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Created by: Ivana Škrlec
Malaria is a severe disease caused by parasites of the genus Plasmodium, which is transmitted to humans by a bite of an infected female mosquito of the species Anopheles. Malaria remains the leading cause of mortality around the world, and early diagnosis and fast-acting treatment prevent unwanted outcomes. It is the most common disease in Africa and some countries of Asia, while in the developed world malaria occurs as imported from endemic areas. The sweet sagewort plant was used as early as the second century BC to treat malaria fever in China. Much later, quinine started being used as an antimalaria drug. A global battle against malaria started in 1955. The World Health Organization carries out a malaria control program on a global scale, focusing on local strengthening of primary health care, early diagnosis of the disease, timely treatment, and disease prevention. Globally, the burden of malaria is lower than ten years ago. However, in the last few years, there has been an increase in the number of malaria cases around the world. It is moving towards targets established by the WHO, but that progress has slowed down.
Malaria affected an estimated 219 million people causing 435,000 deaths in 2017 globally. This burden of morbidity and mortality is a result of more than a century of global effort and research aimed at improving the prevention, diagnosis, and treatment of malaria [1]. Malaria is the most common disease in Africa and some countries in Asia with the highest number of indigenous cases. The malaria mortality rate globally ranges from 0.3–2.2%, and in cases of severe forms of malaria in regions with tropical climate from 11–30% [2]. Different studies showed that the prevalence of malaria parasite infection has increased since 2015 [3,4].
The causative agent of malaria is a small protozoon belonging to the group of Plasmodium species, and it consists of several subspecies. Some of the Plasmodium species cause disease in human [2,5]. The genus Plasmodium is an amoeboid intracellular parasite which accumulates malaria pigment (an insoluble metabolite of hemoglobin). Parasites on different vertebrates; some in red blood cells, and some in tissue. Of the 172 of Plasmodium species, five species can infect humans. These are P. malariae, P. falciparum, P. vivax, P. ovale, and P. knowlesi. In Southeast Asia, the zoonotic malaria P. knowlesi is recorded. Other species rarely infect humans [5,6,7,8]. All the mentioned Plasmodium species cause the disease commonly known as malaria (Latin for Malus aer—bad air). Likewise, all species have similar morphology and biology [9].
The Plasmodium life cycle is very complex and takes place in two phases; sexual and asexual, the vector mosquitoes and the vertebrate hosts. In the vectors, mosquitoes, the sexual phase of the parasite's life cycle occurs. The asexual phase of the life cycle occurs in humans, the intermediate host for malaria [9,10]. Human malaria is transmitted only by female mosquitoes of the genus Anopheles. The parasite, in the form of sporozoite, after a bite by an infected female mosquito, enters the human blood and after half an hour of blood circulation, enters the hepatocytes [11]. The first phase of Plasmodium asexual development occurs in the hepatocytes, and then in the erythrocytes. All Plasmodium species lead to the rupture of erythrocytes [7,9,12,13].
The most common species in the Americas and Europe are P. vivax and P. malariae, while in Africa it is P. falciparum [14].
Discovery of Malaria
It is believed that the history of malaria outbreaks goes back to the beginnings of civilization. It is the most widespread disease due to which many people have lost lives and is even thought to have been the cause of major military defeats, as well as the disappearance of some nations [15]. The first descriptions of malaria are found in ancient Chinese medical records of 2700 BC, and 1200 years later in the Ebers Papyrus [2]. The military leader Alexander the Great died from malaria [15]. The evidence that this disease was present within all layers of society is in the fact that Christopher Columbus, Albrecht Dürer, Cesare Borgia, and George Washington all suffered from it [16,17].
Although the ancient people frequently faced malaria and its symptoms, the fever that would occur in patients was attributed to various supernatural forces and angry divinities. It is, thus, stated that the Assyrian-Babylonian deity Nergal was portrayed as a stylized two-winged insect, as was the Canaan Zebub ('Beelzebub, in translation: the master of the fly') [17]. In the 4th century BC, Hippocrates described this disease in a way that completely rejected its demonic origins and linked it with evaporation from swamps which, when inhaled, caused the disease. That interpretation was maintained until 1880 and Laveran's discovery of the cause of the disease [18]. Laveran, a French military surgeon, first observed parasites in the blood of malaria patients, and for that discovery, he received the Nobel Prize in 1907 [19].
Cartwright and Biddis state that malaria is considered to be the most widespread African disease [14]. The causative agent of malaria is a small protozoon belonging to the group of Plasmodium species, and it consists of several subspecies [14].
The Development of Diagnostic Tests for Proving Malaria through History
Malaria can last for three and up to five years, if left untreated, and depending on the cause, may recrudesce. In P. vivax and ovale infections, the persistence of the merozoites in the blood or hypnozoites in hepatocytes can cause relapse months or years after the initial infection. Additionally, relapse of vivax malaria is common after P. falciparum infection in Southeast Asia. Relapse cases were observed in P. falciparum infections, which can lead to a rapid high parasitemia with subsequent destruction of erythrocytes [20,21]. Children, pregnant women, immunocompromised and splenectomized patients are especially vulnerable to malaria infection, as well as healthy people without prior contact with Plasmodium. A laboratory test for malaria should always confirm clinical findings. The proving of malaria is carried out by direct methods such as evidence of parasites or parts of parasites, and indirect methods that prove the antibodies to the causative agents (Table 1) [2,5,22].
Table 1. Diagnostic tests for proving malaria.
Direct methods
Microscopic analysis Fast test, cheap Required much experience as well as equipment
Rapid diagnostic tests Quick and simple Less sensitive and accurate, price
Molecular tests Correct determination of type, highly sensitive and accurate Price, long-term in a large number of cases
Indirect methods
Indirect immunofluorescence Specific, sensitive Long time to perform, subjective evaluation of results
ELISA Correct determination of type, specific, sensitive Long time to perform, price
The gold standard method for malaria diagnosis is light microscopy of stained blood films by Giemsa. Due to a lack of proper staining material and trained technicians, this method is not available in many parts of sub-Saharan Africa. The sensitivity of the method depends on the professional expertise, and it is possible to detect an infection with 10–100 parasites/μL of blood. A negative finding in patients with symptoms does not exclude malaria, but smears should be repeated three times in intervals of 12–24 h if the disease is still suspected [23,24]. Diagnosis of malaria using serologic testing has traditionally been done by immunofluorescence antibody testing (IFA). IFA is time-consuming and subjective. It is valuable in epidemiological studies, for screening possible blood donors. It also demands fluorescence microscopy and qualified technicians [23,25,26].
Rapid Diagnostic Tests (RDT) for the detection of antigens in the blood are immunochromatographic tests to prove the presence of parasite antigens. No electrical equipment and no special experience or skills are required to perform these tests. The RDTs are now recommended by WHO as the first choice of test all across the world in all malaria-endemic areas. The sensitivity of the antigen test varies depending on the selected antigens represented in the test. For some RDTs is 50–100 parasites/μL (PfHRP2) to <100 parasites/μL [27,28]. The FDA approved the first RDT test in 2007. It is recommended that the results of all RDT tests should be confirmed by microscopic blood analysis [29]. It is known that antigens detected with RDT test remain in the blood after antimalarial treatment, but the existence of these antigens varies after treatment. The false-positive rates should be less than 10% [30]. Several RDT tests in the eight rounds of testing revealed malaria at a low-density parasite (200 parasites/μL), had low false-positive rates and could detect P. falciparum or P. vivax infections or both [30]. False-positive rates of P. vivax were typically small, between 5% and 15%. On the other hand, the false-positive rates of P. falciparum range from 3–32% [30,31]. Good RDTs might occasionally give false-negative results if the parasite density is low, or if variations in the production of parasite antigen reduce the ability of the RDT to detect the parasite. False negative results of the RDT test for P. falciparum ranged between 1% and 11% [31,32,33,34]. The overall sensitivity of RDTs is 82% (range 81–99%), and specificity is 89% (range 88–99%) [35].
Polymerase chain reaction (PCR) is another method in the detection of malaria. This method is more sensitive and more specific than all conventional methods in the detection of malaria. It can detect below one parasite/μL. PCR test confirms the presence of parasitic nucleic acid [23,36]. PCR results are often not available fast enough to be useful in malaria diagnosis in endemic areas. However, this method is most helpful in identifying Plasmodium species after diagnosis by microscopy or RDT test in laboratories that might not have microscopic experts. Additionally, PCR is useful for the monitoring of patients receiving antimalaria treatment [36,37].
Indirect methods are used to demonstrate antibodies to malaria-causing agents. Such methods are used in testing people who have been or might be at risk of malaria, such as blood donors and pregnant women. The method is based on an indirect immunofluorescence assay (IFA) or an ELISA test. The IFA is specific and sensitive but not suitable for a large number of samples, and the results are subjective evaluations. For serological testing, ELISA tests are more commonly used [26].
Rapid and accurate diagnosis of malaria is an integral part of appropriate treatment for the affected person and the prevention of the further spread of the infection in the community.
Malaria Treatment through History
Already in the 2nd century BC, a sweet sagewort plant named Qinghai (Latin Artemisia annua) was used for the treatment of malaria in China [38]. Much later, in the 16th century, the Spanish invaders in Peru took over the cinchona medication against malaria obtained from the bark of the Cinchona tree (Latin Cinchona succirubra). From this plant in 1820 the French chemists, Pierre Joseph Pelletier, and Joseph Bienaimé Caventou isolated the active ingredient quinine, which had been used for many years in the chemoprophylaxis and treatment of malaria. In 1970, a group of Chinese scientists led by Dr. Youyou Tu isolated the active substance artemisinin from the plant Artemisia annua, an antimalarial that has proved to be very useful in treating malaria. For that discovery, Youyou Tu received the Nobel Prize for Physiology and Medicine in 2015 [39,40,41]. Most of the artemisinin-related drugs used today are prodrugs, which are activated by hydrolysis to the metabolite dihydroartemisinin. Artemisinin drugs exhibit its antimalarial activity by forming the radical via a peroxide linkage [42]. WHO recommends the use of artemisinin-based combination therapies (ACT) to ensure a high cure rate of P. falciparum malaria and reduce the spread of drug resistance. ACT therapies are used due to high resistance to chloroquine, sulfadoxine-pyrimethamine, and amodiaquine [1]. Due to the unique structure of artemisinins, there is much space for further research. Extensive efforts are devoted to clarification of drug targets and mechanisms of action, the improvement of pharmacokinetic properties, and identifying a new generation of artemisinins against resistant Plasmodium strains [42].
The German chemist Othmer Zeidler synthesized dichlorodiphenyltrichloroethane (DDT) in 1874 during his Ph.D. At that time, no uses of DDT was found, and it just became a useless chemical [43]. The insecticide property of DDT was discovered in 1939 by Paul Müller in Switzerland. DDT began to be used to control malaria at the end of the Second World War [40]. During the Second World War, the success of DDT quickly led to the introduction of other chlorinated hydrocarbons which were used in large amounts for the control of diseases transmitted by mosquito [43]. From the late Middle Ages until 1940, when DDT began to be applied, two-thirds of the world's population had been exposed to malaria, a fact that represented a severe health, demographic, and economic problem [29,40,41,44,45]. DDT is an organochlorine pesticide which was applied in liquid and powder form against the insects. During the Second World War, people were sprayed with DDT. After the war, DDT became a powerful way of fighting malaria by attacking the vector [43].
Five Nobel Prizes associated with malaria were awarded: Youyou Tu in 2015. Ronald Ross received the Nobel Prize in 1902 for the discovery and significance of mosquitoes in the biology of the causative agents in malaria. In 1907, the Nobel was awarded to the already-mentioned Charles Louis Alphonse Laveran for the discovery of the causative agent. Julius Wagner-Jauregg received it in 1927 for the induction of malaria as a pyrotherapy procedure in the treatment of paralytic dementia. In 1947 Paul Müller received it for the synthetic pesticide formula dichlorodiphenyltrichloroethane.
Attempts to produce an effective antimalarial vaccine and its clinical trials are underway. Over the past several decades' numerous efforts have been made to develop effective and affordable preventive antimalaria vaccines. Numerous clinical trials are completed in the past few years. Nowadays are ongoing clinical trials for the development of next-generation malaria vaccines. The main issue is P. vivax vaccine, whose research requires further investigations to identify novel vaccine candidates [46,47,48]. Despite decades of research in vaccine development, an effective antimalaria vaccine has not yet been developed (i.e., with efficacy higher than 50%) [49,50,51]. The European Union Clinical Trials Register currently displays 48 clinical trials with a EudraCT protocol for malaria, of which 13 are still ongoing clinical trials [52]. The malaria parasite is a complex organism with a complex life cycle which can avoid the immune system, making it very difficult to create a vaccine. During the different stages of the Plasmodium life cycle, it undergoes morphological changes and exhibits antigenic variations. Plasmodium proteins are highly polymorphic, and its functions are redundant. Also, the development of malaria disease depends on the Plasmodium species. That way, a combination of different adjuvants type into antigen-specific formulations would achieve a higher efficacy [53,54]. Drugs that underwent clinical trials proved to be mostly ineffective [5,7,55]. However, many scientists around the world are working on the development of an effective vaccine [56,57,58]. Since other methods of suppressing malaria, including medication, insecticides, and bed nets treated with pesticides, have failed to eradicate the disease, and the search for a vaccine is considered to be one of the most important research projects in public health by World Health Organization (WHO).
The best way to fight malaria is to prevent insect bites. Malaria therapy is administered using antimalarial drugs that have evolved from quinine. According to its primary effect, malarial vaccines are divided into pre-erythrocytic (sporozoite and liver-stage), blood-stage, and transmission-blocking vaccines [9,54]. Most medications used in the treatment are active against parasitic forms in the blood (the type that causes disease) (Table 2) [59]. The two crucial antimalarial medications currently used are derived from plants whose medical importance has been known for centuries: artemisinin from the plant Qinghao (Artemisia annua L, China, 4th century) and quinine from Cinchona (South America, 17th century). Side-by-side with artemisinin, quinine is one of the most effective antimalarial drugs available today [13,39,40]. Doxycycline is indicated for malaria chemoprophylaxis for travel in endemic areas. It is also used in combination with the quinine or artesunate for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. The disadvantage of doxycycline is that children and pregnant women cannot use it [29]. Due to the global resistance of P. falciparum to chloroquine, ACTs are recommended for the treatment of malaria, except in the first trimester of pregnancy. ACTs consist of a combination of an artemisinin derivative that fast decreases parasitemia and a partner drug that eliminates remaining parasites over a more extended period. The most common ACTs in use are artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, artesunate-mefloquine, and artesunate with sulfadoxine-pyrimethamine. The ACTs were very efficient against all P. falciparum until recently when numbers of treatment failures raised in parts of Southeast Asia. Atovaquone-proguanil is an option non-artemisinin-based treatment that is helpful for individual cases which have failed therapy with usual ACTs. Although, it is not approved for comprehensive implementation in endemic countries because of the ability for the rapid development of atovaquone resistance. Quinine remains efficient, although it needs a long course of treatment, is poorly tolerated, especially by children, and must be combined with another drug, such as doxycycline or clindamycin. Uncomplicated vivax, malariae, and ovale malaria are handled with chloroquine except in case of chloroquine-resistant P. vivax when an ACT is used [7,29,60,61,62].
Table 2. Overview of the most commonly used antimalarials.
Medication Name
Year of Discovery/Synthesis
Quinine 1600 Cinchona tree, South America Resistance to chloroquine, prophylaxis, and treatment of malaria Inhibition of DNA and RNA synthesis Headache, abortion, or congenital malformations if taken during pregnancy Toxic, less effective than other medication
Chloroquine 1934 Synthesized by German scientist Hans Andersag A most powerful remedy for the prophylaxis and treatment of malaria Inhibition of DNA and RNA synthesis Gastrointestinal disturbances, headache, skin irritation Developed resistance of most strains of P. falciparum to the medication
Primaquine 1953 The 8-aminoquinoline derivative Infections with P. vivax and P. ovale, prophylaxis and treatment of malaria Interferes in transport chain of electrons and destroys parasite mitochondria Anorexia, nausea, anemia, headaches, contraindicated in pregnancy and children under 4 years of age Prevent relapse in P. vivax and P. ovale infection
Doxycycline 1960 Pfizer Inc. New York Prophylaxis in areas with chloroquine resistance and against mefloquine-resistant P. falciparum Inhibition of protein synthesis by binding to 30S ribosomal subunit Gastrointestinal disorders, nausea, vomiting, photosensitivity Effective and cheap, use for treatment and prophylaxis in all malarious areas
Mefloquine 1971 USA army and WHO Multiresistant P. falciparum strains, prophylaxis, and treatment of malaria Damage to parasite membrane Gastrointestinal disorders, CNS disorder, contraindicated in pregnancy and patients with epilepsy Partial resistance, brain damage
Proguanil (chloroguanide) 1953 Biguanide derivate Prophylaxis in infections with P. falciparum Inhibition of DNA synthesis Digestive problems only in large doses The least toxic antimalarial drug
Pyrimethamine 1953 Pyrimidine derivatives For tissue parasites, prophylaxis, and treatment of malaria Folic acid antagonist Gastrointestinal disorders, neuropathy, in high doses also megaloblastic anemia The rapid development of resistance
Atovaquone/proguanil 2000 Ubiquinone analog For the prophylaxis and treatment of malaria Inhibition of cytochrome bc1 in Plasmodium Nausea, vomiting, diarrhea, headache, dizziness, anxiety, difficulty falling asleep, rash, fever Most commonly used, fewer side effects and more expensive than mefloquine, P. falciparum resistance
CNS—central nervous system.
Malaria in Europe
In Europe, malaria outbreaks occurred in the Roman Empire [63,64] and the 17th century. Up until the 17th century it was treated as any fever that people of the time encountered. The methods applied were not sufficient and included the release of blood, starvation, and body cleansing. As the first effective antimalarial drug, the medicinal bark of the Cinchona tree containing quinine was mentioned and was initially used by the Peruvian population [14]. It is believed that in the fourth decade of the 17th century it was transferred to Europe through the Spanish Jesuit missionaries who spread the treatment to Europe [65].
Contemporary knowledge of malaria treatment is the result of the work of a few researchers. Some of the researchers are Alphonse Laveran, Ronald Ross, and Giovanni Battista Grassi. In November 1880, Laveran, who worked as a military doctor in Algeria, discovered the causative agents of malaria in the blood of mosquitoes and found that it was a kind of protozoa [66]. Laveran noticed that protozoa could, just like bacteria, live a parasitic way of life within humans and thus cause disease [66]. Nearly two decades later, more precisely in 1898, Ronald Ross, a military doctor in India, discovered the transmission of bird malaria in the saliva of infected mosquitos, while the Italian physician Giovanni Battista Grassi proved that malaria was transmitted from mosquitoes to humans, in the same year. He also proved that not all mosquitoes transmit malaria, but only a specific species (Anopheles) [17]. This discovery paved the way for further research.
The global battle against malaria started in 1955, and the program was based on the elimination of mosquitoes using DDT and included malarial areas of the United States, Southern Europe, the Caribbean, South Asia, but only three African countries (South Africa, Zimbabwe, and Swaziland). In 1975, the WHO announced that malaria had been eradicated in Europe and all recorded cases were introduced through migration [67,68].
Malaria in Croatia
In Croatia, the first written document that testifies to the prevention of malaria is the Statute of the town of Korčula from 1265. In 1874, the Law on Health Care of Croatia and Slavonia established the public health service that was directed towards treating malaria. There was no awareness nor proper medical knowledge about malaria, but the drainage was carried out to bring the 'healthy air' in the cities [69,70]. In 1798 physician Giuseppe Arduino notified the Austrian government about malaria in Istria. A government representative Vincenzo Benini accepted a proposed sanitary measure of the drainage of wetlands [71]. In 1864, the drainage of wetlands around Pula and on the coastal islands began, and since 1902 a program for the suppression of malaria by treatment of patients using quinine has been applied [72]. In 1922, the Institute for Malaria was founded in Trogir. In 1923, on the island of Krk, a project was started to eradicate malaria by the sanitation of water surfaces and the treatment of the patients with quinine, led by Dr. Otmar Trausmiller [66]. Since 1924, besides chemical treatment, biological control of mosquitoes has been established by introducing the fish Gambusia holbrooki to Istria and the coast [73]. In 1930 legislation was passed to enforce village sanitation, which included the construction of water infrastructure and safe wells, contributing to the prevention of malaria. Regular mosquito fogging with arsenic green (copper acetoarsenite) was introduced, and larvicidal disinfection of stagnant water was carried out.
Since malaria occurs near swamps, streams, ravines, and places where mosquitoes live near water, this disease has been present throughout history in Croatia, and it has often become an epidemic [74]. It was widespread in the area of Dalmatia, the Croatian Littoral region, Istria, and river flows. In the area of the Croatian Littoral, it was widespread on some islands, such as Krk, Rab, and Pag, while the mainland was left mainly clear of it [75]. The ethnographer Alberto Fortis (1741–1803) who traveled to Dalmatia, noted impressions recording details of malaria that was a problem in the Neretva River valley. Fortis wanted to visit that area, but the sailors on the ship were afraid, probably because they were afraid to go to a place where there had been a disease outbreak known as the Neretva plague [76]. This Neretva plague was, in fact, malaria, and it is believed that due to it, the Neretva was nicknamed "Neretva—damned by God" [77,78]. Speaking of the Neretva region, Fortis states that the number of mosquitoes in that wetland area was so high that people had to sleep in stuffy canopy tents to defend themselves. Fortis also states that there were so many mosquitoes that he was affected by it. During the stay, Fortis met a priest who had a bump on the head claiming it had occurred after a mosquito bite and believed that the fever that infected the people of the Neretva Valley was also a consequence of the insect bites there [76]. In a manuscript, Dugački described some of the epidemics in Croatia. Thus, noted the small population of Nin in 1348, which was the result of the unhealthy air and high mortality of the population. Three centuries later, in 1646, the fever was mentioned in Novigrad, while the year 1717 was crucial for to the Istrian town of Dvigrad, which was utterly deserted due to malaria. At the beginning of the 20th century, more precisely in 1902, the daily press reported that the Provincial Hospital in Zadar was full of people affected by malaria. The extent to which this illness was widespread is proved by the fact that at the beginning of the 20th century about 180,000 people suffered from it in Dalmatia [18]. The volume and frequency of epidemics in Dalmatia resulted in the arrival of the Italian malariologist Grassi and the German parasitologist Schaudin. The procedures of quininization began to be applied, and in 1908 25 physicians and 423 pill distributors were to visit the villages and divide pills that had to be taken regularly to the people to eradicate malaria [75].
Likewise, in Slavonia, malaria had also a noticeable effect, and it was widespread in the 18th century due to a large number of swamps that covered the region. Such areas were extremely devastating for settlers who were more vulnerable to the disease than its domestic population [79]. Friedrich Wilhelm von Taube (1728–1778) recorded the disease and stated that the immigrant Germans were primarily affected by malaria and that the cities of Osijek and Petrovaradin can be nicknamed "German Cemeteries" [80]. According to Skenderović, the high mortality of German settlers from malaria was not limited only to the Slavonia region but also to the Danubian regions in which the Germans had settled in the 18th century, with Banat and Bačka [79] having the most significant number of malaria cases. The perception of Slavonia in the 18th century was not a positive one. Even Taube stated that Slavonia was not in good standing in the Habsburg Monarchy and that the nobility avoided living there. As some of the reasons for this avoidance, Taube mentioned the unhealthy air and the many swamps in the area around in which there was a multitude of insects. Taube noted that mosquitoes appear to be larger than in Germany and that its bite was much more painful. A change in the situation could only be brought about by drying the swamp, in his opinion [80]. Since malaria had led to the death of a large number of people, the solution had to be found to stop its further spread. Swamp drying was finally accepted by the Habsburg Monarchy and some European countries as a practical solution and, thus, its drainage began during the 18th century, resulting in cultivated fields [79].
Since epidemics of malaria continued to occur, there is one more significant record of the disease in the Medical Journal of 1877. In it, the physician A. Holzer cites his experiences from Lipik and Daruvar where he had been a spa physician for a long time. Holzer warns of the painful illness noticed at spa visitors suffering from the most in July and August. As a physician, Holzer could not remain indifferent to the fact that he did not see anyone looking healthy. It also pointed out that other parts of Croatia were not an exception. As an example, Holzer noted Virovitica County, where malaria was also widespread. He wanted to prevent the development and spread of the illness. Believing that preventing the toxic substances from rising into the air would stop the disease, the solution was to use charcoal that has the properties of absorbing various gases and, thus, prevents vapor rising from the ground [81].
Dr. Andrija Štampar (1888–1958) holds a prominent place in preventing the spread of malaria. Štampar founded the Department of Malaria, and numerous antimalaria stations, hygiene institutes, and homes of national health. Dr. Štampar devoted his life to educating the broader population about healthy habits and, thus, prevents the spread of infectious diseases. Many films were shown, including a film entitled 'Malaria of Trogir' in Osijek in 1927, with numerous health lectures on malaria [82]. After the end of the Second World War, a proposal for malaria eradication measures was drafted by Dr. Branko Richter. These measures, thanks to Dr. Andrija Štampar, are being used in many malaria-burdened countries. For the eradication of malaria in Croatia and throughout Yugoslavia, DDT has been used since 1947 [83].
Malaria is still one of the most infectious diseases that cause far more deaths than all parasitic diseases together. Malaria was eradicated in Europe in 1975. After that year, malaria cases in Europe are linked to travel and immigrants coming from endemic areas. Although the potential for malaria spreading in Europe is very low, especially in its western and northern parts, it is still necessary to raise awareness of this disease and keep public health at a high level in order to prevent the possibility of transmitting the disease to the most vulnerable parts of Europe [84].
Unofficial data show that malaria disappeared from Croatia in 1958, while the World Health Organization cites 1964 as the year when malaria was officially eradicated in Croatia [45,75]. Nonetheless, some cases of imported malaria have been reported in Croatia since 1964. The imported malaria is evident concerning Croatia's orientation to maritime affairs, tourism, and business trips. Namely, malaria is introduced to Croatia by foreign and domestic sailors, and in rare cases by tourists, mainly from the countries of Africa and Asia [75,85]. According to the reports of the Croatian Institute of Public Health, since the eradication of this disease 423 malaria cases have been reported, all imported [86]. Figure 1 shows the number of imported malaria cases in Croatia from 1987–2017, and Figure 2 the causative Plasmodium species of those cases (Figure 1 and Figure 2) [86,87].
Figure 1. Imported malaria cases in Croatia from 1987–2017.
Figure 2. The causative agents of imported malaria in Croatia.
There is also massive and uncontrollable migration from Africa and Asia (mostly due to climate change) of both humans and birds, from countries with confirmed epidemics. This issue is an insurmountable problem if measured by the traditional approach. Insecticides (DDT, malathion, etc.) synthetic pyrethroids, in addition to inefficiency, impact the environment (harm bees, fruits, vines, etc.). Consequently, scientists have patiently established a mosquito control strategy (University of Grenoble, Montpellier) which includes a meticulous solution to the mosquito vector effect (malaria, arbovirus infection, West Nile virus) by changes in agriculture, urbanism, public services hygiene [88].
Northeastern Slavonia is committed to applying methods that are consistent with such achievements, with varying success, as certain limitations apply to protected natural habitats (Kopački rit) [89].
There is a historical link between population movement and global public health. Due to its unique geostrategic position, in the past, Croatia has been the first to experience epidemics that came to Europe through land and sea routes from the east. Adriatic ports and international airports are still a potential entry for the import of individual cases of communicable diseases. Over the past few years, sailors, as well as soldiers who worked in countries with endemic malaria, played a significant role in importing malaria into Croatia. Successful malaria eradication has been carried out in Croatia. Despite that in Croatia are still many types of Anopheles, which means that the conditions of transmission of the imported malaria from the endemic areas still exist. The risk of malaria recrudesce is determined by the presence of the vector, but also by the number of infected people in the area. Due to climate change, it is necessary to monitor the vectors and people at risk of malaria. Naturally- and artificially-created catastrophes, such as wars and mass people migration from endemic areas, could favor recrudescing of malaria. Once achieved, eradication would be maintained if the vector capacities are low and prevention measures are implemented. The increased number of malaria cases worldwide, the recrudesce of indigenous malaria cases in the countries where the disease has been eradicated, the existence of mosquitoes that transmit malaria and the number of imported malaria cases in Croatia are alarming facts. Health surveillance, including obligatory and appropriate prophylaxis for travelers to endemic areas, remains a necessary public health care measure pointed at managing malaria in Croatia.
Malaria Trends in the World
The WHO report on malaria in 2017 shows that it is difficult to achieve two crucial goals of a Global Technical Strategy for Malaria. These are a reduction in mortality and morbidity by at least 40% by 2020. Since 2010, there has been a significant reduction in the burden of malaria, but analysis suggests a slowdown and even an increase in the number of cases between 2015 and 2017. Thus, the number of malaria cases in 2017 has risen to 219 million, compared to 214 million cases in 2015 and 239 million cases in 2010. Figure 3 presents the reported number of malaria cases per WHO region from 1990–2017 [1,90]. The most critical step in the global eradication of malaria is to reduce the number of cases in countries with the highest burden (many in Africa). The number of deaths from disease is declining, thus, in 2017 there were 435,000 deaths from malaria globally, compared with 451,000 in 2016, and 607,000 deaths in 2010. Figure 4 presents the number of malaria deaths from 1990-2017 [1,90]. Despite the delay in global progress, there are countries with decreasing malaria cases during 2017. Thus, India in 2017, compared with 2016, recorded a 24% decline of malaria cases. The number of countries reporting less than 10,000 malaria cases is growing, from 37 countries in 2010, to 44 in 2016, and to 46 in 2017. Furthermore, the number of countries with fewer than 100 indigenous malaria cases growing from 15 in 2010, to 26 countries in 2017 [1].
Figure 3. Reported malaria cases per WHO region from 1990–2017.
Figure 4. Reported malaria deaths per WHO region from 1990–2017.
Funding in malaria has not changed much. During 2017, US$3.1 billion was invested in malaria control and elimination globally. That was 47% of the expected amount by 2020. The USA was the largest single international donor for malaria in 2017 [1,91].
The most common global method of preventing malaria is insecticide-treated bed nets (ITNs). The WHO report on insecticide resistance showed that mosquitoes became resistant to the four most frequently used classes of insecticides (pyrethroids, organochlorines, carbamates, and organophosphates), which are widespread in all malaria-endemic countries [1,7,92].
Drug resistance is a severe global problem, but the immediate threat is low, and ACT remains an effective therapy in most malaria-endemic countries [1,93].
According to the WHO, Africa still has the highest burden of malaria cases, with 200 million cases (92%) in 2017, then Southeast Asia (5%), and the Eastern Mediterranean region (2%). The WHO Global Technical Strategy for Malaria by 2020 is the eradication of malaria from at least ten countries that were malaria-endemic in 2015 [1].
The march towards malaria eradication is uneven. Indigenous cases in Europe, Central Asia, and some countries in Latin America are now sporadic. However, in many sub-Saharan African countries, elimination of malaria is more complicated, and there are indications that progress in this direction has delayed. Elimination of vivax and human knowlesi malaria infections are another challenge [7].
World Health Organization. World Malaria Report 2018; WHO: Geneva, Switzerland,
White, N.J.N.; Pukrittayakamee, S.; Hien, T.T.T.; Faiz, M.A.; Mokuolu, O.A.O.; Dondorp, A.A.M. Malaria. Lancet 2014, 383, 723–735, doi:10.1016/S0140-6736(13)60024-0.
Pan American Health Organization; World Health Organization. Epidemiological Alert, Increase of Malaria in the Americas; PAHO: Washington, DC, USA, 2018.
Dhiman, S. Are malaria elimination efforts on right track? An analysis of gains achieved and challenges ahead. Dis. Poverty 2019, 8, 14, doi:10.1186/s40249-019-0524-x.
Walker, N.; Nadjm, B.; Whitty, C. Malaria. Medicine 2017, 42, 52–58, doi:10.1016/j.mpmed.2013.11.011.
Antinori, S.; Galimberti, L.; Milazzo, L.; Corbellino, M. Biology of human malaria plasmodia including Plasmodium knowlesi. J. Hematol. Infect. Dis. 2012, 4, e2012013, doi:10.4084/MJHID.2012.013.
Ashley, E.A.; Pyae Phyo, A.; Woodrow, C.J. Malaria. Lancet 2018, 391, 1608–1621, doi:10.1016/S0140-6736(18)30324-6.
Singh, B.; Daneshvar, C. Human Infections and Detection of Plasmodium knowlesi. Microbiol. Rev. 2013, 26, 165–184, doi:10.1128/CMR.00079-12.
Vuk, I.; Rajic, Z.; Zorc, B. Malaria and antimalarial drugs. Farm Glas 2008, 64, 51–60.
Soulard, V.; Bosson-Vanga, H.; Lorthiois, A.; Roucher, C.; Franetich, J.-F.; Zanghi, G.; Bordessoulles, M.; Tefit, M.; Thellier, M.; Morosan, S.; et al. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice. Commun. 2015, 6, 7690, doi:10.1038/ncomms8690.
Josling, G.A.; Llinás, M. Sexual development in Plasmodium parasites: Knowing when it's time to commit. Rev. Genet. 2015, 13, 573–587, doi:10.1038/nrmicro3519.
Blut, A. Untergruppe "Bewertung Blutassoziierter Krankheitserreger." Transfus. Med. Hemother. 2009, 36, 48–60, doi:10.1159/000197327.
Cowman, A.; Healer, J.; Marapana, D.; Marsh, K. Malaria, Biology and Disease. Cell 2016, 167, 610–624, doi:10.1016/j.cell.2016.07.055.
Cartwright, F.; Biddis, M. Disease and History; Naklada Ljevak: Zagreb, Croatia, 2006.
Lehrer, S. Vitezi Medicine; Prosveta: Beograd, Serbia, 1981.
Moss, W.; Shah, S.; Morrow, R. The History of Malaria and its Control. Encycl. Public Health 2008, 389–398, doi:10.1016/B978-012373960-5.00374-9.
Dugacki, V. Dr. Rudolf Battara operation in Nin in 1902, the first systematic battle attempt against malaria in Croatia. Jaderina 2005, 35, 33–40.
Jovic, S. Istorija Medicine i Zdravstvene Kulture na tlu Dansnje Vojvodine 1718–1849 II; dio. Matica srpska, Srpska akademija nauka i umetnosti: Novi Sad, Serbia, 1998.
Tan, S.Y.; Ahana, A. Charles Laveran (1845–1922), Nobel laureate pioneer of malaria. Med. J. 2009, 50, 657–658.
Saifi, M.A.; Wajihullah, Siddiqui, M.I.; Al-Khalifa, M.S.; Malaria: Patterns of relapse and resistance. King Saud Univ. Sci. 2010, 22, 31–36, doi:10.1016/J.JKSUS.2009.12.005.
Chu, C.S.; White, N.J. Management of relapsing Plasmodium vivax malaria. Expert Rev. Anti-Infect. Ther. 2016, 14, 885, doi:10.1080/14787210.2016.1220304.
Murphy, S.C.; Shott, J.P.; Parikh, S.; Etter, P.; Prescott, W.R.; Stewart, V.A. Malaria diagnostics in clinical trials. J. Trop. Med. Hyg. 2013, 89, 824–839, doi:10.4269/ajtmh.12-0675.
Tangpukdee, N.; Duangdee, C.; Wilairatana, P.; Krudsood, S. Malaria diagnosis, a brief review. Korean J. Parasitol. 2009, 47, 93–102, doi:10.3347/kjp.2009.47.2.93.
Trampuz, A.; Jereb, M.; Muzlovic, I.; Prabhu, R.M. Clinical review, Severe malaria. Care 2003, 7, 315–323, doi:10.1186/cc2183.
She, R.C.; Rawlins, M.L.; Mohl, R.; Perkins, S.L.; Hill, H.R.; Litwin, C.M. Comparison of Immunofluorescence Antibody Testing and Two Enzyme Immunoassays in the Serologic Diagnosis of Malaria. Travel Med. 2007, 14, 105–111, doi:10.1111/j.1708-8305.2006.00087.x.
Oh, J.S.; Kim, J.S.; Lee, C.H.; Nam, D.H.; Kim, S.H.; Park, D.W.; Lee, C.K.; Lim, C.S.; Park, G.H. Evaluation of a malaria antibody enzyme immunoassay for use in blood screening. Inst. Oswaldo Cruz 2008, 103, 75–78, doi:10.1590/S0074-02762008005000008.
Kakkilaya, B. Rapid Diagnosis of Malaria. Med. 2003, 34, 602–608, doi:10.1309/J4ANKCCJ147JB2FR.
Abba, K.; Kirkham, A.J.; Olliaro, P.L.; Deeks, J.J.; Donegan, S.; Garner, P.; Takwoingi, Y. Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries. Cochrane Database Syst. Rev. 2014, 12, doi:10.1002/14651858.CD011431.
World Health Organization. Guidelines for the Treatment of Malaria, 3rd ed.; WHO: Geneva, Switzerland, 2015.
World Health Organization. Malaria Rapid Diagnostic Test Performance, Results of WHO Product Testing of Malaria RDTs, Round 8 (2016–2018); WHO: Geneva, Switzerland, 2018.
Ranadive, N.; Kunene, S.; Darteh, S.; Ntshalintshali, N.; Nhlabathi, N.; Dlamini, N.; Chitundu, S.; Saini, M.; Murphy, M.; Soble, A. Limitations of Rapid Diagnostic Testing in Patients with Suspected Malaria, A Diagnostic Accuracy Evaluation from Swaziland, a Low-Endemicity Country Aiming for Malaria Elimination. Infect. Dis. 2017, 64, 1221, doi:10.1093/CID/CIX131.
Berhane, A.; Russom, M.; Bahta, I.; Hagos, F.; Ghirmai, M.; Uqubay, S. Rapid diagnostic tests failing to detect Plasmodium falciparum infections in Eritrea, an investigation of reported false negative RDT results. J. 2017, 16, 105, doi:10.1186/s12936-017-1752-9.
Kozycki, C.T.; Umulisa, N.; Rulisa, S.; Mwikarago, E.I.; Musabyimana, J.P.; Habimana, J.P.; Karema, C.; Krogstad, D.J. False-negative malaria rapid diagnostic tests in Rwanda: Impact of Plasmodium falciparum isolates lacking hrp2 and declining malaria transmission. J. 2017, 16, 123, doi:10.1186/s12936-017-1768-1.
World Health Organization. False-negative RDT results and implications of new reports of P. falciparum histidine-rich protein 2/3 gene deletions. WHO 2017, doi:10.1186/1475-2875-10-166.
Murray, C.K.; Gasser, R.A.; Magill, A.J.; Miller, R.S. Update on Rapid Diagnostic Testing for Malaria. Microbiol. Rev. 2008, 21, 97–110, doi:10.1128/CMR.00035-07.
Mathison, B.A.; Pritt, B.S. Update on Malaria Diagnostics and Test Utilization. Clin. Microbiol. 2017, 55, 2009–2017, doi:10.1128/JCM.02562-16.
Rougemont, M.; Van Saanen, M.; Sahli, R.; Hinrikson, H.P.; Bille, J.; Jaton, K. Detection of Four Plasmodium Species in Blood from Humans by 18S rRNA Gene Subunit-Based and Species-Specific Real-Time PCR Assays. Clin. Microbiol. 2004, 42, 5636–5643, doi:10.1128/JCM.42.12.5636-5643.2004.
Hsu, E. The history of qing hao in the Chinese materia medica. R. Soc. Trop. Med. Hyg. 2006, 100, 505–508, doi:10.1016/j.trstmh.2005.09.020.
Achan, J.; O Talisuna, A.; Erhart, A.; Yeka, A.; Tibenderana, J.K.; Baliraine, F.N.; Rosenthal, P.J.; D'Alessandro, U. Quinine, an old anti-malarial drug in a modern world: Role in the treatment of malaria. J. 2011, 10, 144.
Meshnick, S.R.; Dobson, M.J. The History of Antimalarial Drugs. In Antimalarial Chemotherapy, Mechanisms of Action, Resistance, and New Directions in Drug Discovery; Rosenthal, P., Ed.; Humana Press: Totowa NJ, USA, 2001; p. 396.
World Health Organization. Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation; WHO: Geneva, Switzerland, 2001.
Guo, Z. Artemisinin anti-malarial drugs in China. Acta Pharm. Sin. B 2016, 6, 115–124, doi:10.1016/j.apsb.2016.01.008.
Ray, D. Organochlorine and Pyrethroid Insecticides. Toxicol. 2010, 13, 445–457, doi:10.1016/B978-0-08-046884-6.01327-0.
Flannery, E.L.; Chatterjee, A.K.; Winzeler, E.A. Antimalarial drug discovery—Approaches and progress towards new medicines. Rev. Microbiol. 2013, 11, 849–862, doi:10.1038/nrmicro3138.
Zhao, X.; Smith, D.L.; Tatem, A.J. Exploring the spatiotemporal drivers of malaria elimination in Europe. J. 2016, 15, 122, doi:10.1186/s12936-016-1175-z.
Karunamoorthi, K. Malaria vaccine, a future hope to curtail the global malaria burden. J. Prev. Med. 2014, 5, 529–538.
Moreno, A.; Joyner, C. Malaria vaccine clinical trials, what's on the horizon. Opin. Immunol. 2015, 35, 98–106, doi:10.1016/j.coi.2015.06.008.
Coelho, C.H.; Doritchamou, J.Y.A.; Zaidi, I.; Duffy, P.E. Advances in malaria vaccine development, report from the 2017 malaria vaccine symposium. NPJ Vaccines 2017, 2, 34, doi:10.1038/s41541-017-0035-3.
Mahmoudi, S.; Keshavarz, H. Efficacy of phase 3 trial of RTS, S/AS01 malaria vaccine, The need for an alternative development plan. Vaccines Immunother. 2017, 13, 2098–2101, doi:10.1080/21645515.2017.1295906.
Rénia, L.; Goh, Y.S.; Peng,. K, Mauduit, M.; Snounou, G. Assessing Malaria Vaccine Efficacy. In Towards Malaria Elimination: A Leap Forw; Manguin, S., Dev, V., Eds.; IntechOpen: London, UK, 2018; pp. 339–362, doi:10.5772/intechopen.77044.
Draper, S.J.; Sack, B.K.; King, C.R.; Nielsen, C.M.; Rayner, J.C.; Higgins, M.K.; et al. Malaria Vaccines, Recent Advances and New Horizons. Cell Host Microbe 2018, 24, 43–56, doi:10.1016/j.chom.2018.06.008.
Clinical Trials Register—Clinical Trials for Malaria 2019. Available online: https://www.clinicaltrialsregister.eu/ctr-search/search?query=Malaria (accessed on 30 April 2019).
Crompton, P.D.; Pierce, S.K.; Miller, L.H. Advances and challenges in malaria vaccine development. Clin. Investig. 2010, 120, 4168–4178, doi:10.1172/JCI44423.
Arama, C.; Troye-Blomberg, M. The path of malaria vaccine development, challenges and perspectives. Intern. Med. 2014, 275, 456–466, doi:10.1111/joim.12223.
Kisalu, N.K.; Idris, A.H.; Weidle, C.; Flores-Garcia, Y.; Flynn, B.J.; Sack, B.K.; Murphy, S.; Schön, A.; Freire, E.; Francica, J.R.; et al. A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Med. 2018, 24, 408–416, doi:10.1038/nm.4512.
Claudia, F. Malaria vaccine–is it still required? Are vaccine alternatives enough to achieve malaria control? Asian Pac. J. Trop. Biomed. 2014, 4, S541–S544, doi:10.12980/APJTB.4.2014APJTB-2014-0181.
Greenwood, B.; Targett, G. Malaria vaccines and the new malaria agenda. Microbiol. Infect. 2011, 17, 1600–1607, doi:10.1111/j.1469-0691.2011.03612.x.
Hoffman, S.L.; Vekemans, J.; Richie, T.; Duffy, P. The March Toward Malaria Vaccines. J. Prev. Med. 2015, 49, S319–S333, doi:10.1016/j.amepre.2015.09.011.
Shingadia, D. Treating malaria in the UK. Child Health 2014, 24, 232–235, doi:10.1016/j.paed.2013.10.003.
Kremsner, P.G.; Krishna, S. Antimalarial combinations. Lancet 2004, 364, 285–294, doi:10.1016/S0140-6736(04)16680-4.
Price, R.N.; Douglas NM. Artemisinin combination therapy for malaria, beyond good efficacy. Infect. Dis. 2009, 49, 1638–1640, doi:10.1086/647947.
Nabudere, H.; Upunda, G.L.; Juma, M. Policy brief on improving access to artemisinin-based combination therapies for malaria in the East African community. J. Technol. Assess Health Care 2010, 26, 255–259, doi:10.1017/S026646231000019X.
Sallares, R. Malaria and Rome: A History of Malaria in Ancient Italy; Oxford University Press: Oxford, UK, 2002; doi:10.1093/acprof,oso/9780199248506.001.0001.
Micallef, M.J. The Roman fever, observations on the understanding of malaria in the ancient Roman world. J. Aust. 2016, 205, 501–503, doi:10.5694/mja16.00206.
Jugoslavenski Leksikografski Zavod. Medical Encycolpedia; Jugoslavenski Leksikografski Zavod: Zagreb, Yugoslavia, 1969; p. 374.
Trausmiller, O. Malarija i civilizacija. Priroda 1936, 3, 76–83.
Odolin, S.; Gautret, P.; Parola, P. Epidemiology of imported malaria in the mediterranean region. J. Hematol. Infect. Dis. 2012, 4, e2012031.
World Health Organization. Fact Sheet—History of Malaria Elimination in the European Region; WHO: Geneva, Switzerland, 2016.
Mlinaric, D. Eco-historical area of the istrian borderland as a framework of the development of endemic diseases. Istar. Arh. 2010, 17, 155–177.
Radosevic, M. Health conditions in the municipality of Medulin through history. In Municipality of Medulin Monograph; Bader, A., Ed.; Opcina Medulin: Medulin, Croatia, 2013; pp. 314–325.
Rudetic, I. Malaria. In Istarska Enciklopedija; Bertosa, M., Matijasic, R., Eds.; Leksikografski Zavod Miroslav Krleza: Zagreb, Croatia, 2005; p. 544.
Bakic, J. Seven centuries of the prevention of spreading of the infectious diseases into Croatia—Overview of the 60th anniversary of establishment of modern pest control in Croatia. Cas. Zavod Javno Zdr. 2011, 7, 1–17.
Bakic, J. Trust worthy facts on first medically-entomological laboratory and introduction of Gambusia holbrooki into Croatia. Cas. Zavod Javno Zdr. 2006, 2, 20–25.
Nezic, E. Ribica gambuzija u borbi protiv malarije. J. Fish. 1938, 1, 62–66.
Mulic, R.; Aljinovic, L.; Gizdic, Z.; Petri, N.M. Malaria in Republic of Croatia, past, present and future. Vjesn. 2000, 122, 51–55.
Fortis, A. Put Po Dalmaciji; Globus: Zagreb, Croatia, 1984.
Wokaunn, M.; Juric, I.; Vrbica, Z. Between stigma and dawn of medicine, the last leprosarium in Croatia. Med. J. 2006, 47, 759–766.
Tomasic, P. Malarija i blagostanje čovjeka. Priroda 1947, 4, 126–130.
Skenderovic, R. Health Reforms Introduced by Maria Theresa in Provincial Slavonia and Generale Normativum Sanitatis of 1770. Slavon. 2005, 5, 115–143.
Von Taube, F.W. Slavonija i Srijem 1777./1778; Drzavni Arhiv u Osijeku: Osijek, Croatia, 2012.
Holzer, A. Asaniranje domacih predjela malarije. Liecnicki Viest. 1877, 4, 56–59.
Majcen, V. The film funds of the school of national health (Andrija Stampar) at the Croatian film-library within the Croatian archive. Vjesn. 1987, 30, 71–88.
Miletic-Medved, M.; Bozikov, J.; Uzarević, Z. Branko Cvjetanovic i Branimir Richter—Suradnici Andrije Stampara. Zavoda Za Znan. Umjetnicki Rad Osijeku 2012, 28, 103–113.
Piperaki, E.T.; Daikos, G.L. Malaria in Europe, emerging threat or minor nuisance? Microbiol. Infect. 2016, 22, 487–493, doi:10.1016/J.CMI.2016.04.023.
Mulic, R. Malaria in Croatia, from eradication until today. J. 2012, 11, P135, doi:10.1186/1475-2875-11-S1-P135.
Peric, D. Skrobonja, I.; Skrobonja, A.; Peric, D.; Skrobonja, I.; Skrobonja, A. Malaria in Croatia in the period between 1987 to 2006. Vjesn. 2009, 131, 192–195.
Stevanovic, R.; Capak, K.; Brkic, K. Croatian Health Statistics Yearbook 2017; Croatian Institute of Public Health: Zagreb, Croatia, 2018.
Talapko, J. Optimizacija metoda za uništavanje komaraca, ali i zaštite okoline. Vjesn. 1986, 2, 353–356.
Tucak, A.; Dimitrijevic, M.; Gucunski, D.; Konstantinovic, B.; Miljus, B.; Grgic, Z.; Balog, Z.; Paulus, R.; Talapko, J. Multicentricni Program Istraživanja Ekologije Komaraca na Podrucju Sjeveroistocne Slavonije; Sveuciliste u Osijeku, Znanstvena Jedinica za Klinicko-Medicinska Istraživanja Opce bolnice Osijek: Osijek, Croatia, 1985.
World Health Organization. World Malaria Report 2010; WHO: Geneva, Croatia, 2010.
Patouillard, E.; Griffin, J.; Bhatt, S.; Ghani, A.; Cibulskis, R. Global investment targets for malaria control and elimination between 2016 and 2030. BMJ Glob. Health 2017, 2, e000176, doi:10.1136/bmjgh-2016-000176.
World Health Organization. Global Report on Insecticide Resistance in Malaria Vectors, 2010–2016; WHO: Geneva, Croatia, 2018.
Alonso, P.; Noor, A,M. The global fight against malaria is at crossroads. Lancet 2017, 390, 2532–2534, doi:10.1016/S0140-6736(17)33080-5.
Anopheles antimalarials malaria Plasmodium
Ivana, Škrlec. Malaria, Encyclopedia, 2019, v1, Available online: https://encyclopedia.pub/229


A structure in Mellat Park in north Tehran called 'Installation #5' has been selected among the 34 best student design-build projects from around the world in the past year by Archdaily website.
For the third year in a row, Archdaily asked its student readers to submit the design-build projects which they recently worked on. It got hundreds of submissions, its website reported.
'Installation #5' is inhabitable urban furniture placed in the middle of Mellat Park in north Tehran, made of rotating steel sections in space and laced together with a dense web of steel cables that produce original ergonomic shapes.
Beneath the structure lies a concrete and steel foundation that supports the intricate tensile structure.
It is created by CAAT Studio in Tehran which has been involved in architecture and construction from 2010. Architect Mehdi Kamboozia is the executive director of the studio who has worked on the project along with students Helena Qanbari, Behrang Baniadam, Aria Goleh, Shamim Aqazadeh, Ashkan Radnia, Mehran Alinejad and Atieh Aqayi.
ArchDaily is a platform to help architects design a better world. It provides access to critical information to help architects create better works.
It seeks to help improve the quality of life of the billions of people who will presumably converge on cities across continents in the next decades by providing inspiration, knowledge and tools to urban planners and architects who will have to deal with monumental urban challenges in the not too distant future.


text:
Official tax return reveals how one trader nabbed annual gains of 228%, 309% and 339%. His tax return was released online, exposing this simple trading technique used to pocket nearly half a million in profits.
NYSE:CFX - Colfax Stock Price, Forecast & News
Adding Colfax Corp
Colfax Corporation operates as a diversified technology company worldwide. The company operates through Air and Gas Handling, and Fabrication Technology segments. The Air and Gas Handling segment designs, manufactures, installs, and maintains heavy-duty fans, rotary heat exchangers, blowers, and compressors. It markets air and gas handling products under the Howden brand name. Read More…
Industry Pumps & pumping equipment
Sub-IndustryIndustrial Machinery
SectorIndustrial Products
Current SymbolNYSE:CFX
Webhttp://www.colfaxcorp.com/
Price / Cash Flow10.42
Net Margins-12.40%
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Colfax (NYSE:CFX) Frequently Asked Questions
What is Colfax's stock symbol?
Colfax trades on the New York Stock Exchange (NYSE) under the ticker symbol "CFX."
How were Colfax's earnings last quarter?
Colfax Corp (NYSE:CFX) issued its quarterly earnings data on Thursday, October, 31st. The industrial products company reported $0.50 earnings per share (EPS) for the quarter, beating the Thomson Reuters' consensus estimate of $0.46 by $0.04. The industrial products company had revenue of $846.52 million for the quarter, compared to analyst estimates of $852.39 million. Colfax had a negative net margin of 12.40% and a positive return on equity of 9.06%. Colfax's revenue was up 61.5% compared to the same quarter last year. During the same period last year, the company posted $0.22 earnings per share. View Colfax's Earnings History.
When is Colfax's next earnings date?
Colfax is scheduled to release their next quarterly earnings announcement on Wednesday, February 12th 2020. View Earnings Estimates for Colfax.
What guidance has Colfax issued on next quarter's earnings?
Colfax updated its FY 2020 Pre-Market earnings guidance on Wednesday, December, 18th. The company provided EPS guidance of 2.10-2.20 for the period, compared to the Thomson Reuters consensus estimate of $2.22.
What price target have analysts set for CFX?
17 analysts have issued 1 year price targets for Colfax's shares. Their forecasts range from $9.00 to $44.00. On average, they expect Colfax's share price to reach $30.86 in the next twelve months. This suggests that the stock has a possible downside of 18.9%. View Analyst Price Targets for Colfax.
What is the consensus analysts' recommendation for Colfax?
17 Wall Street analysts have issued "buy," "hold," and "sell" ratings for Colfax in the last year. There are currently 4 hold ratings and 13 buy ratings for the stock, resulting in a consensus recommendation of "Buy." View Analyst Ratings for Colfax.
Has Colfax been receiving favorable news coverage?
Media headlines about CFX stock have been trending extremely negative on Monday, according to InfoTrie Sentiment Analysis. InfoTrie scores the sentiment of news coverage by monitoring more than six thousand blog and news sources. The firm ranks coverage of publicly-traded companies on a scale of negative five to positive five, with scores nearest to five being the most favorable. Colfax earned a coverage optimism score of -5.0 on InfoTrie's scale. They also gave news articles about the industrial products company a news buzz of 0.0 out of 10, indicating that recent news coverage is extremely unlikely to have an effect on the stock's share price in the immediate future. View News Stories for Colfax.
Who are some of Colfax's key competitors?
Some companies that are related to Colfax include Illinois Tool Works (ITW), Ingersoll-Rand (IR), Parker-Hannifin (PH), Stanley Black & Decker (SWK), Dover (DOV), Xylem (XYL), IDEX (IEX), Nordson (NDSN), Snap-on (SNA), Graco (GGG), Pentair (PNR), Woodward, Inc.Common Stock (WWD), Gardner Denver (GDI), Donaldson (DCI) and Flowserve (FLS).
What other stocks do shareholders of Colfax own?
Based on aggregate information from My MarketBeat watchlists, some companies that other Colfax investors own include Endologix (ELGX), Apache (APA), Chipotle Mexican Grill (CMG), Aegean Marine Petroleum Network (ANW), AutoZone (AZO), Accenture (ACN), Charles Schwab (SCHW), UMB Financial (UMBF), Agree Realty (ADC) and Gran Tierra Energy (GTE).
Who are Colfax's key executives?
Colfax's management team includes the folowing people:
Mr. Mitchell P. Rales, Co-Founder & Chairman (Age 62)
Mr. Matthew L. Trerotola, Pres, CEO & Director (Age 52)
Mr. Christopher M. Hix, Sr. VP of Fin., CFO & Treasurer (Age 57)
Mr. Daniel A. Pryor, Exec. VP of Strategy & Bus. Devel. (Age 51)
Mr. Shyam Kambeyanda, Sr. VP (Age 48)
Who are Colfax's major shareholders?
Colfax's stock is owned by a variety of of institutional and retail investors. Top institutional shareholders include Wedge Capital Management L L P NC (1.15%), Triad Investment Management (0.07%), State of Alaska Department of Revenue (0.01%) and Cerebellum GP LLC (0.01%). Company insiders that own Colfax stock include A Lynne Puckett, Christopher M Hix, Daniel A Pryor, Ian Brander, Jason Maclean, Lynn H Clark, Matthew L Trerotola, Rajiv Vinnakota and Shyam Kambeyanda. View Institutional Ownership Trends for Colfax.
Which major investors are selling Colfax stock?
CFX stock was sold by a variety of institutional investors in the last quarter, including Wedge Capital Management L L P NC, Triad Investment Management and State of Alaska Department of Revenue. Company insiders that have sold Colfax company stock in the last year include Christopher M Hix, Daniel A Pryor, Ian Brander, Lynn H Clark, Matthew L Trerotola and Shyam Kambeyanda. View Insider Buying and Selling for Colfax.
Which major investors are buying Colfax stock?
CFX stock was purchased by a variety of institutional investors in the last quarter, including Cerebellum GP LLC. View Insider Buying and Selling for Colfax.
How do I buy shares of Colfax?
Shares of CFX can be purchased through any online brokerage account. Popular online brokerages with access to the U.S. stock market include Vanguard Brokerage Services, TD Ameritrade, E*TRADE, Robinhood, Fidelity and Charles Schwab.
What is Colfax's stock price today?
One share of CFX stock can currently be purchased for approximately $38.07.
How big of a company is Colfax?
Colfax has a market capitalization of $4.48 billion and generates $3.67 billion in revenue each year. The industrial products company earns $140.20 million in net income (profit) each year or $2.31 on an earnings per share basis. Colfax employs 15,500 workers across the globe.View Additional Information About Colfax.
What is Colfax's official website?
The official website for Colfax is http://www.colfaxcorp.com/.
How can I contact Colfax?
Colfax's mailing address is 420 NATIONAL BUSINESS PARKWAY 5TH FLOOR, ANNAPOLIS JUNCTION MD, 20701. The industrial products company can be reached via phone at 301-323-9000.
MarketBeat Community Rating for Colfax (NYSE CFX)
MarketBeat's community ratings are surveys of what our community members think about Colfax and other stocks. Vote "Outperform" if you believe CFX will outperform the S&P 500 over the long term. Vote "Underperform" if you believe CFX will underperform the S&P 500 over the long term. You may vote once every thirty days.

redpajama_set_name: RedPajamaCommonCrawl


text:
Grolle (ou grole en nouvelle orthographe) est un mot servant à dénommer deux objets artisanaux en bois typiques des Alpes nord-occidentales, en particulier de la Savoie et de la Vallée d'Aoste.

Description
En Savoie, le mot grolle indique un bol en bois à becs multiples qui sert à boire un mélange de café et d'eau de vie.

En Vallée d'Aoste, ce terme définit un vase en bois sculpté, alors que le récipient pour boire le café à la valdôtaine est dénommé en français valdôtain Coupe de l'amitié. Le mot grolle est toutefois utilisé improprement pour indiquer ce dernier récipient aussi.

Autour du trou central, orné d'un couvercle sculpté, on trouve de deux à plusieurs trous appelés becs, toujours en nombre pair.

Étymologie
Le mot grolle dérive du latin vulgaire grolla, par l'intermédiaire du francoprovençal, qui atteste dès le  le mot grola signifiant « vieux soulier » et grolier signifiait « savetier », d'où l'utilisation du mot grolles pour désigner des chaussures.

Histoire
La grolle est originaire de la Vallée d'Aoste. Dans le Valais, un vase en bois appelé graoula possède la même fonction que la grolle valdôtaine

Utilisation
On y boit un mélange de café, de gnôle et de sucre, éventuellement agrémenté de zestes d'oranges et de citrons. Cette recette est appelée café à la cogneintse en Vallée d'Aoste.

Chaque participant boit à son tour par l'un des becs, avant de passer la coupe de l'amitié à son voisin, afin de ne pas en renverser, en buvant par le bec choisi, dans le sens inverse des aiguilles d'une montre. Il convient alors de boucher les deux becs adjacents avec ses pouces. La coutume veut que la coupe de l'amitié ne soit pas reposée sur la table tant qu'elle n'est pas vide.

Notes et références

Voir aussi

Biographie

Articles connexes
 Institut valdôtain de l'artisanat de tradition

Liens externes
 La Coupe de l'amitié et la Grolla

Cuisine savoyarde
Culture en Savoie
Culture dans la Vallée d'Aoste
Cuisine valdôtaine
Tradition italienne

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text:
Мухорем Хускович (; ) — австрийский футболист боснийского происхождения, нападающий клуба «Аустрия».

Клубная карьера
Хускович — воспитанник клубов «Кремсер» и венской «Аустрии». В 2020 году для получения игровой практики Мухорем начал выступать за дублирующий состав последних. 26 января 2021 года в матче против «Адмира Ваккер Мёдлинг» он дебютировал в австрийской Бундеслиге. 31 октября в поединке против «Тироль» Мухорем забил свой первый гол за «Аустрию».

Примечания

Футболисты Австрии
Игроки ФК «Аустрия» Вена


text:
Couples That Split Childcare Duties Have Higher Quality Relationships and Sex Lives
Heterosexual couples that split childcare duties have higher quality relationships and sex lives than those who don't, according to new research that will be presented at the 110th Annual Meeting of the American Sociological Association (ASA).
Does Owning a Well Foster Environmental Citizenship? A New Study Provides Evidence
Kansans who own water wells show more awareness of state water policy issues than those who rely on municipal water supplies, according to a study that could have implications for groundwater management and environmental policies.
Brock Ternes, a University of Kansas doctoral student in sociology, found that well owners prioritized issues related to the depletion of the High Plains Aquifer — which is the underground reservoir of freshwater beneath much of the western half of the state.
Study Examines Families' Journeys to Accepting Transgender Children, Mothers Play Key Advocacy Role
A tiny hair barrette and an anguished moment marked the turning point for one mother in coming to fully accept that her child, who was born a boy, was a transgender girl.
Quinn had expressed a preference for girls' clothing and accessories at a young age, but Jessica and her husband, Steve, would not allow her to wear them outside their home.
One day, picking her up from school, Jessica watched Quinn quickly remove a barrette from her hair and slip it into her pocket, ashamed that her mother might have seen.
Taking Time-Off Work to Raise Children is Damaging to the Careers of Highly Skilled, High Earning Women
Mothers who leave work to raise children often sacrifice more than the pay for their time off; when they come back their wages reflect lost raises, according to a new study by Paula England, Professor of Sociology at New York University.
Protests with Many Participants and Unified Message Most Likely to Influence Politicians, Study Suggests
Protests that bring many people to the streets who agree among themselves and have a single message are most likely to influence elected officials, suggests a new study.
"We found that features of a protest can alter the calculations of politicians and how they view an issue," said Ruud Wouters, an assistant professor of political communication and journalism at the University of Amsterdam and the lead author of the study. "More specifically, the number of participants and unity are the characteristics of a protest that have the greatest ability to change politicians' opinions."
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Since 1996 Niko has had the privilege of bringing high quality, custom made apparel to its clients, made in Canada. With deep roots in the community, we take pride in our dedicated staff and the positive effects of keeping manufacturing local.
Building on a strong foundation of experienced industry veterans, and drawing on the talent of young innovative designers, Niko can take your concept and create a brand from the ground up. From a sketch on a cocktail napkin to a fully realized garment, our designers know how to bring designs to life.
We wear our work. With over 20 years of experience creating custom tailored, technical garments, Niko constantly strives to be ahead of the curve. Every year sees new, improved equipment enter our shop, increasing our ability to deliver competitive, on trend apparel, quicker, faster and more efficiently.


We are a local affiliate of a national not-for-profit organization whose mission is to promote a vision of confidence and self sufficiency.
Girls Inc. has a college prep program (Educational Talent Search, aka ETS) that provides educational counseling in 8 Memphis City Schools. The program focuses on low income, first generation bound college students in grades 7 – 12 to help them build awareness of the importance of post secondary education and training.


text:
Difference Between Almond meal and Almond flour
• Categorized under Food | Difference Between Almond meal and Almond flour
Almond meal by hand
Almond Meal vs. Almond Flour
Almond meal and almond flour are two baking items that often stir confusion even among baking enthusiasts who have been using either for some time. Most people who are already familiar with these would nonchalantly say they are one and the same – and generally speaking, they are. However, there is one minor but tricky preparation step that is often missed out that, incidentally, is also what makes almond meal and almond flour not quite the same.
Almond flour is a term pertaining to ground blanched (without the skin) almonds. It is produced by discarding the thin layer of skin from the almonds and grinding them until the mass forms a consistency similar to regular flour. The use of almond flour can be traced back to as early as the medieval ages. It was as an alternative to wheat flour, used as a thickener or base for cakes, puddings, and other European pastries. Today, almond flour is becoming more popular, especially with health-conscious consumers. Its unique selling property is that it is gluten free. It has a highly favorable glycemic index, as it is low in carbohydrates and sugars but high in protein. It is a good source of iron, calcium, vitamin E, fiber, and cholesterol-lowering agents.
Almond meal is also produced through grinding almonds. However, instead of using blanched almonds, the skin is left on. Because of this, almond meal is slightly rougher in consistency as compared to almond flour. In most cases, especially when produced commercially, almond meal is made with solid almond residue derived through the almond oil extraction process. Because the oil, separately sold as almond flavoring, has mostly been taken away, the end-result is drier and courser than almond flour. Nevertheless, it is also a healthier alternative to wheat flour and shares almost the same gluten-free nutritional value as that of almond flour. It suits pastries that call for drier and courser texture, such as cream puff and crisp wafer bases.
Blanched Almond Flour
Both almond flour and almond meal can be purchased in supermarkets. They are also widely available and mostly more affordable in online stores. Baking experts don't greatly recommend commercially produced variations as these may already contain unwanted extenders such as wheat flour. Instead, they prefer to use homemade almond flour or meal. Almond flour can be made by carefully removing the almond skin and whizzing the almonds into a food processor or blender until they're finely ground. The procedure requires precise timing as grinding them for an extended period of time can result in almond butter. Almond meal production entails similar steps; however, the almonds don't need to be blanched.
Commercially produced or homemade almond flour and meal can be stored up to approximately 3 months. It is best to keep them refrigerated and tight-sealed in plastic bags or containers, as they tend to absorb odors from other food items. In addition, freezing them while tightly sealed can extend their shelf life.
Almond flour and almond meal are baking ingredients used as healthier alternatives to wheat flour.
Almond flour is made from finely ground, blanched almonds, while almond meal is made from finely ground almonds including the skin.
Almond flour is best used for cakes, cookies, and other pastries requiring finer, moister texture. Almond meal best suits dryer and courser pastries, such as cream puff and wafer bases.
Both are gluten-free, high in protein, and low in carbohydrates and sugars. They include essential nutrients like iron, calcium, vitamin E, and fiber.
Both can be purchased at supermarkets and online stores. They can also be homemade.
Tight-sealed and refrigerated, they can have a shelf life of up to 3 months.
Difference Between Almond Flour and Ground Almonds
Difference Between All Purpose Flour and Cake Flour
Difference Between Cake flour and All-purpose flour
Difference Between Almond Paste and Marzipan
Difference Between Bread flour and All-purpose flour
Difference Between Cake Flour and Pastry Flour
Celine. "Difference Between Almond meal and Almond flour." DifferenceBetween.net. November 6, 2018 < http://www.differencebetween.net/object/comparisons-of-food-items/difference-between-almond-meal-and-almond-flour/ >.
julie gonzalez
January 1, 2013 • 4:16 pm
"But there is one minor but tricky preparation step that is often missed out that, incidentally, is also the reason that makes almond meal and almond flour not quite the same."
I did not see this reference explained it the article.
Read more: Difference Between Almond meal and Almond flour | Difference Between | Almond meal vs Almond flour http://www.differencebetween.net/object/comparisons-of-food-items/difference-between-almond-meal-and-almond-flour/#ixzz2GkzACe7m
Written by : Celine. and updated on November 6, 2018
[0]https://www.flickr.com/photos/goosmurf/2154529152
[1]https://www.flickr.com/photos/magro-family/4840743819
See more about : almond, Baking, Baking ingredients
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text:
Girls' Generation's YoonA is the Top Earning "Girl Group Center"
It was revealed on the July 12 episode of SBS E! "K-STAR News" that Girls' Generation's YoonA was the highest-earning "girl group center" member in all of K-Pop. The "center" member is widely regarded as the most visually appealing, and in a lot of cases most popular member of the group.
According to the report, YoonA topped the likes of miss A's Suzy, After School's Uee, Kara's Goo Hara, and Wonder Girls' Sohee in terms of total income. YoonA has been able to rake in over 4 billion Korean won (approximately $3.5 million USD) in the first half of 2012. The majority of the revenue came in from TV ads, as she appeared in a total of 20 CFs for an average appearance fee of over 10 million won (approximately $9,000 USD) per ad.
YoonA is also under salary as part of the Girls' Generation, but all nine members equally distribute their total revenue, so her CF appearances played a big role in winning this honor. Currently, YoonA is under contract with cosmetic brand "Innisfree," outdoor brand "Eider," and the water purifier "Woongjin Coway," among many others.
Sohee


Twitter and Facebook are all too aware that they've been infiltrated by Russia-backed bots.
Twitter, for its part, has purged tens of thousands of accounts associated with Russia's meddling in the 2016 US presidential election. The company also said it would email notifications to hundreds of thousands of US users that followed any of the accounts created by the Russian government-linked propaganda factory known as the Internet Research Agency (IRA), and has said that it's trying to get better at detecting and blocking suspicious accounts. (As of January, it said it was detecting and blocking approximately 523,000 suspicious logins daily for being automatically generated).
That's not good enough, according to California lawmakers. They've introduced a bill that would give online platforms such as Facebook and Twitter three days to investigate whether a given account is a bot, to disclose that it's a bot if it is in fact auto-generated, or to remove the bot outright.
The bill would make it illegal for anyone to use an automated account to mislead the citizens of California or to interact with them without disclosing that they're dealing with a bot. Once somebody reports an illegally undisclosed bot, the clock would start ticking for the social media platform on which it's found. The platforms would also be required to submit a bimonthly report to the state's Attorney General detailing bot activity and what corrective actions were taken.
According to Bloomberg, the legislation is slated to run through a pair of California committees later this month.
California feels a bit guilty about how our hometown companies have had a negative impact on society as a whole. We are looking to regulate in the absence of the federal government. We don't think anything is coming from Washington.
New York is also tired of waiting for the Feds to push social media companies into fixing the bot problem. Governor Andrew Cuomo is backing a bill that would require transparency on who pays for political ads on social media.
Proposed legislation at the Federal level includes the bipartisan-supported Honest Ads Act, a proposal to regulate online political ads the same way as television, radio and print, with disclaimers from sponsors.
California's proposed bill steps it back to the processes that disseminate the content in the first place, but the online platforms say it can be tough to tell human from bot accounts run by ever more sophisticated technologies.
But there are signs to look out for. Twitter has said it's developed techniques for identifying malicious automation, such as near-instantaneous replies to tweets, non-random tweet timing, and coordinated engagement. It's also improved the phone verification process and introduced new challenges, including reCAPTCHAs, to validate that a human is in control of an account.
Investing further in machine-learning capabilities that help detect and mitigate the effect on users of fake, coordinated, and automated account activity.
Limiting the ability of users to perform coordinated actions across multiple accounts in TweetDeck and via the Twitter API.
Continuing the expansion of its developer onboarding process to better manage the use cases for developers building on Twitter's API. This, Twitter said, will help improve how it enforces policies on restricted uses of developer products, including rules on the appropriate use of bots and automation.
Researchers have also been working to come up with a set of tell-tale signs that indicate when non-humans are posting. A 2017 study estimated that as many as 15% of Twitter accounts are bots.
That paper, from researchers at Indiana University and the University of Southern California, also outlines a proposed framework to detect bot-like behavior with the help of machine learning. The data and metadata they took into consideration included social media users' friends, tweet content and sentiment, and network patterns. One behavioral characteristic they noticed, for example, was that humans tend to interact more with human-like accounts than they do with bot-like ones, on average. Humans also tend to friend each other at a higher rate than bot accounts.
Mind you, not all bots are bad. Take Emoji Aquarium: it's a bot that shows you a tiny aquarium "full of interesting fishies" every few hours.
Good bots are also useful: they help keep weather, sports, and other news updated in real-time, and they can help find the best price on a product or track down stolen content.
And then too, there's Bot Hertzberg: the bot created by California Senator Bob Hertzberg to highlight the issue. Hertzberg introduced the pending California bot bill.
We need to know if we are having debates with real people or if we're being manipulated. Right now, we have no law, and it's just the Wild West.
This is privacy and freedom of speech. You can say what you want. You can larp fake news all you want. This law is unconstitutional.
The only way they can operate with a law like this is to have some sort of ministry of truth that tells YOU what is legit and what is not legit news. Totally not going to see something like that abused by either side right?
Freedom means that the freedom to be dumb is also there. As smart people you simply need to be able to understand that a forum which is open to anyone may have knuckleheads in there that mislead. Verify sources, don't believe everything you read, do your own research. Stop trying to pass laws that strip freedoms and put in place government filtering which can be subject to abuse by those who hold the power to do so. You know, not something that politicians ever do right?
Not exactly – the deal with bots is that they aren't real accounts (in other words, they weren't created in accordnce with the terms of service that other users might reasonably expect to be enforced).
If you open a bank account with fake ID, even if you aren't a crook and only ever deposit lawfully-acquired, tax-paid money, then the bank is obliged to report your bogosity if it finds out. In other words, this isn't so much to do with what you say, but how you go about sneakily wangling ways to say it.
If they "weren't created in accordance with the terms of service " (I fixed the missing "a") then they are already breaking the TOS, and potentially criminal, no additional laws needed.
Didn't know there was anything criminal about lying to a site. Maybe get you kicked off but not criminally prosecution.
I think the answer is (depends on jurisdiction) that "it's underscored by what your motivation was" – like the difference in England between trespass (e.g. where you take a shortcut across someone's land even though you know it's private – a civil matter that the police can't and won't get involved in) and criminal trespass (e.g. where you do onto their property with nefarious or disruptive intent – where the cops can attend, arrest you and cart you off).
Here in the USA you are pretty safe if you pay taxes. That's what screwed up Al Capone, got busted for income tax evasion. EULA's are like most contracts, there to protect the company, not the user.
I guess they can't check the "I'm not a bot" box….
This type of legislation could be questionable. The Internet is FULL of bots doing useful things that we depend on. How is a 'bot' defined legally? The difference between a 'good' bot and a 'bad' bod? I think, like other prohibition issues, this may be a loosing battle. How do you determine the country of origin and what they are doing?
Both of these companies knew this was going on, where were my protections? In the companies bank account.
The US has not protected it's citizens from any cyber threats via legislation compared to the European countries. Unfortunately some laws may not work as expected. This may be much more complex than it sounds.


Using Disney PhotoPass photographers is one of my absolute favorite vacation conveniences. I don't have to worry about trying to capture the memories of our perfect trip and better yet, I get to be in the pictures instead of behind the camera!
One of the best features of the Disney PhotoPass Memory Maker is the ability to have everyone under your reservation, and those you link through your My Disney Experience- My Family & Friends list, able to save those precious moments to your Disney PhotoPass account. There are just a few simple steps you will need to complete to make sure everything is set up correctly and then, just smile and enjoy your vacation.


A ubiquitous Knowledge Base (u-KB) is a distributed and decentralized knowledge base where the factual knowledge (i.e. individuals) is scattered between objects disseminated within a given environment with no centralized coordination. Such a vision enables a truly pervasive environment where autonomous objects set up a self-organized discovery architecture. This paper presents an extended framework to set-up u-KBs. An advanced semantic matchmaking makes possible resource discovery based on metadata stored in RFID (Radio Frequency IDentification) tags without pre-stored and fixed repositories and a dissemination protocol allows an ondemand retrieval of suitable resource descriptions directly from tags located on the objects.
Ruta, M., Sciascio, E. D., Piscitelli, G., Scioscia, F. (2010). " A Ubiquitous Knowledge-based System to Enable RFID Object Discovery in Smart Environments "Pacific Asia Journal of the Association for Information Systems, 2(3), pp.21-49.


How did you get involved with programming?
Our sister Cathy Han who runs a tech business in Silicon Valley encouraged us to learn programming. After some formal training, we hired a private tutor from the University of Calgary to hone our skills. That led to competing at international hackathons including Vegas Money 20/20, where we built a calculator and bank account simulator in 24 hours. We also participated in the Mayor's Youth Council hackathon, where we built an app for youth to engage in city amenities like our public libraries.
Why is programming an important skill?
Computer science and artificial intelligence are going to be the next big things in the future. They will be controlling everything we do. With programming skills, you can contribute to the advancement of areas like medicine and agriculture and impact lives.
At the hackathons, less than 10% of the participants were female, which highlighted the need for more females in STEM (Science, Technology, Engineering, and Math).
Although there were programmers who had graduated from universities like MIT and Stanford, we stood on those hackathon stages and won prizes. Age and gender should never be a barrier to anything.
How do you see this skill showing up in current and future work?
Schools are already integrating coding classes into their curriculums. Soon, we believe skills like programming will become mainstream in the classroom, especially in the younger grades. Learning to program is the same process as learning another language; it takes a lot of practice and practical application.
How do you see programming fitting into your lives in the next several years?
We both hope to incorporate computer science and software engineering into our careers.
What advice would you give to youth wanting to get involved in tech or tech projects?
GO FOR IT. Start early. Learn with friends. Don't be afraid to try it out! Find someone who knows the world of tech and learn firsthand. If you fail, you'll learn from your mistakes and use them to improve your future.


text:
Q: Passing context "this" from one function into another inside it? I'm practicing ajax with forms, and.. I guess trying to confuse myself more and more for the sake of learning.
This might not make any sense, but I'm trying to log the first and last name, specifically through the conLog function. But it's showing as undefined because I think the context "this" is not there, and I'm not sure how to set it. I managed to set it inside the ajax however.
So if you open the log, the 2nd line says undefined, while in the first, the input from the first form is logged.
https://jsfiddle.net/2oLjqv7c/3/
Assuming that's the problem, how do I pass "this" into conLog?
thanks in advance! and I found a few posts with the same question, but sigh... I guess I can't grasp it unless if it's applied to my personal problem (still need to learn to read other people's codes I guess).
HTML
<form action="/echo/html/" id="form1" method="post">
  First Name:
  <input type="text" value="first" id="firstName">

  Last Name:
  <input type="text" value="last" id="lastName">

  <button type="submit" form="form1" value="submit">Submit</button>
</form>

Javascript/jQuery
function Display(el) {
    this.el = el;
  this.firstName = this.el.find("#firstName");
  this.lastName = this.el.find("#lastName");
  var confirmation = this;
    this.el.on('submit', function(e) {
        e.preventDefault();
    $.ajax('/echo/html/', {
        success: function() {
        console.log('success' + " " + this.firstName.val());
        this.conLog(this.firstName.val(), this.lastName.val());
      },
      error: function() {
        console.log('fail');
      },
      timeout: 3000,
      context: confirmation
    });
  });

  this.conLog = function(first, last) {
    this.first = this.first;
    this.last = this.last;
    console.log(this.first + " " + this.last);
  };
}

$(document).ready(function() {
    Display($('#form1'));
})

A: I guess this is what you're looking for.
I modified your fiddle to output the name to a
 element.
I just modified how the props of consLog are assigned:
  this.conLog = function(first, last) {
    this.first = first;
    this.last = last;
    console.log(this.first + " " + this.last);
    document.getElementById("name").innerHTML = this.first + " " + this.last;
  };

A: You don't need to pass this.  Because you're already passing the first and last parameters.  Just use those directly like this:
this.conLog = function(first, last) {
  console.log(first + " " + last);
};

Note I changed this.first and this.last to just first and last.

A: So there are quite a few ways to achieve this... one of the easiest is to set var self = this; above or around where you have this.el = el; and no matter how deep down your functions are you can always use this reference to it by taking advantage of Javascript's functional scope. If like you say you are learning i suggest you look into Function.bind Function.call and Function.apply which all relate to your question... MDN is always a great place to start..

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text:
Desa Manggis kan syfta på följande platser:

Indonesien

 Desa Manggis (administrativ by i Indonesien, Provinsi Bali),
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Robotskapade Indonesienförgreningar


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The Swansea Wastewater Networks team recently carried out a large sewer repair at Baglan, near Port Talbot.
After a thorough investigation, the team found a 5 metre collapse on the sewer line underneath the busy Briton Ferry roundabout on the A48 dual carriageway, which was causing problems for a nearby McDonald's restaurant.
Because of the tricky position of the collapsed line, while Network Engineer, Michael Lodwig, Wastewater Technician Gavin Ridgway and Project Manager at Peter Duffy Ltd (our contract partners), and Paul Edwards worked on a plan for the repair work, the wider Network team for the area used temporary measures to make sure that McDonalds was able to remain open, with their sewerage systems running as smoothly as possible.
To carry out the repair, the team worked closely with the South Wales Trunk Road Agency (SWTRA) and Welsh Assembly Government (WAG) to make sure that it could be completed with minimal disruption to our customers.
Peter Duffy Ltd worked around the clock, over a period of 10 days during the Easter holidays to make sure that the repair was done within the planned timescale.
Michael Lodwig said: "This was a complex emergency repair due to the location and depth of the sewer. We were grateful for the co-operation of SWTRA and WAG, and we're very pleased with the work done by Peter Duffy Ltd – their efforts have really helped us to build a trusting relationship with SWTRA and WAG for any future work.


text:
Nordkoster är en ö i ögruppen Koster i Tjärnö socken i Strömstads kommun belägen utanför Strömstad på Sveriges västkust. Det är den näst största av öarna, som ingår Kosterarkipelagen, och är mer karg och bergig än Sydkoster.

Historia
Enligt en lokal sägen skall rädsla för digerdöden ha drivit de första bosättarna att slå sig ned på öarna. Ett hushåll fanns på 1600-talet på Nordkoster. Öarna kalhöggs under 1700-talet för att ge virke åt båtvarven, och jordbruket gick dåligt men fisket, särskilt hummerfisket var betydelsefullt. Särskilt under 1800-talet fick fisket ett stort uppsving. 1917 bodde 190 personer på Nordkoster. Befolkningen har därefter minskat fram till 2005, då ön hade 105 bofasta innevånare. Det har sedan ökat något och 2012 fanns 125 bofasta.

Fyrarna
På berget Högen, också kallat Kosterbonden, 59 meter över havet, står två torn som tidigare varit fyrar. När de byggdes var de avsedda att varna skepp, som kom utifrån Skagerrak, för de farliga grundområden som sträcker sig från Ramskär i söder till Grisbådarna i norr, vid gränsen mot Norge. För att skilja fyren på Nordkoster från andra fyrar i omgivningen valde man att ha ljus i två torn. Fyrarna tändes år 1849 men de var för högt placerade. Vid god sikt togs de för stjärnor och vid dålig sikt med låga moln gick de inte att se. Flera skeppsbrott orsakades av att fyrarna inte kunde siktas.

Det beslöts att nya fyrar skulle uppföras på Ursholmen, den mest sydvästliga delen av Kosterarkipelagen. År 1891 släcktes fyrarna på Höjden. Den ena lanterninen flyttades till Ursholmen och den andra till Malören.

Efter att tornen länge stått oanvända i mer än ett hundra år monterades år 2003 en ny lanternin på det norra tornet.

Lots
På Nordkoster har det tidigare funnits en lotsstation. Den är numera indragen, men utkiken finns kvar. När lotsstationen drogs in så hade det funnits lots att tillgå på Koster så långt tillbaka som det finns skriftlig dokumentation.

Väderstation
På Nordkoster finns en av SMHI:s väderstationer. Vindobservationer från denna station omnämns i den svenska Sjörapporten.

Etymologi
År 1398 skrevs öns namn nordr Kostom. Det antas att namnet kommer av det fornnordiska kostir, som kan översättas matplatserna, och som troligen syftar på det rika fisket kring Kosteröarna.

Kosterhavets nationalpark
Nordkoster ligger omgiven av Kosterhavets nationalpark, men själva ön är privatägd och kan därför inte ingå i nationalparken.
I nationalparken ligger skäret Stora Drammen, Sveriges västligaste punkt på samma longitud som Oslo.

På nordkostern finns även Lysmossegrottan, en grotta med lysmossa.

Se även
 Koster
 Nord-Koster och Duvnäs
 Sydkoster

Referenser

Noter

Tryckta källor
 Källgård, Anders; Sveriges öar, Kristianstad 2005
 Knapp, Ted; Längs Kusten i Bohuslän, Mölndal 2006

 Wahlberg, Mats (red); Svenskt ortnamnslexikon, Stockholm 2003

Kosteröarna
Kosterhavets nationalpark
Fiskelägen
Bohusläns öar
Områden och platser i SMHI:s sjöväderrapport


WASHINGTON - Today the Federal Communications Commission (FCC) approved a telephone-pricing plan that incorporates key elements of a proposal developed by the Coalition for Affordable Local and Long Distance Service (CALLS). GTE, along with other leading local and long-distance companies, is a member of CALLS.
The following may be attributed to Charles R. Lee, chairman and chief executive officer of GTE Corp.
GTE congratulates the FCC for taking action today that will significantly boost competition in the telecommunications market and benefit consumers.
By establishing a new structure for federal access charges, the Commission's ruling is a giant step toward ultimately solving the pervasive problem of implicit subsidies preventing local phone competition.
GTE has long recognized that the traditional system of implicit subsidies that has ensured everyone receives affordable, high-quality telephone service would not work in an increasingly competitive environment. We joined a group of companies to shape an alternative, the CALLS proposal, that attempted to blend what has worked in the past to create "universal service" with what is demanded by the future.
We are very pleased that the Commission's ruling today adopts major elements of the Coalition's plan and begins to strike the balance intended by the Act between the obligation to provide "universal service" and the freedom to compete.