Who discovered malaria?
Edwin Klebs
Klebs made some significant errors about infectious diseases. He believed, for example, that malaria was caused by a bacterium. In 1879, Corrado Tommasi-Crudeli and he claimed that they isolated a bacterium from the waters of Pontine Marshes in Roman Campagna. They concluded that the bacterium was the pathogen for malaria as they discovered it from damp soil in the region of malaria epidemics. They gave it the name "Bacillus malariae". They further experimented with the bacterial isolate which they injected into rabbits. They observed that infected rabbits developed fever and enlarged spleen, characteristics of malaria. They proposed that the malarial bacterium was transmitted by drinking contaminated water or inhalation from air. Klebs reported that antimalarial drug quinine killed the germ. The discovery was supported by leading malariologists of the time. It was then declared that the malaria problem was solved. When a French Army physician Charles Alphonse Laveran correctly discovered in 1880 that malaria was caused by a protozoan parasite (which he called "Oscillaria malariae", now "Plasmodium falciparum"), the discovery was ignored in preference of the bacillus theory of Klebs and Tommasi-Crudeli. An American physician, though, George Miller Sternberg, proved that the bacillus did not cause specific symptoms of malaria in 1881. The bacillus theory was eventually proved wrong by the experimental demonstration of the mosquito-malaria theory in 1898.
J. B. S. Haldane
In 1949, Haldane proposed that genetic disorders in humans living in malaria-endemic regions provided a phenotype with immunity to blood-borne haemophiles. He noted that mutations expressed in red blood cells, such as sickle-cell anemia and various thalassemias, were prevalent only in tropical regions where malaria has been endemic. He further observed that these were favourable traits for natural selection which protected individuals from receiving malarial infection. This concept of resistance to malaria was eventually confirmed by Anthony C. Allison in 1954.
Plasmodium knowlesi
In 1965, the first case of a naturally occurring infection of "knowlesi" malaria in humans was reported in a 37-year-old male who worked as a surveyor for the U.S. Army Map Service. After carrying out a short trip to peninsular Malaysia, he traveled to Thailand, where he began to feel ill. Although the infecting parasite was initially identified as "P. falciparum", one day later it was then identified as "P. malariae" and it was only confirmed to be "P. knowlesi" after infected blood was used to inoculate rhesus monkeys. In observing the local population where the infection took place, Dr. G. Robert Coatney and other researchers found that they were regularly exposed to the parasite, and, further, were joint hosts of the parasite along with the local monkey populations. This observation led Coatney to declare that monkey malaria is a “true zoonosis.” Prior to arranging the surveyor’s treatment, Coatney had samples of his blood sent back to his lab in Atlanta, where they would be used to infect human prison volunteer inmates and monkeys. A second report emerged in 1971 about the natural infection of a man in Malaysia with "Plasmodium knowlesi" followed by the description of a large focus of human infections in the Kapit Division of Sarawak, Malaysian Borneo. This was made possible due to the development of molecular detection assays which could differentiate between "Plasmodium knowlesi" and the morphologically similar "Plasmodium malariae." Since 2004, there has been an increasing number of reports of the incidence of "P. knowlesi" among humans in various countries in South East Asia, including Malaysia, Thailand, Singapore, the Philippines, Vietnam, Myanmar and Indonesia.
Carl Warburg
Carl Warburg (c. 1805–1892), also known as Charles Warburg, was a physician and scientist. He was the inventor of 'Warburg's Tincture', a medicine well known in the 19th century for treating fevers, including malaria.
History of malaria
Austrian chemist Othmar Zeidler is credited with the first synthesis of DDT (DichloroDiphenylTrichloroethane) in 1874. The insecticidal properties of DDT were identified in 1939 by chemist Paul Hermann Müller of Geigy Pharmaceutical. For his discovery of DDT as a contact poison against several arthropods, he was awarded the 1948 Nobel Prize in Physiology or Medicine. In the fall of 1942, samples of the chemical were acquired by the United States, Britain and Germany. Laboratory tests demonstrated that it was highly effective against many insects.
Angelo Celli
In 1880 with Ettore Marchiafava Celli studied a new protozoan discovered by Alphonse Laveran from the blood of malarial patients. Subsequently it was shown to be the causative agent of malaria. He studied the biology and pathogenesis of malarial plasmodium for years after this working with Ettore Marchiafava, Amico Bignami, Giovanni Battista Grassi and Giuseppe Bastianelli. They were the first to use proper staining (with methylene blue) to identify malarial parasite as distinct blue-coloured pigments in the blood cells. They showed that the parasites lived inside blood cell, and that they divide by simple splitting (fission). They were the first to recognize several the stages of development of the malarial parasite in human blood. They called the new microorganism "Plasmodium" in 1885. Their works helped to differentiate different types of malaria as a result of infection with different species of "Plasmodium".
Giovanni Battista Grassi
Giovanni Battista Grassi (27 March 1854 – 4 May 1925) was an Italian physician and zoologist, most well 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 scientific contributions covered embryological development of honey bees, on helminth parasites, the vine parasite phylloxera, on migrations and metamorphosis in eels, and on termites. He was the first to describe and establish the life cycle of the human malarial parasite, "Plasmodium falciparum", and discovered that only female anopheline mosquitoes are capable of transmitting the disease. His works in malaria remain a lasting controversy in the history of Nobel Prizes, because a British army surgeon Ronald Ross, who discovered the transmission of malarial parasite in birds was given the 1902 Nobel Prize in Physiology or Medicine. But Grassi, who demonstrated the complete route of transmission of human "Plasmodium", and correctly identified the types of malarial parasite as well as the mosquito vector, "Anopheles claviger", was denied.
Amico Bignami
Bignami theorised in 1896 that the mosquito can be the vector of the disease. To show this, he captured mosquitoes in areas with high incidence of malaria and had them bite healthy people. But, like Sir Ronald Ross, a British Army surgeon working in India on the same mission (following Patrick Manson's mosquito-malaria theory), he failed to find direct evidence. In August 1897, Ross discovered malarial parasites inside the mosquito, which indicated that the mosquito was the carrier. In 1898, Bignami, Giovanni Battista Grassi, Antonio Dionisi and Giuseppe Bastianelli's experiments succeeded. Bignami did not hesitate to be bitten himself and to contract the disease. The three scientists presented on November 28, 1898 the results of their observations to the Accademia dei Lincei. Bignami's major works include "Ricerche sull’anatomia patologica delle perniciose" (1890), "Sulle febbre malariche estivo-automnali"(1892) or "On Summer-Autumnal Fevers" (1894), "La malaria e le zanzare" (1899), "La infezione malarica" (1902) and with Grassi, "Ciclo evolutivo della semilune nell' Anopheles claviger" (1899).
History of malaria
In 1834, in British Guiana, a German physician, Carl Warburg, invented an antipyretic medicine: 'Warburg's Tincture'. This secret, proprietary remedy contained quinine and other herbs. Trials were made in Europe in the 1840s and 1850s. It was officially adopted by the Austrian Empire in 1847. It was considered by many eminent medical professionals to be a more efficacious antimalarial than quinine. It was also more economical. The British Government supplied Warburg's Tincture to troops in India and other colonies.
History of malaria
Efforts to control the spread of malaria suffered a major setback in 1930: entomologist Raymond Corbett Shannon discovered imported disease-bearing "Anopheles gambiae" mosquitoes living in Brazil (DNA analysis later revealed the actual species to be "A. arabiensis"). This species of mosquito is a particularly efficient vector for malaria and is native to Africa. In 1938, the introduction of this vector caused the greatest epidemic of malaria ever seen in the New World. However, complete eradication of "A. gambiae" from northeast Brazil and thus from the New World was achieved in 1940 by the systematic application of the arsenic-containing compound Paris green to breeding places, and of pyrethrum spray-killing to adult resting places.
Vasily Danilewsky
Danilewsky was the first to describe the bird malaria. He discovered the symptoms of malaria in birds such as acute anaemia, enlargement of liver and spleen, accumulation of pigments in the blood cells. He also gave the first clue to the similarity of malaria of birds to that of humans. (This idea was followed by Ronald Ross in 1898 who won the Nobel Prize for Physiology or Medicine in 1902 for experimentally demonstrating the principle.) He identified the bird malaria parasites as "pseudovacules", and by 1885 he recognised for the first the existence of three separate genera of protozoan parasites in birds, now known as "Plasmodium", "Haemoproteus" and "Leucocytozoon". However his publication was in Russian and therefore was not accessible to outside Russia, until they were translated into French in a three-volume book "La Parasitologie Comparée du Sang" in 1889.
Plasmodium
"Plasmodium" was first identified when Charles Louis Alphonse Laveran described parasites in the blood of malaria patients in 1880. He named the parasite "Oscillaria malariae". In 1885, zoologists Ettore Marchiafava and Angelo Celli reexamined the parasite and termed it a member of a new genus, "Plasmodium", named for the resemblance to the multinucleate cells of slime molds of the same name. The fact that several species may be involved in causing different forms of malaria was first recognized by Camillo Golgi in 1886. Soon thereafter, Giovanni Batista Grassi and Raimondo Filetti named the parasites causing two different types of human malaria "Plasmodium vivax" and "Plasmodium malariae". In 1897, William Welch identified and named "Plasmodium falciparum". This was followed by the recognition of the other two species of "Plasmodium" which infect humans: "Plasmodium ovale" (1922) and "Plasmodium knowlesi" (identified in long-tailed macaques in 1931; in humans in 1965). The contribution of insect hosts to the "Plasmodium" life cycle was described in 1897 by Ronald Ross and in 1899 by Giovanni Batista Grassi, Amico Bignami and Giuseppe Bastianelli.
History of malaria
Dutch physician Pieter Pel first proposed a tissue stage of the malaria parasite in 1886, presaging its discovery by over 50 years. This suggestion was reiterated in 1893 when Golgi suggested that the parasites might have an undiscovered tissue phase (this time in endothelial cells). Pel in 1896 supported Golgi's latent phase theory.
List of Plasmodium species
It is known from many written historical sources that "P. vivax" malaria was endemic in the wetlands of England from the 1500s until the 20th century. It is suspected that this disease was introduced by the Romans sometime before 400 AD. It seems likely that it remained endemic in these areas at least up to 1000 AD.
Ettore Marchiafava
Marchiafava first developed his first research interest in pathology from Robert Koch, whom he met in Berlin during his doctoral course. He studied malaria intensively for eleven years, from 1880 to 1891. With Angelo Celli, in 1880, he confirmed a new protozoan (then called "Oscillaria malariae") discovered by Alphonse Laveran, finding it in the blood of the many patients suffering from malaria fever. They were the first to use proper staining (with methylene blue) to identify malarial parasite as distinct blue-coloured pigments in the blood cells. They showed that the parasites lived inside blood cell, and that they divide by simple splitting (fission). They were the first to recognize several the stages of development of the malarial parasite in human blood. They called the new microorganism "Plasmodium" in 1885. Their works helped to differentiate different types of malaria as a result of infection with different species of "Plasmodium". With Amico Bignami he published a classic monograph "On Summer-Autumnal Fevers" in 1892, which was translated into English in 1894. This was a major foundation in modern malariology. They reported the direct evidence of mosquito theory that mosquitoes transmit malaria.
Malaria
Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by single-celled microorganisms belonging to the "Plasmodium" group. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected 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 disease is most commonly transmitted by an infected female "Anopheles" mosquito. The mosquito bite introduces the parasites from the mosquito's saliva into a person's blood. The parasites travel to the liver where they mature and reproduce. Five species of "Plasmodium" can infect and be spread by humans. Most deaths are caused by "P. falciparum" because "P. vivax", "P. ovale", and "P. malariae" generally cause a milder form of malaria. The species "P. knowlesi" rarely causes disease in humans. Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests. Methods that use the polymerase chain reaction to detect the parasite's DNA have been developed, but are not widely used in areas where malaria is common due to their cost and complexity.
The risk of disease can be reduced by preventing mosquito bites through the use of mosquito nets and insect repellents, or with mosquito control measures such as spraying insecticides and draining standing water. Several medications are available to prevent malaria in travellers to areas where the disease is common. Occasional doses of the combination medication sulfadoxine/pyrimethamine are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria. Despite a need, no effective vaccine exists, although efforts to develop one are ongoing. The recommended treatment for malaria is a combination of antimalarial medications that includes an artemisinin. The second medication may be either mefloquine, lumefantrine, or sulfadoxine/pyrimethamine. Quinine along with doxycycline may be used if an artemisinin is not available. It is recommended that in areas where the disease is common, malaria is confirmed if possible before treatment is started due to concerns of increasing drug resistance. Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistant "P. falciparum" has spread to most malarial areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia.
The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator. This includes much of Sub-Saharan Africa, Asia, and Latin America. In 2016, there were 216 million cases of malaria worldwide resulting in an estimated 445,000 to 731,000 deaths. Approximately 90% of both cases and deaths occurred in Africa. Rates of disease have decreased from 2000 to 2015 by 37%, but increased from 2014 during which there were 198 million cases. Malaria is commonly associated with poverty and has a major negative effect on economic development. In Africa, it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and negative effects on tourism.
John P. Woodall
At the Entebbe Lab, Woodall and a colleague made the first isolation of the o'nyong'nyong virus in 1959 during a large outbreak of a disease that appeared initially to be either dengue or chikungunya fever. They later found evidence that the presence of o'nyong'nyong fever seemed to affect the development of the malaria parasite, reducing malaria transmission rates. The o'nyong'nyong virus and the malarial parasite share a common vector, two species of anopheline mosquitoes. Woodall also conducted early research on the Zika virus in the early 1960s, about the time the virus was being confirmed as a cause of human disease.
Timeline of malaria
Malaria is an infectious disease caused by a parasite; it is spread by the bite of an infected mosquito. Every year, 300 to 700 million people get infected. Malaria kills 1 million to 2 million people every year. 90% of the deaths occur in Africa.
William Trager
William Trager (20 March 1910, Newark, New Jersey – 22 January 2005) was an American parasitologist. Trager was noted for his research of malaria.
British Raj
Fevers ranked as one of the leading causes of death in India in the 19th century. Britain's Sir Ronald Ross, working in the Presidency General Hospital in Calcutta, finally proved in 1898 that mosquitoes transmit malaria, while on assignment in the Deccan at Secunderabad, where the Centre for Tropical and Communicable Diseases is now named in his honour.
History of malaria
Molecular methods have confirmed the high prevalence of "P. falciparum" malaria in ancient Egypt. The Ancient Greek historian Herodotus wrote that the builders of the Egyptian pyramids (circa 2700–1700 BCE) were given large amounts of garlic, probably to protect them against malaria. The Pharaoh Sneferu, the founder of the Fourth dynasty of Egypt, who reigned from around 2613–2589 BCE, used bed-nets as protection against mosquitoes. Cleopatra VII, the last Pharaoh of Ancient Egypt, similarly slept under a mosquito net. However, whether the mosquito nets were used for the purpose of malaria prevention, or for more mundane purpose of avoiding the discomfort of mosquito bites, is unknown. The presence of malaria in Egypt from circa 800 BCE onwards has been confirmed using DNA-based methods.
Plasmodium knowlesi
In 1960, American parasitologist Don E. Eyles and his supervisor, G. Robert Coatney (1902–1990) worked under the National Institutes of Health to carry out experiments on rhesus macaques in a Memphis laboratory with the assumption that humans were not susceptible to “monkey malaria.” Early research had concluded that macaques could not host "Plasmodium vivax", the human malaria parasite. This led Eyles and Coatney to begin working with "Plasmodium cynomolgi", a parasite similar enough to "P. vivax" to model the human malaria infection. The two exposed themselves to the infection, noting the causal itchy bite as a mere annoyance; however, Eyles fell ill with fever soon after the experiment. It was not until several days later that the two accepted the possibility that Eyles may have contracted malaria. Examination of blood films would confirm that it was in fact possible to contract “monkey malaria.”
History of malaria
The coastal plains of southern Italy fell from international prominence when malaria expanded in the sixteenth century. At roughly the same time, in the coastal marshes of England, mortality from "marsh fever" or "tertian ague" ("ague": via French from medieval Latin "acuta" ("febris"), acute fever) was comparable to that in sub-Saharan Africa today. William Shakespeare was born at the start of the especially cold period that climatologists call the "Little Ice Age", yet he was aware enough of the ravages of the disease to mention it in eight of his plays.
Plasmodium falciparum
The species originated from the malarial parasite "Laverania" found in gorillas, around 10,000 years ago. Alphonse Laveran was the first to identify the parasite in 1880, and named it "Oscillaria malariae". Ronald Ross discovered its transmission by mosquito in 1897. Giovanni Battista Grassi elucidated the complete transmission from a female anopheline mosquito to humans in 1898. In 1897, William H. Welch created the name "Plasmodium falciparum", which ICZN formally adopted in 1954. "P. falciparum" assumes several different forms during its life cycle. The human-infective stage are sporozoites from the salivary gland of a mosquito. The sporozoites grow and multiply in the liver to become merozoites. These merozoites invade the erythrocytes (RBCs) to form trophozoites, schizonts and gametocytes, during which the symptoms of malaria are produced. In the mosquito, the gametocytes undergo sexual reproduction to a zygote, which turns into ookinete. Ookinete forms oocyts from which sporozoites are formed.
Ann Bishop (biologist)
Her best known work was a comprehensive study of "Plasmodium", the malaria parasite, and investigation of various chemotherapies for the disease. Later she studied drug resistance in this parasite, research that proved valuable to the British military in World War II. She discovered the potential for cross-resistance in these parasites during that same period. Bishop also discovered the protozoan "Pseudotrichomonas keilini" and worked with "Aedes aegypti", a malaria vector, as part of her research on the disease. Elected to the Royal Society in 1959, Bishop was the founder of the British Society for Parasitology and served on the World Health Organization's Malaria Committee.
History of malaria
In 1848, German anatomist Johann Heinrich Meckel recorded black-brown pigment granules in the blood and spleen of a patient who had died in a mental hospital. Meckel was thought to have been looking at malaria parasites without realizing it; he did not mention malaria in his report. He hypothesized that the pigment was melanin. The causal relationship of pigment to the parasite was established in 1880, when French physician Charles Louis Alphonse Laveran, working in the military hospital of Constantine, Algeria, observed pigmented parasites inside the red blood cells of malaria sufferers. He witnessed the events of exflagellation and became convinced that the moving flagella were parasitic microorganisms. He noted that quinine removed the parasites from the blood. Laveran called this microscopic organism "Oscillaria malariae" and proposed that malaria was caused by this protozoan. This discovery remained controversial until the development of the oil immersion lens in 1884 and of superior staining methods in 1890–1891.
Giovanni Maria Lancisi
Giovanni Maria Lancisi (26 October 1654 – 20 January 1720) was an Italian physician, epidemiologist and anatomist who made a correlation between the presence of mosquitoes and the prevalence of malaria. He was also known for his studies about cardiovascular diseases, and is remembered in the eponymous Lancisi's sign.
History of malaria
Malaria became widely recognized in ancient Greece by the 4th century BCE, and is implicated in the decline of many city-state populations. The term "μίασμα" (Greek for miasma): "stain, pollution", was coined by Hippocrates of Kos who used it to describe dangerous fumes from the ground that are transported by winds and can cause serious illnesses. Hippocrates (460–370 BCE), the "father of medicine", related the presence of intermittent fevers with climatic and environmental conditions and classified the fever according to periodicity: Gk.:"tritaios pyretos" / L.:"febris tertiana" (fever every third day), and Gk.:"tetartaios pyretos" / L.:"febris quartana" (fever every fourth day).
Benjamin Cabrera
Focusing on his major, Dr. Cabrera published more than a hundred scientific studies concerning medical parasitology and public health. He also developed innovations in drug treatments against diseases caused by mosquitoes and agricultural soil. In 1961, together with Lee M. Howard, he made the first field study of simian malaria in the Philippines, and found that malaria occurred in 8.6 percent of the animals tested. Although the study was very limited, the report suggested that the simian reservoir of malaria is probably of limited significance for the human population in the Philippines.
Malaria prophylaxis
Malaria is one of the oldest known pathogens, and began having a major impact on human survival about 10,000 years ago with the birth of agriculture. The development of virulence in the parasite has been demonstrated using genomic mapping of samples from this period, confirming the emergence of genes conferring a reduced risk of developing the malaria infection. References to the disease can be found in manuscripts from ancient Egypt, India and China, illustrating its wide geographical distribution. The first treatment identified is thought to be Quinine, one of four alkaloids from the bark of the Cinchona tree. Originally it was used by the tribes of Ecuador and Peru for treating fevers. Its role in treating malaria was recognised and recorded first by an Augustine monk from Lima, Peru in 1633. Seven years later the drug had reached Europe and was being used widely with the name 'the Jesuit's bark'. From this point onwards the use of Quinine and the public interest in malaria increased, although the compound was not isolated and identified as the active ingredient until 1820. By the mid-1880s the Dutch had grown vast plantations of cinchona trees and monopolised the world market.
Anopheles claviger
"An. claviger" was experimentally used to discover the transmission of human malarial parasite "P. falciparum", along with the fact that only female anophelines can transmit malaria. Before 1898 it was not known how malaria was transmitted. The Italian biologist Giovanni Battista Grassi started investigating different mosquito species in the early 1898 on the basis of mosquito-malaria theory. He suspected that only certain species were involved in transmission of malaria. In September Battista reported the presence of malarial parasite in "An. claviger" indicating it as malaria vector. Battista performed human experimentation on Abele Sola, who had been a patient for six years in the Hospital of the Holy Spirit (Ospedale di Santo Spirito in Sassia) in Rome. With mutual consent Sola was bitten by malaria-infected mosquitoes for ten nights, and after few weeks he was down with tertian malaria. Battista and his colleagues Amico Bignami, Giuseppe Bastianelli and Ettore Marchiafava continued to demonstrate the same experiments in other patients and were always successful. In November they found the parasites on the gut wall of the infected mosquitoes. "P. falciparum"-carrying mosquito was no doubt the causative vector of malaria. They formally announced the discovery at the session of the Accademia dei Lincei on 4 December 1898. This experiment further established that "An. claviger" is the sole mosquito species responsible for human malaria in Italy, and other European countries. (In other parts of the world other species of "Anopheles" are responsible.) In addition the discovery laid the foundation for prevention of malaria by vector control of mosquitoes.
Thorselliaceae
The first described species was "Thorsellia anophelis". It was isolated from the midgut of the malaria mosquito "Anopheles arabiensis" from Kenya. This new bacterium was given its name after the Swedish researcher Walborg Thorsell who worked with mosquitoes and insecticides against mosquitoes for many years. "Thorsellia" bacteria have now been found in mosquito species that are the major vectors of malaria in Africa, Asia and South America. The bacteria have also been found in the waters where the malaria mosquitoes breed. Some properties of "Thorsellia" suggest that they are adapted to the mosquito guts, they can accept an alkaline pH, which is found in mosquito larvae and they grow faster in blood culture. However, "T. anophelis" has also been found in the reproductive tissues of male and female "Anopheles gambiae" and "An". "coluzzii" mosquitoes.
Leonard White (physician)
Here is the letter that Dr. Theobald Smith wrote to Dr. White as "health officer" at Uxbridge. 
In 1889 and 1893, Dr. Theobald Smith made discoveries which implicated cattle ticks as the necessary developmental host of the causal agent of Texas cattle fever. The question of what caused malaria and how it was transmitted did not escape his attention. In 1896, he wrote this letter to one Dr. White of Uxbridge, Massachusetts which was in the midst of a malaria outbreak.
Dr. Willard Van Orsdel King House
Starting in 1917 King worked with Leland Ossian Howard at a field laboratory the latter established in Mound, Louisiana. He worked for the United States Bureau of Entomlology there for the next 13 years. An important aspect of King's work was that although his field was entomology he published in medical journals, so his research results would reach medical scientists. King found that particular species of mosquitoes were efficient hosts for the parasite that causes malaria. His work guided malaria control efforts in the southeast United States. This included a mosquito surveillance and control program for military camps during World War II.
Sociology of health and illness
There are many diseases that affect South America, but two major conditions are malaria and Hepatitis D.
Malaria affects every country in South America except Uruguay, Chile, and The Falkland Islands. Elevation is a major factor in the areas where malaria is found. The disease is spread from person to person via mosquito bites. People are typically bitten by mosquitoes at dusk and dawn. Symptoms of this disorder are: high fever, chills, sweating, headaches, body aches, weakness, vomiting and diarrhea. If left untreated, new symptoms can occur; people that are infected may experience seizures, delirium and coma. Severe cases may end in death. Malaria can be cured, but the symptoms may not become noticeable until months later. There are three forms of medication that can cure Malaria. An infected person's accessibility to these drugs is dependent upon their access to medical care and their financial situation. Literature about Malaria treatment typically is focused toward people who are tourists. Most sources are not written with the native in mind.
The first sign of Hepatitis D was detected in 1978 when a strange and unrecognizable internuclear antigen was discovered during a liver biopsy of several Italians who suffered HBV infection. Scientists initially thought that it was an antigenic specificity of HBV, but they soon found that it was a protein from another disease altogether. They called it "Hepatitis Delta Virus" (HDV). This new virus was found to be defective. HDV needed HBV to act as a helper function in order for it to be detected. Normally Hepatitis B is transmitted through blood or any type of blood product. In South America Hepatitis D was found to be fatal. Scientists are still unsure in what way this disease was being transmitted throughout certain South American countries. Sexual contact and drug use are the most common means of transmission. HDV is still considered an unusual form of hepatitis. Agents of this virus resemble that of plant viroids. It is still hard to tell how many stereotypes exist because HDV is under the umbrella of HBV. HDV causes very high titers in the blood of people who are infected. Incubation of Hepatitis D typically lasts for thirty five days. Most often Hepatitis D is a co-infection with Hepatitis B or a super-infection with chronic hepatitis. In terms of super infections there are high mortality rates, ranging seventy to eighty percent; in contrast with co-infections which have a one to three percent mortality rate. There is little information with the ecology of Hepatitis D. Epidemics have been found in Venezuela, Peru, Columbia, and Brazil. People who are treated for Hepatitis B have been able to control Hepatitis D. People who have chronic HDB will continue to get HDV.
Parasitology
Modern parasitology developed in the 19th century with accurate observations by several researchers and clinicians. In 1828, James Annersley described amoebiasis, protozoal infections of the intestines and the liver, though the pathogen, "Entamoeba histolytica", was not discovered until 1873 by Friedrich Lösch. James Paget discovered the intestinal nematode "Trichinella spiralis" in humans in 1835. James McConnell described the human liver fluke in 1875. A physician at the French naval hospital at Toulon, Louis Alexis Normand, in 1876 researching the ailments of French soldiers returning from what is now Vietnam, discovered the only known helminth that, without treatment, is capable of indefinitely reproducing within a host and causes the disease strongyloidiasis. Patrick Manson discovered the life cycle of elephantiasis, caused by nematode worms transmitted by mosquitoes, in 1877. Manson further predicted that the malaria parasite, "Plasmodium", had a mosquito vector, and persuaded Ronald Ross to investigate. Ross confirmed that the prediction was correct in 1897–1898. At the same time, Giovanni Battista Grassi and others described the malaria parasite's life cycle stages in "Anopheles" mosquitoes. Ross was controversially awarded the 1902 Nobel prize for his work, while Grassi was not.
Michael Thomas Gillies
Michael Thomas (Mick) Gillies (15 September 1920 – 10 December 1999) 
was an English medical entomologist. He spent most of his working life in the tropics, particularly Tanzania (then known as Tanganyika) and later The Gambia, studying the transfer of malaria between mosquitos and humans. He was awarded the Chalmers and Christophers Medals for his seminal contribution to the understanding of the role of mosquito behaviour in the transfer of malaria. He was also a world authority on the mayfly.
Human genetic resistance to malaria
Evolutionary biologist J.B.S. Haldane was the first to give a hypothesis on the relationship between malaria and the genetic disease. He first delivered his hypothesis at the Eighth International Congress of Genetics held in 1948 at Stockholm on a topic "The Rate of Mutation of Human Genes". He formalised in a technical paper published in 1949 in which he made a prophetic statement: "The corpuscles of the anaemic heterozygotes are smaller than normal, and more resistant to hypotonic solutions. It is at least conceivable that they are also more resistant to attacks by the sporozoa which cause malaria." This became known as 'Haldane's malaria hypothesis', or concisely, the 'malaria hypothesis'.
Hillel Yaffe
Yaffe's first efforts to eradicate malaria focused on drying the swamps. He used many methods, including wide use of eucalyptus trees, on the principle that the large tree would draw a lot of water from the ground. Also, manual efforts were undertaken to dry the swamps. The residents of Hadera and foreign workers from Africa (who arrived after Yaffe requested help from Baron Rothschild) began the physically demanding labor of drying the swamps using a wide network of canals, connecting the swamps to the Hadera Stream. Another approach taken by Yaffe was research. Yaffe left for Europe and learned novel theories about malaria. Among these studies was one that suggested that mosquitoes from the genus Anopheles, which were prevalent in swamps, were carriers of the disease. He began to plead with farmers to hang canopies around the beds, nets around the windows, and to clean every pool of standing water. Likewise, Yaffe convinced Baron Rothschild to send men to kill the mosquitoes. Afterward the incidence of malaria decreased, and efforts to dry the swamps continued with greater force. Forestation of large areas near Hadera with eucalyptus trees was part of Yaffe's effort to change the environment in order to respond comprehensively to the disease.
Giovanni Battista Grassi
In 1895 he was appointed professor of comparative anatomy at Sapienza University of Rome, where he would spend the rest of his life. He joined Angelo Celli, Amico Bignami, Giuseppe Bastianelli and Ettore Marchiafava, who were working on malaria in districts around Rome. Grassi was the group’s entomologist. The group announced at the session of the Accademia dei Lincei on 4 December 1889 that a healthy man in a non-malarial zone had contracted tertian malaria after being bitten by an experimentally infected "Anopheles claviger". Between 1900 and 1902, Grassi, Gustavo Pittaluga and Giovanni Noè made intensive studies of malaria at Agro Portuense, at Fiumicino, on the Tiber, and on the plain of Capaccio, near Paestum.
London School of Hygiene &amp; Tropical Medicine
It was initially located at the Albert Dock Seamen's Hospital in the London Docklands. Just prior to this teaching in tropical medicine had been commenced in 1899 at the Extramural school at Edinburgh and even earlier at London's Livingstone College founded in 1893 by Charles F. Harford-Battersby (1865–1925). Before giving lectures at St George's Hospital, London, in 1895, Livingstone College afforded Manson his first opportunity to teach courses in tropical medicine. Manson's early career was as a physician in the Far East where he deduced the correct etiology of filariasis, a parasitic vector based disease, transmitted through the bite of a mosquito. On his return to London, he was appointed Medical Advisor to the Colonial Office. He strongly believed that doctors should be trained in tropical medicine to treat British colonial administrators and others working throughout Britain's tropical empire. He also encouraged and mentored Ronald Ross during this period to uncover the correct etiology of malaria, which Ross subsequently discovered in 1897, winning the Nobel Prize for his efforts. The original school was established as part of the Seamen's Hospital Society.
Meir Yoeli
Yoeli is best known for his study and research of malaria at New York University. He developed the technique for testing rodent malaria parasites that was used on experimental research for chemotherapy and immunology. Before Yoeli's breakthrough, malaria research of parasites could only be done on human volunteers or monkeys. In 1974, Yoeli and his colleague, Bruce Hargreaves, discovered a mutant organism that causes cerebral malaria.
Plasmodium malariae
Malaria has been recognized since the Greek and Roman civilizations over 2,000 years ago, with different patterns of fever described by the early Greeks. In 1880, Alphonse Laveran discovered that the causative agent of malaria is a parasite. Detailed work of Golgi in 1886 demonstrated that in some patients there was a relationship between the 72-hour life cycle of the parasite and the chill and fever patterns in the patient. The same observation was found for parasites with 48-hour cycles. Golgi concluded that there must be more than one species of malaria parasite responsible for these different patterns of infection.
Ronald Ross
Sir Ronald Ross (13 May 1857 – 16 September 1932), 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. He was a polymath, writing a number of poems, published several novels, and composed songs. He was also an amateur artist and natural mathematician. He worked in the Indian Medical Service for 25 years. It was during his service that he made the groundbreaking medical discovery. After resigning from his service in India, he joined the faculty of Liverpool School of Tropical Medicine, and continued as Professor and Chairman of Tropical Medicine of the institute for 10 years. In 1926 he became Director-in-Chief of the Ross Institute and Hospital for Tropical Diseases, which was established in honour of his works. He remained there until his death.
Mehmet Aziz
According to the London newspaper "The Times," the three-year project to eradicate malaria in Cyprus was "largely carried out by the Cypriots themselves under the skilful organization of Mr Mehmed Aziz, the island's chief health inspector, who studied with Sir Ronald Ross." Aziz was the originator of the idea and methodology to eradicate malaria in Cyprus, having studied similar attempts to control the disease in Egypt.
Paul Guttmann
Guttmann also made contributions in his research of tuberculosis and malaria. With Paul Ehrlich (1854-1915), he discovered that the histological stain, methylene blue had effectiveness against malaria.
Y. D. Sharma
During his days at Public Health Research Institute, Sharma was successful in cloning the knob protein gene of "Plasmodium falciparum", one of the protozoan parasites causing malaria, in 1984. At AIIMS, he led a group of researchers who carried out molecular epidemiological studies of the parasites causing malaria and their studies widened the understanding of the parasites' resistance to chloroquine and antifolate drugs. He is credited with the identification of "P. falciparum" strains in India, isolation of "P. falciparum" and "Plasmodium vivax", another non-cultivable protozoan parasite, as well as the development of a genomic library of "Plasmodium vivax". It was his group which reported the first incidence of malaria in humans caused by "Plasmodium knowlesi", a primate malarial parasite. These studies are reported to have relevance in developing immunotherapeutic reagents. His researches have been documented by way of several articles and the online repository of scientific articles of the Indian Academy of Sciences has listed a number of them. His work has been cited by many researchers and he has mentored over 70 master's and doctoral students in their studies.
History of malaria
Relapses were first noted in 1897 by William S. Thayer, who recounted the experiences of a physician who relapsed 21 months after leaving an endemic area. He proposed the existence of a tissue stage. Relapses were confirmed by Patrick Manson, who allowed infected "Anopheles" mosquitoes to feed on his eldest son. The younger Manson then described a relapse nine months after his apparent cure with quinine.
Mosquito-malaria theory
Based on the report of Manson's discovery, an American physician Albert Freeman Africanus King developed a proposition that malaria is transmitted by mosquitoes. 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. 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). 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", making an introduction as:
King carefully selected his view in 19 points. 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.
John William Watson Stephens
There are several species of the protozoan parasite "Plasmodium" that cause malaria in humans. One such species, namely "Plasmodium ovale", was first described in 1914 by Stephens in a blood sample taken from a patient in Pachmarhi, Madhya Pradesh in the autumn of 1913.
Global health
The 19th century held major discoveries in medicine and public health. The Broad Street cholera outbreak of 1854 was central to the development of modern epidemiology. The microorganisms responsible for malaria and tuberculosis were identified in 1880 and 1882, respectively. The 20th century saw the development of preventive and curative treatments for many diseases, including the BCG vaccine (for tuberculosis) and penicillin in the 1920s. The eradication of smallpox, with the last naturally occurring case recorded in 1977, raised hope that other diseases could be eradicated as well.
Meir Yoeli
Meir Yoeli (August 20, 1912 – December 5, 1975) was a biologist, researcher and educator. He is best known for his expertise in the field of infectious and parasitic diseases, which led to advancements in malaria research in the 1960s and 70s. His name inspired the term, "yoelii," the taxonomy of organisms with English names. Yoeli was also a professor at New York University, where he wrote scientific papers on the study of human malaria.
Columbian exchange
European exploration of tropical areas was aided by the New World discovery of quinine, the first effective treatment for malaria. Europeans suffered from this disease, but some indigenous populations had developed at least partial resistance to it. In Africa, resistance to malaria has been associated with other genetic changes among sub-Saharan Africans and their descendants, which can cause sickle-cell disease. In fact, the resistance of sub-Saharan Africans to malaria in the Southern United States contributed to the development of slavery in those regions.
History of malaria
The Chinese "Huangdi Neijing" (The Inner Canon of the Yellow Emperor) dating from ~300 BCE – 200 CE apparently refers to repeated paroxysmal fevers associated with enlarged spleens and a tendency to epidemic occurrence.
Around 168 BCE, the herbal remedy "Qing-hao" () ("Artemisia annua") came into use in China to treat female hemorrhoids ("Wushi'er bingfang" translated as "Recipes for 52 kinds of diseases" unearthed from the Mawangdui).
"Qing-hao" was first recommended for acute intermittent fever episodes by Ge Hong as an effective medication in the 4th-century Chinese manuscript "Zhou hou bei ji fang", usually translated as "Emergency Prescriptions kept in one's Sleeve". His recommendation was to soak fresh plants of the artemisia herb in cold water, wring it out and ingest the expressed bitter juice in its raw state.
History of malaria
The first evidence of malaria parasites was found in mosquitoes preserved in amber from the Palaeogene period that are approximately 30 million years old. Human malaria likely originated in Africa and coevolved with its hosts, mosquitoes and non-human primates. Malaria protozoa are diversified into primate, rodent, bird, and reptile host lineages. Humans may have originally caught "Plasmodium falciparum" from gorillas. "P. vivax", another malarial "Plasmodium" species among the six that infect humans, also likely originated in African gorillas and chimpanzees. Another malarial species recently discovered to be transmissible to humans, "P. knowlesi", originated in Asian macaque monkeys. While "P. malariae" is highly host specific to humans, there is some evidence that low level non-symptomatic infection persists among wild chimpanzees.
Malaria
The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine. This tree grows on the slopes of the Andes, mainly in Peru. The indigenous peoples of Peru made a tincture of cinchona to control fever. Its effectiveness against malaria was found and the Jesuits introduced the treatment to Europe around 1640; by 1677, it was included in the London Pharmacopoeia as an antimalarial treatment. It was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by the French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou.
Quinine
The Jesuits were the first to bring cinchona to Europe. The Spanish were aware of the medicinal properties of cinchona bark by the 1570s or earlier: Nicolás Monardes (1571) and Juan Fragoso (1572) both described a tree that was subsequently identified as the cinchona tree and whose bark was used to produce a drink to treat diarrhea. Quinine has been used in unextracted form by Europeans since at least the early 17th century. It was first used to treat malaria in Rome in 1631. During the 17th century, malaria was endemic to the swamps and marshes surrounding the city of Rome. Malaria was responsible for the deaths of several popes, many cardinals and countless common Roman citizens. Most of the priests trained in Rome had seen malaria victims and were familiar with the shivering brought on by the febrile phase of the disease. The Jesuit brother Agostino Salumbrino (1564–1642), an apothecary by training who lived in Lima, observed the Quechua using the bark of the cinchona tree for that purpose. While its effect in treating malaria (and malaria-induced shivering) was unrelated to its effect in controlling shivering from rigors, it was a successful medicine against malaria. At the first opportunity, Salumbrino sent a small quantity to Rome for testing as a malaria treatment. In the years that followed, cinchona bark, known as Jesuit's bark or Peruvian bark, became one of the most valuable commodities shipped from Peru to Europe. When King Charles II was cured of malaria at the end of the 17th Century with quinine, it became popular in London. It remained the antimalarial drug of choice until the 1940s, when other drugs took over.
Disease in colonial America
The cause of malaria was unknown until the late 19th century. Colonial physicians attributed it to "miasma" or bad air. In reality this disease is a parasite that is found in certain species of mosquitoes, which bred more rapidly as virgin soil was broken in the Carolina lowlands for rice cultivation. The parasite found the slaves as a reservoir for the infection of the mosquito. The mosquito then transmitted the parasite to other slaves and the white population, causing rapid development of highly malarious communities. The disease spread across the South and Northwest. People who newly arrived from Europe were especially vulnerable to the deadly forms, but after the second generation, the colonists typically suffered non-fatal cases, characterized by a feverish season for a few weeks every year.
Dapsone
In the early 20th century, the German chemist Paul Ehrlich was developing theories of selective toxicity based largely on the ability of certain dyes to kill microbes. Gerhard Domagk, who would later win a Nobel Prize for his efforts, made a major breakthrough in 1932 with the discovery of the antibacterial prontosil red (sulfonamidochrysoidine). Further investigation into the involved chemicals opened the way to sulfa drug and sulfone therapy, first with the discovery of sulfanilamide, the active agent of prontosil, by Daniel Bovet and his team at Pasteur Institute (1935), then with that of dapsone independently by Ernest Fourneau in France and Gladwin Buttle in the United Kingdom.
The spread of drug-resistant malaria in Africa has encouraged the development of new, low-cost antimalarial drugs. "Plasmodium falciparum", one of the "Plasmodium" species that causes malaria, has developed resistance both to chloroquine and sulfadoxine/pyrimethamine, two of the most common treatments for malaria. Artemisinin, another antimalarial drug, had been developed in the 1980s but was too expensive for large-scale use. This led GlaxoSmithKline to develop Lapdap, a combination drug consisting of chlorproguanil and dapsone. Lapdap was licensed in the United Kingdom starting in October 2003.
History of malaria
William Henry Perkin, a student of August Wilhelm von Hofmann at the Royal College of Chemistry in London, unsuccessfully tried in the 1850s to synthesize quinine in a commercial process. The idea was to take two equivalents of N-allyltoluidine () and three atoms of oxygen to produce quinine () and water. Instead, Perkin's mauve was produced when attempting quinine total synthesis via the oxidation of N-allyltoluidine. Before Perkin's discovery, all dyes and pigments were derived from roots, leaves, insects, or, in the case of Tyrian purple, molluscs.
History of malaria
The first successful continuous malaria culture was established in 1976 by William Trager and James B. Jensen, which facilitated research into the molecular biology of the parasite and the development of new drugs. By using increasing volumes of culture medium, "P.falciparum" was grown to higher parasitemia levels (above 10%).
Manuel Elkin Patarroyo
Manuel Elkin Patarroyo (born November 3, 1946) is a Colombian Professor of Pathology and Immunology who made the world's first attempt to create a synthetic vaccine against a parasite called the protozoa Plasmodium falciparum that causes severe malaria, a disease that causes of death (~1.5 million people per year) in tropical and subtropical regions, including parts of the Americas, Asia, and Africa.
Mosquito-malaria theory
On 9 July 1898 Ross wrote Manson:
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" 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. 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:
History of malaria
Artemisinin was isolated by pharmacologist Tu Youyou (Nobel Prize in Physiology or Medicine, 2015). Tu headed a team tasked by the Chinese government with finding a treatment for choloroquine-resistant malaria. Their work was known as Project 523, named after the date it was announced – 23 May 1967. The team investigated more than 2000 Chinese herb preparations and by 1971 had made 380 extracts from 200 herbs. An extract from qinghao ("Artemisia annua") was effective but the results were variable. Tu reviewed the literature, including "Zhou hou bei ji fang" (A handbook of prescriptions for emergencies) written in 340 BC by Chinese physician Ge Hong. This book contained the only useful reference to the herb: "A handful of qinghao immersed with two litres of water, wring out the juice and drink it all." Tu's team subsequently isolated a nontoxic, neutral extract that was 100% effective against parasitemia in animals. The first successful trials of artemisinin were in 1979.
Effects of global warming on human health
Malaria is a mosquito-borne parasitic disease that infects humans and other animals caused by microorganisms in the Plasmodium family. It begins with a bite from an infected female mosquito, which introduces the parasite through its saliva and into the infected host's circulatory system. It then travels through the bloodstream into the liver where it can mature and reproduce. The disease causes symptoms that typically include fever, headache, shaking chills, anemia, and in severe cases can progress to coma or death.
Malaria and the Caribbean
For example, before this time of exploration and travel, the Caribbean natives of the islands had never been exposed to malaria. Therefore, when the Europeans and African slaves began to inhabit the islands, the natives were greatly affected by it and died in astonishing numbers. Due to their genetics, the African slaves had somewhat of an advantage over the white, wealthy settlers: partial immunity was present to falciparum malaria. This malaria affected children and immigrants on some islands but not all. One contracts this disease by being bitten by an Anopheles mosquito which can be found on Africa and the Americas. Falciparum malaria sickens the human by attacking the human’s red blood cells and the parasite remains within the victim’s body for life which allows the cycle to continue. This malaria affected predominantly the adult European voyagers rather than predominantly the African slaves.
Ogobara Doumbo
Ogobara Doumbo (1 January 1956 – 9 June 2018) was a Malian medical researcher at the University of Mali. He was recognised as a global leader in malaria research. He was the recipient of the Chevalier de l’, Legion d'honneur and research award on Malaria in Africa.
Hillel Yaffe
Yaffe became a noted authority on malaria, its prevention and its cure. He published many articles and even lectured in Paris in an international conference on malaria in 1900. He worked to improve public health and studied other illnesses which had spread throughout the region, with an emphasis on prevention and minimizing contagious spreading of diseases. In 1902, an epidemic of cholera spread through Israel. Yaffe was appointed by the Turkish government to combat the epidemic. He decided that people were forbidden to leave their communities, and that it was forbidden to enter or leave the house of a sick person, in order to stop the illness from spreading. The epidemic was stopped.
Hemozoin
Black-brown pigment was observed by Johann Heinrich Meckel in 1847, in the blood and spleen of a person suffering from insanity. However, it was not until 1849 that the presence of this pigment was connected to infection with malaria. Initially, it was thought that this pigment was produced by the body in response to infection, but Charles Louis Alphonse Laveran realized in 1880 that "malaria pigment" is, instead, produced by the parasites, as they multiplied within the red blood cell. The link between pigment and malaria parasites was used by Ronald Ross to identify the stages in the "Plasmodium" life cycle that occur within the mosquito, since, although these forms of the parasite are different in appearance to the blood stages, they still contain traces of pigment.
Dr EA Koch Memorial
This memorial immortalises the work of pioneering Cairns doctor Edward Albert Koch, in particular his treatment of malaria and early recognition of the role played by mosquitoes in transmitting the disease. Dr Koch's fever remedy and preventative measures played a significant role in controlling endemic malaria in far North Queensland in the late 19th century and first half of the 20th century.
Jane M. Carlton
Carlton is among a group of scientists , recording and categorizing changes in all of the malaria parasite’s genes at once,with a view toward detecting drug resistance in its earliest stages while it can still be controlled, finding new vulnerabilities in the parasite’s genome that can be exploited to fight malaria. As Faculty Director of Genomic Sequencing at NYU’s Center for Genomics and Systems Biology, Carlton is examining the genomes of dozens of malaria isolates at a time. Recently her group sequenced several genomes from both a human malaria species ("P. vivax") and a closely related monkey malaria parasite ("Plasmodium cynomolgi"), producing a more detailed picture of malaria evolution and uncovering a surprising amount of genetic variety in the latter.
History of malaria
In 1885, Ettore Marchiafava, Angelo Celli and Camillo Golgi studied the reproduction cycles in human blood (Golgi cycles). Golgi observed that all parasites present in the blood divided almost simultaneously at regular intervals and that division coincided with attacks of fever. In 1886 Golgi described the morphological differences that are still used to distinguish two malaria parasite species "Plasmodium vivax" and "Plasmodium malariae". Shortly after this Sakharov in 1889 and Marchiafava & Celli in 1890 independently identified "Plasmodium falciparum" as a species distinct from "P. vivax" and "P. malariae". In 1890, Grassi and Feletti reviewed the available information and named both "P. malariae" and "P. vivax" (although within the genus "Haemamoeba".) By 1890, Laveran's germ was generally accepted, but most of his initial ideas had been discarded in favor of the taxonomic work and clinical pathology of the Italian school. Marchiafava and Celli called the new microorganism "Plasmodium". "H. vivax" was soon renamed "Plasmodium vivax". In 1892, Marchiafava and Bignami proved that the multiple forms seen by Laveran were from a single species. This species was eventually named "P. falciparum". Laveran was awarded the 1907 Nobel Prize for Physiology or Medicine "in recognition of his work on the role played by protozoa in causing diseases".
Plasmodium falciparum erythrocyte membrane protein 1
Malaria is the deadliest among infectious diseases, accounting for approximately 429,000 human deaths in 2015 as of the latest estimate by the World Health Organization. In humans, malaria can be caused by five "Plasmodium" parasites, namely "P. falciparum", "P. vivax", "P. malariae", "P. ovale" and "P. knowlesi". "P. falciparum" is the most dangerous species, attributed to >99% of malaria's death toll, with 70% of these deaths occurring in children under the age of five years. The parasites are transmitted through the bites of female mosquitos (of the species of "Anopheles"). Before invading the RBCs and causing the symptoms of malaria, the parasites first multiply in the liver. The daughter parasites called merozoites then only infect the RBCs. They undergo structural development inside the RBCs, becoming trophozoites and schizonts. It is during this period that malarial symptoms are produced. Unlike RBCs infected by other "Plasmodium" species, "P. falciparum"-infected RBCs had been known to spontaneously stick together. By the early 1980s, it was established that when the parasite (both the trophozoite and schizont forms) enters the blood stream and infects RBCs, the infected cells form knobs on their surface. Then they become sticky, and get attached to the walls (endothelium) of the blood vessels through a process called cytoadhesion, or cytoadherence. Such attachment favours binding with and accumulation of other RBCs. This process is known as sequestration. It is during this condition that the parasites induce an immune response (antigen-antibody reaction) and evade destruction in the spleen. Although the process and significance of sequestration were described in detail by two Italian physicians Amico Bignami and Ettore Marchiafava in the early 1890s, it took a century to discover the actual factor for the stickiness and virulence.
Louis-Daniel Beauperthuy
Louis-Daniel Beauperthuy (25 August 1808 – 3 September 1871) was a French physician who made important contributions to the study of the causes of infectious diseases such as yellow fever, malaria, and leprosy. He was the first to systematically argue that malaria and yellow fever were transmitted by mosquitos.
Blackwater fever
Blackwater fever is a complication of malaria infection in which red blood cells burst in the bloodstream (hemolysis), releasing hemoglobin directly into the blood vessels and into the urine, frequently leading to kidney failure. The disease was first linked to malaria by the Sierra Leonean physician Dr John Farrell Easmon in his 1884 pamphlet entitled "The Nature and Treatment of Blackwater Fever." Easmon coined the name "blackwater fever" and was the first to successfully treat such cases following the publication of his pamphlet.
Gustavo Pittaluga (doctor)
Gustavo Pittaluga Fattorini (1876 in Florence, Italy – 1956 in Havana, Cuba) was an Italian doctor and biologist.Nationalized Spanish in 1904 Pittaluga made contributions to the development of haematology and the parasitology, as well as by his contributions to national and international fight against malaria and other protozoans causing diseases. Pittaluga studied medicine in the University of Rome, where he became a doctor in 1900 with a thesis on acromegaly. Although he had become interested in psychiatry a subject in which he never lost the interest he became the assistant of the doctor and naturalist Giovanni Battista Grassi, a specialist in the zoology of invertebrates and protozooans. Grassi was the one of the team (including Pittaluga) who demonstrated that malaria is transmitted by mosquitos of the genus Anopheles.
Abdoulaye Djimdé
Djimdé earned a doctorate in pharmacy in 1988 at the University of Bamako. He opened his own pharmacy and realised that people needed more effective methods to treat malaria. He began to volunteer with Ogobara Doumbo at the new Malaria Research and Training Centre, and moved to the University of Maryland, Baltimore County to complete a PhD. He worked with the National Institutes of Health and identified the first molecular marker of chloroquine resistant malaria. During his PhD he joined the American Society of Tropical Medicine and Hygiene.
Leonard White (physician)
Dr. Leonard White's house was in Uxbridge, on Douglas Street, next to where Snowling Rd is located today. White was an example of a 19th-century physician, a country doctor, who published, and who served as a local health officer, under the Massachusetts State Board of Health. His contributions were significant in the history of medicine and public health. He was a contemporary of Walter Reed, who contributed in 1885 to the same publication in which Dr. White's case reports of childhood vaccine related deaths appeared. Walter Reed unlocked answers to Yellow fever in the late 19th century. The first notion of a connection of mosquitoes transmitting diseases was from a Cuban physician, Carlos Finlay in 1881 relating to Finlay's work with Yellow fever, later confirmed specifically for malaria by Ronald Ross in India circa 1898. Malaria is a protozoan disease carried by "aedes aegypti" mosquitoes, as a "vector".
History of malaria
"Plasmodium knowlesi" has been known since the 1930s in Asian macaque monkeys and as experimentally capable of infecting humans. In 1965 a natural human infection was reported in a U.S. soldier returning from the Pahang Jungle of the Malaysian peninsula.
Malaria
"Plasmodium vivax" was used between 1917 and the 1940s for malariotherapy—deliberate injection of malaria parasites to induce a fever to combat certain diseases such as tertiary syphilis. In 1927, the inventor of this technique, Julius Wagner-Jauregg, received the Nobel Prize in Physiology or Medicine for his discoveries. The technique was dangerous, killing about 15% of patients, so it is no longer in use.
Charles Wilberforce Daniels
Charles Wilberforce Daniels FRCP (1862–1927) was a British physician and pioneer of tropical medicine, known for his confirmation of Ronald Ross's 1898 discovery of the role of mosquito-vectored malarial parasites in avian malaria.
Elizabeth A. Winzeler
From 2007 to 2012, Winzeler headed the Department of Cellular Biology at the Genomics Institute of the Novartis Research Foundation. From 2010 to 2012, she was also Associate Professor in the Department of Genetics and Department of Immunology & Microbial Science at Scripps Research Institute. In 2012, she became Professor of Pediatrics at University of California, San Diego and Director of Translational Research at the UCSD Heath Sciences Center for Immunity, Infection, and Inflammation.
While she was still at Stanford University she published papers on yeast genomics. In San Diego she has worked extensively with the malaria parasite, both on its genomics and on generating new possible treatments for infections with malaria. "Plasmodium falciparum", the malaria parasite, enters red blood cells of a human host in part of its life cycle and thus protects itself, but Winkeler saw that details of the genome annotation and of the transcriptome (the gene expression viewed as messenger RNAs present) could open new avenues for attack. She used the information her laboratory developed to design high-throughput drug discovery protocols. In addition, Winzeler has discovered the basis of some of the drug resistance mutations in the parasite. The laboratory has discovered several potential malarial treatment drugs, resulting in a $4.7 million dollar grant from the Gates Foundation to continue this work.Elizabeth A Winzeler, Daniel D Shoemaker, Anna Astromoff, Hong Liang, Keith Anderson, Bruno Andre, Rhonda Bangham, Rocio Benito, Jef D Boeke, Howard Bussey, Angela M Chu, Carla Connelly, Karen Davis, Fred Dietrich, Sally Whelen Dow, Mohamed El Bakkoury, Françoise Foury, Stephen H Friend, Erik Gentalen, Guri Giaever, Johannes H Hegemann, Ted Jones, Michael Laub, Hong Liao, Nicole Liebundguth, David J Lockhart, Anca Lucau-Danila, Marc Lussier, Nasiha M'rabet, Patrice Menard, Michael Mittmann, Chai Pai, Corinne Rebischung, Jose L Revuelta, Linda Riles, Christopher J Roberts, Petra Ross-MacDonald, Bart Scherens, Michael Snyder, Sharon Sookhai-Mahadeo, Reginald K Storms, Steeve Véronneau, Marleen Voet, Guido Volckaert, Teresa R Ward, Robert Wysocki, Grace S Yen, Kexin Yu, Katja Zimmermann, Peter Philippsen, Mark Johnston, Ronald W Davis (1999) "Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis” "Science" 285 (5429), 901-906.
Francisco E. Baisas
He pioneered the study of mosquitoes in the Philippines. His taxonomic studies of 71 new species dating back to 1927 enhanced the development of mosquito systematics and established the knowledge base for these winged vectors of the highly infectious tropical disease, malaria. His works contributed greatly to the control of malaria, severe cases of which even today can lead to death - 627,000 in 2012 alone according to the Bill and Melinda Gates Foundation. The first Filipino to be trained as a malaria technician by the International Health Division of the Rockefeller Foundation, Baisas later was employed as an entomologist by the US Army's 3rd General Medical Laboratory and the Philippine's Institute of Malariology under whose auspices he conducted most of his life work. In 1955, the Philippine Government named him among the country's Ten Outstanding Scientists, awarding him a gold medal and a Diploma of Honor for his contributions to the study of malaria and mosquitoes in the Philippines.
History of malaria
The name malaria derived from "mal aria" ('bad air' in Medieval Italian). This idea came from the Ancient Romans who thought that this disease came from the horrible fumes in the swamps. The word malaria has its roots in the miasma theory, as described by historian and chancellor of Florence Leonardo Bruni in his "Historiarum Florentini populi libri XII", which was the first major example of Renaissance historical writing:
Sir Ronald Ross Institute of Parasitology
Sir Ronald Ross was posted as a general duty medical officer to the regiment stationed in Secunderabad in 1893. Though he was a surgeon by qualification, Ross was attracted towards research in tropical diseases, especially malaria. During his posting, he worked on his research from a laboratory in the old Begumpet military hospital building. Built in 1895, this building was surrounded by marshes which proved rather helpful for his research experiments. It was in this building on 20 August 1897 that he made the discovery of the malarial parasite inside the body of a mosquito. His study confirmed that mosquitoes were the carriers of malaria parasite. For his work in demonstrating the life-cycle of the parasites of malaria in mosquitoes, and thus establishing the hypothesis of Laveran and Manson, Ross was awarded the Nobel Prize in 1902.
History of malaria
In 1717, the dark pigmentation of a postmortem spleen and brain was published by the epidemiologist Giovanni Maria Lancisi in his malaria text book "De noxiis paludum effluviis eorumque remediis". This was one of the earliest reports of the characteristic enlargement of the spleen and dark color of the spleen and brain which are the most constant post-mortem indications of chronic malaria infection. He related the prevalence of malaria in swampy areas to the presence of flies and recommended swamp drainage to prevent it.
Samuel Taylor Darling
Samuel Taylor Darling (April 6, 1872 in Harrison, New Jersey – May 21, 1925 in Beirut) was an American pathologist and bacteriologist who discovered the pathogen "Histoplasma capsulatum" in 1906. He died in Beirut in a car accident together with British malariologist Norman Lothian. The 'Darling Prize' for malaria research was established in his memory.
History of malaria
In 1881, Dr. Carlos Finlay, a Cuban-born physician of Scottish ancestry, theorized that yellow fever was transmitted by a specific mosquito, later designated "Aedes aegypti". The theory remained controversial for twenty years until confirmed in 1901 by Walter Reed. This was the first scientific proof of a disease being transmitted exclusively by an insect vector, and demonstrated that control of such diseases necessarily entailed control or eradication of its insect vector.
Lewis Hackett
Hackett had the opportunity to collaborate with the Italian doctor Alberto Missiroli, at the Laboratory of Public Health of Rome, who was interested in the implementation of preventive measures for malaria control based on the control of mosquitoes. Together with Bartholomew Gosio, he founded the School of Malariology in Nettuno. He began to experiment with DDT against Anopheles mosquitoes, vectors of the disease. In 1925, Hackett and Missiroli, with funding from the Rockefeller Foundation, started the work which led to the creation of the Istituto Superiore di Sanità.
Malaria
Malaria is usually confirmed by the microscopic examination of blood films or by antigen-based rapid diagnostic tests (RDT). In some areas, RDTs need to be able to distinguish whether the malaria symptoms are caused by "Plasmodium falciparum" or by other species of parasites since treatment strategies could differ for non-"P. falciparum" infections. Microscopy is the most commonly used method to detect the malarial parasite—about 165 million blood films were examined for malaria in 2010. Despite its widespread usage, diagnosis by microscopy suffers from two main drawbacks: many settings (especially rural) are not equipped to perform the test, and the accuracy of the results depends on both the skill of the person examining the blood film and the levels of the parasite in the blood. The sensitivity of blood films ranges from 75–90% in optimum conditions, to as low as 50%. Commercially available RDTs are often more accurate than blood films at predicting the presence of malaria parasites, but they are widely variable in diagnostic sensitivity and specificity depending on manufacturer, and are unable to tell how many parasites are present.
Ronald Ross
Ronald Ross was awarded a Nobel Prize for his discovery of the life cycle of malarial parasite. He did not build his concept of malarial transmission in humans, but in birds. In 1897, an Italian physician and zoologist Giovanni Battista Grassi, along with his colleagues, had established the developmental stages of malaria parasites in anopheline mosquitoes; and they described the complete life cycles of "P. falciparum", "P. vivax" and "P. malariae" the following year. When the 1902 Nobel Prize for Physiology or Medicine was considered, the Nobel Committee initially intended the prize to be shared between Ross and Grassi, however Ross accused Grassi of deliberate fraud. The weight of favour ultimately fell on Ross, largely due to the influences of Robert Koch, the appointed neutral arbitrator in the committee; as reported, "Koch threw the full weight of his considerable authority in insisting that Grassi did not deserve the honor". Ross was the first to show that malarial parasite was transmitted by the bite of infected mosquitoes, in his case the avian "Plasmodium relictum".
History of malaria
Malaria researchers have won multiple Nobel Prizes for their achievements, although the disease continues to afflict some 200 million patients each year, killing more than 600,000.
Corrado Tommasi-Crudeli
Corrado Tommasi-Crudeli (31 January 1834 to 31 May 1900) was an Italian physician known for his works in pathology and hygiene. He studied for his medical degree at the University of Pisa. He was trained in pathology under the German pathologist Rudolf Virchow. He worked in medical services at Florence, Palermo, and Rome. He was Chair of Pathology at the Sapienza University of Rome. He was known to the public for his service during cholera outbreak and in establishing hospitals, particularly the Institute for Experimental Hygiene (Istituto di Igiene Sperimentale) in Rome. He was elected to Italian Senate during 1892–1893. He, with Edwin Klebs, discovered that typhoid and diphtheria were caused by bacteria. However, they made mistake in declaring that a bacterium (which they called "Bacillus malariae") was also responsible for malaria.
Mosquito-malaria theory
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 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.
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. 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. These findings clearly indicated that the parasite was the cause of malaria, and establishing the germ theory (nature) of malaria. 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. For his discovery he was awarded the Nobel Prize for Physiology or Medicine in 1907.
Science and technology in Venezuela
Louis-Daniel Beauperthuy (Basse-Terre, Guadeloupe, France, August 25, 1808 – Demerara, British Guiana, September 3, 1871) was a Venezuelan-French physician who made important contributions to the study of the causes of infectious diseases such as yellow fever, malaria, and leprosy. He was the first to systematically argue that malaria and yellow fever were transmitted by mosquitos. He studied medicine at the Paris Faculty of Medicine, and obtained his M.D. in 1837. He was immediately appointed by the Paris Museum of Natural History as a "Travelling Naturalist" to work in Orinoco basin, Venezuela. He was one of the earliest scientists to observe microorganism using microscopy in relation to diseases. In 1838 he developed a theory that all infectious diseases were due to parasitic infection with "animalcules" (microorganisms). With the help of his friend M. Adele de Rosseville, he presented his theory in a formal presentation before the French Academy of Sciences in Paris. He suspected that mosquitos were the carriers of the infectious pathogens, including those of leprosy. In 1842 he worked at the Facultad Médica de Caracas (Caracas Medical School). In 1850 he became professor of anatomy at the School of Medicine of the College of Cumana. He was appointed the Director of the Leper Hospital in Demerara in British Guiana, the post he held till his death. By 1853, he was convinced that malaria and yellow fever were spread by mosquitos. He even identified the particular group of mosquitos that transmit yellow fever as the "domestic species" of "striped-legged mosquito", which can be recognised as "Aedes aegypti", the actual vector. He published his theory in 1854 in the "Gaceta Oficial de Cumana" (""Official Gazette of Cumana""). His reports were assessed by an official commission, which discarded his mosquito theory. Only after 1891, with the works of Carlos Finlay, his investigations are reviewed with seriousness. A hospital in Basse-Terre, called the Centre hospitalier Louis-Daniel Beauperthuy, was established in 1959 in his honour.
Ali Maow Maalin
Ali Maow Maalin (also Mao Moallim and Mao' Mo'allim; 1954 – 22 July 2013) was a Somali hospital cook and health worker from Merca who is the last person known to be infected with naturally occurring "Variola minor" smallpox in the world. He was diagnosed with the disease in October 1977 and made a full recovery. Although he had many contacts, none of them developed the disease and an aggressive containment campaign was successful in preventing an outbreak. Smallpox was declared to have been eradicated globally by the World Health Organization (WHO) two years later. Maalin was subsequently involved in the successful poliomyelitis eradication campaign in Somalia, and he died of malaria while carrying out polio vaccinations after the re-emergence of the poliovirus in 2013.
Malaria
In April 1894, a Scottish physician, Sir Ronald Ross, visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research that culminated in 1897 when Ross, who was working in the Presidency General Hospital in Calcutta, proved the complete life-cycle of the malaria parasite in mosquitoes. He thus proved that the mosquito was the vector for malaria in humans by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. For this work, Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius. The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900. Its recommendations were implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.
Gideon Mer
Gideon Mer (, born 1894 in Panevėžys, died 22 March 1961 in Rosh Pinna) was an Israeli scientist whose work was mostly concerned with the eradication of malaria. He was the father of Arna Mer-Khamis and the grandfather of Juliano Mer-Khamis.
Science and technology in Venezuela
Arnoldo Gabaldón (Trujillo, March 1, 1909 – Caracas, September 1, 1990) was a physician, researcher and politician. Graduated in 1928 earned a doctorate in medical sciences at the Universidad Central de Venezuela. In (Germany) completed a specialty at the Institute for Maritime and Tropical Diseases of Hamburg. Later traveling in 1935 to the United States as a fellow of the Rockefeller Foundation to obtain a doctorate from Johns Hopkins University in hygiene sciences with speciality in protozoology. Back in Venezuela he was appointed to head the newly created Special Directorate of Malariology within the Ministry of Health and Welfare, a position he held until 1950. Under the direction of Gabaldón, Venezuela became the first country which organized a nationwide campaign against malaria by using DDT, which led to be the first to achieve eradication of the disease in a large area extension of the tropical zone. He also discovered new species of malarial parasites and devoted himself to studying the mosquito "Anopheles nuneztovari", action that catalyzed the recognition of educational needs and preparing managerial staff of the Ministry of Health, through the creation of the school that bears his name in Maracay, a deep and additional contribution. Between 1959 and 1964 President Rómulo Betancourt appointed him Minister of Health and Welfare and Gabaldón. He was the first professor of the Simón Bolívar Chair of Latin-American Studies at the University of Cambridge, England (1968–69) and directed post-doctoral studies at the Central University of Venezuela. Gabaldón wrote more than 200 papers published in national and international medical journals. Gabaldón was active as an expert of the World Health Organization (WHO) for malaria control in countries from 5 continents.
Tropical medicine
Malaria is a parasitic disease transmitted by an "Anopheles" mosquito to a human host. The parasite that causes malaria belongs to the genus "Plasmodium". Once infected, malaria can take a wide variety of forms and symptoms. The disease is placed into the uncomplicated category or the severe category. If quickly diagnosed and treated, malaria can be cured. However, some of the more serious symptoms, such as acute kidney failure, severe anemia, and acute respiratory distress syndrome can be fatal if not dealt with swiftly and properly. Certain types of "Plasmodium" can leave dormant parasites in the liver that can reawaken months or years later, causing additional relapses of the disease. In the "World Malaria Report" of 2016, the World Health Organization reported a malaria infection rate of 212 million, 90% of which occurred in the African region. However, malaria infection rates had fallen 21% since 2010 at the time of the report. The WHO also reported an estimated mortality rate of 429,000 deaths in the year 2015. The malaria mortality rate had fallen 29% globally since 2010. Children under 5 contract the malaria disease more easily than others, and in the year 2015, an estimated 303,000 children under the age of 5 were killed by malaria. Since the year 2010 however, the mortality rate of children under 5 fell by an estimated 35%.
Artemisinin
"Artemisia annua" is a common herb found in many parts of the world, and has been used by Chinese herbalists for more than 2000 years in the treatment of malaria. The earliest record dates back to 200 BCE, in the "Fifty-two Prescriptions" unearthed from the Mawangdui. Its antimalarial application was first described in "Zhouhou Beiji Fang" ("The Handbook of Prescriptions for Emergencies", ), edited in the middle of the 4th century CE by Ge Hong; in that book, 43 malaria treatment methods were recorded. Images of the original scientific papers that record the history of the discovery, have been available online since 2006.
In 1967, a plant screening research program, under a secret military programme code-named "Project 523", was set up by the People's Liberation Army to find an adequate treatment for malaria; the program and early clinical work were ordered of Mao Zedong at the request of North Vietnamese leaders to provide assistance for their malaria-ridden army. In the course of this research in 1972, Tu Youyou discovered artemisinin in the leaves of "Artemisia annua".