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India Currents gave me a voice in days I was very lost. Having my articles selected for publishing was very validating – Shailaja Dixit, Executive Director, Narika, Fremont

Engage! – Discussions on active involvement in personal health and global wellness.

Malaria has been a global reality for centuries, although in present times it is largely endemic to tropical climates and swampy locales. As its name suggests it was first associated with bad-smelling, presumably swampy, air (mal-aria; Italian). The complexities of the life cycle of the malarial parasite took several centuries to research, along with the fact that it is spread to humans by blood-sucking mosquitoes, which in turn need stagnant water or swampy lands to lay their eggs, develop and multiply. 

Malaria has been recorded in ancient Indian writings dating back to the 8th century in the Vedic period and these medical writings seem to have made the connection between mosquitoes and this illness. Other ancient civilizations including Mesopotamian, Chinese, Egyptian, and Greek have documented cyclical fevers coupled with enlargement of the spleen, and associations of occurrence of the illness with particular times of the year. The disease was rampant in large settlement groups especially as they pioneered habitations in wet regions such as the Gangetic plains in India and the Yangtze River valley in China.

Malaria is thought to have arrived in the US with the ships of the conquistadors, and with the import of slaves from West Africa. Malaria was also a constant companion in wars and took an unbiased toll on enemies of both warring sides, including in the American Civil War of the 1860s. 

Portrait of Charles Louis Alphonse Laveran.

In more contemporary times, the relevance of this disease for humanity is documented by the number of Nobel prizes it has garnered. Charles Laveran noticed while treating febrile soldiers in the Franco-Prussian war that their blood cells underwent a cycle of four stages. He teamed up with Camillo Golgi to study these stages and their correlation with the cyclical nature of the disease, and these inquiries led to the discovery of the causative organism of malaria, the protozoan Plasmodium. For his efforts, Laveran was awarded the Nobel prize in 1907. 

Ronald Ross is credited with proving the connection between malaria and mosquitoes and this earned him the Nobel prize in 1902, although an Italian group headed by Giovanni Grassi also claimed this discovery. Ross performed his initial research in Secunderabad (in present-day Telangana in India), where he dissected an endless stream of mosquitoes of Anopheles, Culex, and Aedes species to try and find evidence of infected human blood. He concluded that the malarial parasite was able to grow in Anopheles mosquitoes, and continued his work in Calcutta where he showed these mosquitoes were able to transmit malaria in birds.

Grassi obtained similar results while working in the swampy Italian marshes, and was able to show transmission of the parasite by mosquitoes in humans. This controversial award to Ross was further complicated by the fact that Patrick Manson contributed appreciably to Ross’s success as his mentor, with his earlier experience and knowledge gained by working on a related disease, filariasis, and the role of mosquitoes in its transmission. 

This ecosystem of competition among Nobel prize-winning humans is mirrored in the lives of these parasites. A study of microbe wars within the human body garnered yet another lesser-known Nobel prize. In the early 20th century neurosyphilis formed an appreciable percentage of patients in psychiatric wards. This was an advanced stage of syphilis which was incurable at that time, and involved paralysis of these patients in conjunction with dementia or psychosis. Julius Wagner-Jauregg, an Austrian psychiatrist, showed that infecting patients with malaria cured the syphilis that they were suffering from, and for this, he won the Nobel in 1927.

The curative power of high fever for psychiatric conditions had been anecdotally observed in several cultures, but two aspects of the use of malaria to induce this fever were attractive. The high cyclical fever caused by malaria was desired, and the fact that malaria itself could be cured with quinine when the ‘treatment’ was complete. Further research showed that the bacterium which causes syphilis could not survive high body temperatures, thus causing miraculous recoveries. The subsequent discovery of antibiotics allowed safer treatments of syphilis. 

Indeed the malarial parasite has been shown to affect the immune system of the infected individual in a manner that modulates susceptibility to other infectious agents. This phenomenon known as pathocoenosis is obvious in regions where plague and cholera are endemic, but has also been seen to modulate other bacterial and viral diseases. In fact, this interaction of microbes confounds the expected symptoms of each disease presenting a challenge for diagnoses. 

This photomicrograph of a blood smear contains a macro and microgametocyte of the Plasmodium falciparum parasite. Both macro- and microgametocytes are products of the erythrocytic life cycle. Within a few minutes after the Anopheles sp. vector ingests the gametocytes, microgametocytes develop into microgametes, which are able to fertilize gametes.

Malaria remains a health problem in India, Indonesia, and other countries in Southeast Asia, and is also still a public health concern in Africa. Vaccines have been only partially effective because Plasmodium has evolved an extremely complex lifecycle where its development involves time spent within blood cells and liver of its human host, and in the salivary gland of the mosquito. Symptomatic and asymptomatic forms of the disease are being monitored and treated in India with the goal of eradicating malaria by 2030.

While the asymptomatic disease can modulate the manifestation of other infectious diseases, the resistance of the parasite to anti-malarial drugs is also an emerging consideration. Geography, terrain, and accessibility to patients and treatment are issues in some regions of the country, and simple solutions such as the use of mosquito nets and the introduction of fish that eat mosquito larvae in water bodies are of help. A quirky historical fact is that the British took to the prophylactic consumption of quinine while in India by creating ‘tonic water’ which they mixed with gin as an evening cocktail. Malaria is largely eradicated in the USA and the limited cases seen are largely due to travelers from Africa and Southeast Asia. However, the presence of the asymptomatic disease may complicate this picture. 

L. Iyengar has lived and worked in India and the USA. A scientist by training, she enjoys experiencing diverse cultures, ideas, and writing. Her short story will be included in an anthology showcasing a group of international women writers, to be published in 2021 by The Nasiona. She can be found on Twitter at @l_iyengar.