Mosquito-malaria theory (or sometimes mosquito theory) was a scientific theory developed in the latter half of the 19th century that solved the question of how malaria was transmitted. The theory proposed that malaria was transmitted by mosquitoes, in opposition to the centuries-old medical dogma that malaria was due to bad air, or miasma. The first scientific idea was postulated in 1851 by Charles E. Johnson, who argued that miasma had no direct relationship with malaria. Although Johnson's hypothesis was forgotten, the arrival and validation of the germ theory of diseases in the late 19th century began to shed new lights. [1] When Charles Louis Alphonse Laveran discovered that malaria was caused by a protozoan parasite in 1880, the miasma theory began to subside. [2] [3] [4]
An important discovery was made by Patrick Manson in 1877 that mosquitos could transmit human filarial parasite. [5] Inferring from such novel discovery, Albert Freeman Africanus King proposed the hypothesis that mosquitoes were the source of malaria. [6] In the early 1890s Manson himself began to formulate the complete hypothesis, which he eventually called the mosquito-malaria theory. According to Manson, malaria was transmitted from human to human by a mosquito. [7] [8] The theory was scientifically proved by Manson's confidant Ronald Ross of the Indian Medical Service in the late 1890s. Ross discovered that malaria was transmitted by the biting of specific species of mosquito. [9] For this Ross won the Nobel Prize for Physiology or Medicine in 1902. [10] Further experimental proof was provided by Manson who induced malaria in healthy human subjects from malaria-carrying mosquitoes. [8] Thus the theory became the foundation of malariology and the strategy of control of malaria. [11] [12]
Malaria was prevalent in the Roman Empire, and the Roman scholars associated the disease with the marshy or swampy lands where the disease was particularly rampant. [13] [14] It was from those Romans the name "malaria" originated. They called it malaria (literally meaning "bad air") as they believed that the disease was a kind of miasma that was spread in the air, as originally conceived by ancient Greeks. Since then, it was a medical consensus for centuries that malaria was spread due to miasma, the bad air. However, in medieval West Africa, specifically at Djenné, the people were able to relate mosquitos with malaria. [15]
The first record of argument against the miasmatic nature of malaria was from Irish-American surgeon John Crawford, who wrote an article "Mosquital Origin of Malarial Disease" in Baltimore Observer in 1807, [16] but it provoked no consequences. It was instead ridiculed as impossible, and his work has since been lost. [17] An American physician, Charles Earl Johnson, provided a systematic and elaborate arguments against miasmatic origin of malaria in 1851 before the Medical Society of North Carolina. [18] Some of his important points were: [19]
The notion that malaria was due to miasma was negated by the discovery of malarial parasite. A German physician Johann Heinrich Meckel was the first to observed in 1847 the protozoan parasites which he recognised only as black pigment granules from the blood and spleen of a patient who died of malaria. But he did not understand the parasitic nature and significance of those granules in connection with malaria. In 1849 a German pathologist Rudolf Virchow realised that it could be those granules that were responsible for the disease. In 1879 an Italian biologist Ettore Afanasiev further argued that the granules were definitely the causative agents. [20] [21] [22]
A major discovery was made by a French Army physician Charles Louis Alphonse Laveran working in Algeria, North Africa. At the hospital in Bône (now Annaba), he noticed spherical bodies from a patient's blood film, free or adherent to red blood cells. [23] On 6 November 1880 he observed from one patient's blood the actual living parasite, describing it as "a pigmented spherical body, filiform elements which move with great vivacity, displacing the neighboring red blood cells." He also observed the process of maturation of the parasite (which is now called exflagellation of microgametocytes). He meticulously examined 200 patients, and noted the cellular bodies in all 148 cases of malaria but never in those without malaria. He also found that after treatment with quinine, the parasites disappeared from blood. [24] [25] These findings clearly indicated that the parasite was the cause of malaria, and establishing the germ theory (nature) of malaria. [26] He named the parasite Oscillaria malariae (later renamed Plasmodium malariae ) and reported his discovery to the French Academy of Medicine in Paris on 23 November and 28 December. [27] For his discovery he was awarded the Nobel Prize for Physiology or Medicine in 1907. [2] [28] [29] [30]
In the early 1880s, Laveran's germ theory of malaria was generally accepted by the science community. However pivotal problems still remained, such as what transmit the malarial parasites and how. The scientific clue emerged when a British medical officer Patrick Manson discovered for the first time that parasites were transmitted by mosquitoes. In 1877 while working in Amoy, a coastal town in China, he found that the mosquito Culex fatigans (now Culex quinquefasciatus ) was the vector of the filarial roundworm that he called Filaria sanguinis hominis (but now Wuchereria bancrofti ). His findings were published in the China Customs Medical Report in 1878, [31] and relayed by Spencer Cobbold to the Linnean Society in London. [32] This was the first direct evidence that mosquitoes could transmit microscopic parasites in humans, further suggesting that the same could be true in case of malaria. [5] [33]
Based on the report of Manson's discovery, an American physician Albert Freeman Africanus King developed a proposition that malaria is transmitted by mosquitoes. [1] He revealed his idea in 1881 to his colleagues C.V. Riley and L.O. Howard, who did not share the same opinion. Unfettered he developed the theory with proper justifications and presented it before the Philosophical Society of Washington on 10 February 1882, under the title "The Prevention of Malarial Disease Illustrating inter alia the Conservative Function of Ague". He went so far as to suggest the complete covering of Washington, DC along the Washington Monument with giant net to protect the city from malaria. [6] His idea was ridiculed as inconceivable as scientist still believed malarial parasite was spread through inhalation or ingestion from air (still not far from the miasma theory). [4] He did not give up, and instead formed a more elaborate argument which he published as a 15-page article in the September 1883 issue of The Popular Science Monthly , [34] [35] making an introduction as: [36]
I now propose to present a series of facts... with regard to the so-called “malarial poison,” and to show how they may be explicable by the supposition that the mosquito is the real source of the disease, rather than the inhalation or cutaneous of a marsh-vapor.
King carefully selected his view in 19 points. [37] [38] To paraphrase his lengthy arguments: occurrence of malaria always coincided with conditions that are also ideal for mosquitos, such as in the time of day, geographical area, temperature, and climate. But the flaw in his proposition was that he believed malaria was transmitted by mosquito through its eggs. [4]
In 1889 Patrick Manson returned to England and worked at the Seamen's Hospital Society and also as lecturer on tropical diseases in St George's Hospital at London in 1882. His attention was soon drawn towards malaria and began to realise the implications of his own discovery of filarial transmission on malaria. [5] He strongly supported Laveran's germ theory of malaria, which was not yet completely embraced by the entire medical community of the time. He proposed that:
Manson was unfortunate that he could not investigate his theory as he was not in malaria endemic country such as India, where it could be experimentally proven. But fortunately he met a British army surgeon Ronald Ross, who was on vacation while serving in the Indian Medical Service in India. [40] [41] In November 1894, he revealed to Ross with his hands on Ross' shoulders, saying, "Do you know, I have formed the theory that mosquitoes carry malaria just as they carry filaria." [4]
Manson formally published his theory in the 8 December 1894 issue of the British Medical Journal . Under the title "On the Nature and Significance of Cresenteric and Flagellated bodies in Malarial Blood", he stated:
[The] mosquito, having been shown to be the agent by which the filaria is removed from the human blood vessels, this or similar suctorial agent must be the agent which removes from the human blood vessels those forms of the malaria organism which are destined to continue the existence of this organism outside the body. It must, therefore, be in this or in a similar suctorial insect or insects that the first stages of the extracorporeal life of the malaria organism are passed... [The] hypothesis I have ventured to formulate seems so well grounded that I for one, did circumstances permit, would approach its experimental demonstration with confidence. The necessary experiments cannot for obvious reasons be carried out in England, but I would commend my hypothesis to the attention of medical men in India and elsewhere, where malarial patients and suctorial insects abound. [42]
In 1894 Patrick Manson devised an ingenious procedure for detecting malarial parasites at different developmental stages from blood samples. [43] This would later prove to be the tool for experimental proof of his theory. Manson demonstrated to and taught Ronald Ross the technique from which Ross became convinced of Laveran's germ theory. Trained and mentored by Manson, Ross returned to India in March 1895 to start his investigation. But to the dismay of Ross it was not an easy task. His first detection of malarial parasite from patients came only after two months of hard work. [44] The disappointed Ross had to be encouraged by Manson calling the study as the "Holy Grail" of malaria research, and that Ross was the "Sir Galahad". [4]
After one and half years he made no significant progress. On 20 August 1897 he made a momentous discovery that some mosquitoes had malarial parasites in them. He had fed the blood of a malarial patient (Husein Khan) to different groups of mosquitoes four days before, and found that only one type (which he called "brown type" or more commonly "dappled-winged mosquitoes", not knowing the species, which in fact was Anopheles ) acquired the malarial parasites in its stomach. [45] [46] This was the first evidence for Manson's theory that mosquito did carry the malarial parasite, and Ross would later famously call 20 August as "Malaria Day" (now adopted as World Mosquito Day). [47] [48] [49] [50]
The second experimental evidence came in the mid-1898 when Ross demonstrated the transmission of bird malaria Proteosoma relictum (now Plasmodium relictum ) between larks and mosquitoes, which he called "grey mosquitos" (which were Culex fatigans, but now renamed Culex quinquefasciatus ). [51] [52] [53] He showed that the mosquitoes ingested the parasites from infected birds and could infect healthy birds. He further discovered that the parasites developed in the stomach wall and were later stored in salivary glands of the mosquito. [54] [55] This was a conclusive evidence that malarial parasites were indeed transmitted by mosquitoes. [11] In his report Ross concluded that:
These observations prove the mosquito theory of malaria as expounded by Dr Patrick Manson.
On 9 July 1898 Ross wrote Manson:
Q.E.D. and [I] congratulate you on the mosquito theory indeed.
Ross' scientific evidences were soon fortified by Italian biologists including Giovanni Battista Grassi, Amico Bignami, and Giuseppe Bastianelli, who discovered that human malarial parasite was transmitted by the actual biting (disproving one of Manson's hypotheses) of female mosquito. In 1899 they reported the infection of Plasmodium falciparum with the mosquito Anopheles claviger [12] However the practical importance of validating the theory, i.e. control of mosquito vector should be an effective management strategy for malaria, was not realised by the medical community and the public. Hence in 1900 Patrick Manson clinically demonstrated that the bite of infected anopheline mosquitoes invariably resulted in malaria. [39] He acquired carefully reared infected mosquitoes from Bignami and Bastianelli in Rome. His volunteer at the London School of Tropical Medicine, P. Thurburn Manson gave a detailed account of his malarial fevers and treatment after bitten by the mosquitoes. As he summarised, Manson's clinical trial showed that the practical solution to malaria infection was in:
Malaria is a mosquito-borne infectious disease that affects vertebrates and Anopheles mosquitoes. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquito vector is itself harmed by Plasmodium infections, causing reduced lifespan.
Sir Ronald Ross was a British medical doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on the transmission of malaria, becoming the first British Nobel laureate, and the first born outside Europe. His discovery of the malarial parasite in the gastrointestinal tract of a mosquito in 1897 proved that malaria was transmitted by mosquitoes, and laid the foundation for the method of combating the disease.
Charles Louis Alphonse Laveran was a French physician who won the Nobel Prize in Physiology or Medicine in 1907 for his discoveries of parasitic protozoans as causative agents of infectious diseases such as malaria and trypanosomiasis. Following his father, Louis Théodore Laveran, he took up military medicine as his profession. He obtained his medical degree from University of Strasbourg in 1867.
Plasmodium is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of Plasmodium species involve development in a blood-feeding insect host which then injects parasites into a vertebrate host during a blood meal. Parasites grow within a vertebrate body tissue before entering the bloodstream to infect red blood cells. The ensuing destruction of host red blood cells can result in malaria. During this infection, some parasites are picked up by a blood-feeding insect, continuing the life cycle.
Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer and is classified as a Group 2A (probable) carcinogen.
Carlos Justiniano Ribeiro Chagas, or Carlos Chagas, was a Brazilian sanitary physician, scientist, and microbiologist who worked as a clinician and researcher. Most well known for the discovery of an eponymous protozoal infection called Chagas disease, also called American trypanosomiasis, he also discovered the causative fungi of the pneumocystis pneumonia. He described the two pathogens in 1909, while he was working at the Oswaldo Cruz Institute in Rio de Janeiro, and named the former Trypanosoma cruzi to honour his friend Oswaldo Cruz.
Giovanni Battista Grassi was an Italian physician and zoologist, best known for his pioneering works on parasitology, especially on malariology. He was Professor of Comparative Zoology at the University of Catania from 1883, and Professor of Comparative Anatomy at Sapienza University of Rome from 1895 until his death. His first major research on the taxonomy and biology of termites earned him the Royal Society's Darwin Medal in 1896.
Theodor Albrecht Edwin Klebs was a German-Swiss microbiologist. He is mainly known for his work on infectious diseases. His works paved the way for the beginning of modern bacteriology, and inspired Louis Pasteur and Robert Koch. He was the first to identify a bacterium that causes diphtheria, which was called Klebs–Loeffler bacterium. He was the father of physician Arnold Klebs.
Sir Patrick Manson was a Scottish physician who made important discoveries in parasitology, and was a founder of the field of tropical medicine. He graduated from University of Aberdeen with degrees in Master of Surgery, Doctor of Medicine and Doctor of Law. His medical career spanned mainland China, Hong Kong, Taiwan and London. He discovered that filariasis in humans is transmitted by mosquitoes. This is the foundation of modern tropical medicine, and he is recognized with an epithet "Father of Tropical Medicine". This also made him the first person to show pathogen transmission by a blood-feeding arthropod. His discovery directly invoked the mosquito-malaria theory, which became the foundation in malariology. He eventually became the first President of the Royal Society of Tropical Medicine and Hygiene. He founded the Hong Kong College of Medicine for Chinese and the London School of Hygiene & Tropical Medicine.
Avian malaria is a parasitic disease of birds, caused by parasite species belonging to the genera Plasmodium and Hemoproteus. The disease is transmitted by a dipteran vector including mosquitoes in the case of Plasmodium parasites and biting midges for Hemoproteus. The range of symptoms and effects of the parasite on its bird hosts is very wide, from asymptomatic cases to drastic population declines due to the disease, as is the case of the Hawaiian honeycreepers. The diversity of parasites is large, as it is estimated that there are approximately as many parasites as there are species of hosts. As research on human malaria parasites became difficult, Dr. Ross studied avian malaria parasites. Co-speciation and host switching events have contributed to the broad range of hosts that these parasites can infect, causing avian malaria to be a widespread global disease, found everywhere except Antarctica.
Amico Bignami was an Italian physician, pathologist, malariologist and sceptic. He was professor of pathology at Sapienza University of Rome. His most important scientific contribution was in the discovery of transmission of human malarial parasite in the mosquito.
Angelo Celli was an Italian physician, hygienist, parasitologist and philanthropist known for his pioneering work on the malarial parasite and control of malaria. He was Professor of Hygiene at the University of Palermo, and then at the Sapienza University of Rome. He founded the Pasteur Institute of Italy. With his wife Anna Fraentzel he established a number of medical schools in the Roman Campagna and dispensaries in Rome. He and Ettore Marchiafava correctly described the protozoan parasite that caused malaria and gave it the scientific name Plasmodium in 1885. Understanding the nature of malaria, he was among the first scientists to advocate and work for eradication of insects to prevent infectious diseases. He was elected to the Senate of the Kingdom of Italy in 1892.
Ettore Marchiafava was an Italian physician, pathologist and neurologist. He spent most of his career as professor of medicine at the University of Rome. His works on malaria laid down the foundation for modern malariology. He and Angelo Celli were the first to elucidate living malarial parasites in human blood, and able to distinguish the protozoan parasites responsible for tertian and benign malaria. In 1885 they gave the formal scientific name Plasmodium for these parasites. They also discovered meningococcus as the causative agent of cerebral and spinal meningitis. Marchiafava was the first to describe syphilitic cerebral arteritis and degeneration of brain in an alcoholic patient, which is now eponymously named Marchiafava's disease. He gave a complete description of a genetic disease of blood now known Paroxysmal nocturnal hemoglobinuria or sometimes Strübing-Marchiafava-Micheli syndrome, in honour of the pioneer scientists. He was personal physician to three successive popes and also to House of Savoy. In 1913 he was elected to Senate of the Kingdom of Italy. He founded the first Italian anti-tuberculosis sanatorium at Rome. He was elected member of the Accademia dei Lincei, becoming its vice-president in 1933.
The history of malaria extends from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent except Antarctica. Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the Plasmodium parasites which cause it, research attention has focused on their biology as well as that of the mosquitoes which transmit the parasites.
Sir Ronald Ross Institute of Parasitology is a malaria research institute located in Begumpet, Secunderabad, Hyderabad, India. Established in 1955, the institute is a division of Osmania University. The institute is named after Sir Ronald Ross, winner of Nobel Prize for Physiology or Medicine, 1902.
George Carmichael Low was a Scottish parasitologist.
The Manson Medal, named in honour of Sir Patrick Manson, is the highest accolade the Royal Society of Tropical Medicine and Hygiene awards. Started in 1923, it is awarded triennially to an individual whose contribution to tropical medicine or hygiene is deemed worthy by the council.
William George MacCallum was a Canadian-American physician and pathologist. He was of Scottish descent and was born in Dunnville village in Canada, where his father was a physician. He was educated at the University of Toronto. He graduated with BA in 1894. Initially inclined towards Greeks as academic career, his father influenced him to enter medicine. He joined the second year of the first batch of medicine course in the Johns Hopkins Medical School, and became one of the first graduates of the institute in 1897. He was appointed assistant resident of pathology of the medical school in 1897, resident pathologist in 1901, soon after Associate Professor, and full Professor in 1908. Between 1909 and 1917 he held a twin position of Professor of Pathology at Columbia University and the NewYork–Presbyterian Hospital. From 1917 to 1943 he held the Chair of Pathogy at Johns Hopkins University.
Dmitri Leonidovich Romanowsky was a Russian physician who is best known for his invention of an eponymous histological stain called Romanowsky stain. It paved the way for the discovery and diagnosis of microscopic pathogens, such as malarial parasites, and later developments of new histological stains that became fundamental to microbiology and physiology.
The Sleeping Sickness Commission was a medical project established by the British Royal Society to investigate the outbreak of African sleeping sickness or African trypanosomiasis in Africa at the turn of the 20th century. The outbreak of the disease started in 1900 in Uganda, which was at the time a protectorate of the British Empire. The initial team in 1902 consisted of Aldo Castellani and George Carmichael Low, both from the London School of Hygiene and Tropical Medicine, and Cuthbert Christy, a medical officer on duty in Bombay, India. From 1903, David Bruce of the Royal Army Medical Corps and David Nunes Nabarro of the University College Hospital took over the leadership. The commission established that species of blood protozoan called Trypanosoma brucei, named after Bruce, was the causative parasite of sleeping sickness.
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