Italian Amico Bignami who correctly suggested that it was the mosquito that transmitted the parasite by way of its bite. But Bignami was not the first person to observe that a blood-feeding creature could acquire and transmit a pathogen via its bite. The honour for the discovery must go to American Theobold Smith who, in 1893, demonstrated such a connection between a tick and cattle in the American west.

Spielman and d'Antonio credit the French army doctor Charles Laveran with the discovery of the malarial parasites in the blood of an infected person in 1880, for which he received the Nobel Prize. In 1886, Camillo Golgi, having identified the human malarial parasites Plasmodium vivax and Plasmodium malariae, recognised Plasmodium falciparum as the most lethal. But it was Dr. Ronald Ross, a British doctor, who demonstrated how the malarial parasite entered the human blood stream. Ross, who was born in 1857 in the foothills of the Himalayas, was educated in England. He became a member of the Royal College of Surgeons at the age of 27 and was posted in Bangalore by the Indian Medical Service. In 1894, on his return to England, Ross met Manson who encouraged him to explore the link between mosquito and malaria. On August 20, 1897, while working in Secunderabad, Ross made the critical observation that proved that malaria was indeed transmitted by the mosquito, for which he received the Nobel Prize in 1902. Ross discovered some "peculiar pigmented cells" or oocytes lodged in the stomach wall of an Anopheles (or `dappled-winged') mosquito. The oocytes were spotted after the mosquito bit a patient called Hussein Khan who had agreed to undergo the experiment; he received an anna for every bite of the mosquito.

The British Army in India was no match for the protozoan parasite; about 40 per cent of the 178,000-strong army was incapacitated with malarial fever in 1897, the year Ross identified the Anopheles mosquito as the intermediary or vector that transmitted the disease. About that time, in Panama, both malaria and yellow fever claimed the lives of two-thirds of the European workers who were engaged in the construction of the Panama Canal.

In 1898, Ross moved to Calcutta (now Kolkata) and established the cycle of avian malaria, but the credit for working out the complete life cycle of the human malarial parasite must go to the Italian team led by Giovanni Battista Grassi. Hundred and five years after Ross established the link between mosquito and malaria conclusively, the complete genome sequences of the protozoan parasite Plasmodium falciparum appeared in the issue of Nature dated October 3, 2002, while those of the mosquito vector Anopheles gambiae were published in Science on October 4. In the words of Professor P. Balaram, Editor, Current Science, the discovery of the genome sequences "marks a milestone in the long struggle against malaria".

Today, we not only know that about 60 per cent of the 5,268 genes that have been identified in Plasmodium falciparum are new to science, but that genetically Plasmodium appears to be closer to plants than to animals. Elimination of malaria will depend on the eradication of the malarial parasite or the mosquito that transmits it. Scientists fall into two camps depending on whether they believe that the key is to eradicate the mosquito or treat the sick with anti-malarial drugs. Only three out of the 1,223 new drugs that were registered between 1975 and 1996 proved to be anti-malarial. Therefore the struggle is in no way over.

One of the most aggressive and successful anti-malaria campaigns was carried out in 1900 in the United States by entomologist John B. Smith, who pioneered methods that were copied by many people. Smith was more interested in controlling mosquitoes than in their extermination. He identified the breeding areas of mosquitoes and drained them, filled them with sand pulled from river bottoms, and even poured oil onto water bodies where mosquito larvae bred. The public and the press ridiculed his efforts but they led to a crash in the population of "the New Jersey mosquito", Ochlerotatus sollicitans. Similar tough measures that were adopted in Cuba by U.S. Army Major William Crawford Gorgas eliminated yellow fever from Havana. Later, Gorgas adopted the same anti-vector measures and eliminated yellow fever from the Canal Zone in Panama by 1906. These early efforts proved that a limited area could be rendered free of mosquito-borne infection.

ONE man who campaigned vigorously for the worldwide eradication of the mosquito was an unusual American named Dr. Fred Soper, who was born in Kansas in 1893 and was educated at Johns Hopkins School of Public Health. He was a man of legendary energy, and was endowed with great common sense. In 1930, when thousands of larvae of the malarial mosquito Anopheles gambiae were discovered along a river in Brazil, thousands of miles from their homeland in Africa, Soper recommended the opening of the dykes damming the tidal flats because salt water destroys the breeding areas. But the government refused, and malaria began to spread, infecting 100,000 people and killing 20,000 in 1938. Brazilian President Getulio Vargas enlisted the services of Dr. Soper to eradicate the mosquito. Dr. Soper and his team of 40,000 workers fumigated houses and buildings with a natural pesticide pyrethrum, derived from the dried flowers of chrysanthemum, and sprayed Paris Green (a mixture of diesel oil and copper acetoarsenite) on pools of water. In just 22 months, he eradicated the mosquito from an area of about 18,000 square miles (46,900 square kilometres).

Dr. Soper's success was considered a great public health achievement in Brazil, and he was rewarded with medals and citations. This was before DDT (dichloro-diphenyl-trichloroethane) was used in anti-malaria programmes. In the late 1930s, the Swiss company J.R. Geigy manufactured DDT. It was found to be the most effective insecticide against malaria and was used extensively during the Second World War. Dr. Soper used it effectively to control the malarial mosquito Anopheles labranchiae in Sardinia. His approach was described as the "zero tolerance" approach to the mosquito. Malcolm Gladwell, in his article "In praise of DDT" (The New Yorker, 2001), referred to him as "the General Patton of entomology". Buoyed with success, Dr. Soper believed that it would be possible to eradicate the mosquito from the entire world.

The use of DDT helped reduce cases of malaria in many countries, including India and Sri Lanka. In India, DDT was sprayed widely even from elephant back. The low country dry zone in Sri Lanka was colonised using DDT manually. Agriculture was made possible largely through the control of Anopheles culicifaces, which had been crippling Sri Lanka's efforts to achieve economic self-sufficiency. In 1935 alone, some 20,000 people in Sri Lanka died of malaria. DDT was used widely as it was not only potent but also relatively inexpensive. But the initial success proved illusory, for mosquitoes began to evolve strains that were immune to DDT.

Much to Dr. Soper's dismay, public opinion began to turn against the use of DDT with the publication of Silent Spring by Rachel Carson in 1962. Silent Spring highlighted the plight of the environment under the impact of pesticides, and questioned the widespread assertion that DDT was safe. In aquatic environments, even tiny amounts of chemical pesticides are picked up by the smallest organisms, concentrated, and then passed along food chains to the larger predators through a process known as bio-amplification or food-chain concentration. It was from Rachel Carson that the public learned that DDT could seep into mother's milk and accumulate in the bodies of their babies. The silent protest led to the growth of environmental activism. But as Malcolm Gladwell points out, nowhere in the book does Rachel Carson credit the efforts of malariologists in saving almost 10 million people through the use of DDT.

In 1972, the U.S. declared the use of DDT illegal and listed it as one of the `Dirty Dozen' Persistent Organic Pesticides (POPs). Spielman and d'Antonio believe that a worldwide ban on DDT would be a mistake, for if properly used, DDT could provide great relief to the poor in Third World countries. Of all the chemicals currently available to kill mosquitoes, DDT remains the ideal insecticide of first use. "This," as the authors argue, "is because the resistance that mosquitoes develop after being exposed to DDT does little to protect them against the other, more expensive insecticides that wait on the sidelines."

In December 2000, DDT was de-proscribed so that it could be manufactured in China and India for use in anti-malaria programmes. Dr. Soper must surely be turning in his grave, for he died in 1975. Despite the fact that countries such as Taiwan and Jamaica have eradicated malaria, it is unlikely that the disease can be eliminated from the entire world in the near future. The emphasis is now on attacking the parasite with drugs. Quinine was developed from the bark of the cinchona tree, known to the Indians in South America as `quina-quina'. In Peru it grows at altitudes above 1,500 metres, where Anopheles mosquitoes do not survive. The natives use the bark to cure fever and chills. Malaria was unknown in the New World until it was introduced by the Spanish and Portuguese armies in the 16th century.

According to Pedro Cintas, the Swedish Botanist Carolus Linnaeus, who first devised the binomial system for naming plants and animals, named the tree after the Countess of Cinchon, the wife of the Viceroy of Peru, who was said to have been cured of malaria by taking an extract of the bark. But it was the Jesuit priest Calancha who learnt the bark's therapeutic value against fever and introduced it to Europe in 1633 as an antidote to malaria. Hence it is referred to as "Jesuit's bark". As Sandra Knapp points out, "malaria is an Old World disease that was initially cured by a New World plant". The alkaloid quinine was the first drug to be used widely in the control of the malarial parasite. However, with the development of synthetic drugs such as chloroquine and quinacrine, dependence on the "Jesuit's bark" became a thing of the past.

Unfortunately, the widespread use of these drugs has promoted the evolution of new strains of the parasite that are resistant to the drugs, while the application of pesticides has led to the evolution of mosquito varieties that are resistant to them. The U.S. Army first encountered drug-resistant malaria when it got bogged down in Vietnam.

Malaria is not an easy disease to treat as it manifests several distinct developmental stages in both mosquito and man. Hence a vaccine that is designed to attack one developmental stage may prove useless against the other. In the words of the authors, "the dream of a true vaccine remains elusive." Today, while billions of U.S. dollars are spent on the international space station, very little money is available for the control of diseases, especially those that affect the poor in the Third World. Pharmaceutical companies that put profit over philanthropy are not interested in developing drugs for diseases that affect mainly the poor. But all this may change if malaria were to spread into parts of Europe and the U.S. and strike the rich.

Professor Andrew Spielman and journalist Michael d'Antonio have produced a truly fascinating, highly informative and immensely readable book, aimed at a much wider audience, about a tiny insect that more than any other animal on earth has so adversely and profoundly affected the lives of so many human beings for so long. You may not love the mosquito, but by the time you finish reading the book, you will not fail to develop a deep appreciation for the female of the species.