title: 5 October 1910 revolution

text: Two months later, with the approval of the Political Constitution of the Portuguese Republic and the election of the first constitutional president of the Republic — Manuel de Arriaga — on 24 August, the Provisional Government presented its resignation, which was accepted by the president of the republic on 3 September 1911, marking the end of a government term of more than 10 months and the beginning of the First Portuguese Republic.


title: 5 October 1910 revolution

text: With the establishment of the Republic, the national symbols were modified. By a Provisional Government decree dated 15 October 1910, a committee was appointed to design the new symbols. The modification of national symbols, according to historian Nuno Severiano Teixeira, emerged from the difficulty that republicans faced with representing the Republic:


title: 5 October 1910 revolution

text: In relation to the flag, there were two inclinations: one of keeping the blue and white colours, traditional of Portuguese flags, and another of using "more republican" colours: green and red. The committee's proposal suffered several alterations, with the final design being rectangular, with the first two-fifths closest to the flagpole to be green, and the three remaining fifths, red. Green was chosen because it was considered the "colour of hope", while red was chosen as a "combative, hot, virile" colour. The project of the flag was approved by the Provisional Government by vote on 19 November 1910. On 1 December was celebrated the Feast of the Flag in front of the Municipal Chamber of Lisbon. The National Constituting Assembly promulgated the adoption of the flag on 19 June 1911.


title: 5 October 1910 revolution

text: On 19 June 1911 the National Constitutional Assembly proclaimed "A Portuguesa" as the national anthem, replacing the old anthem "Hymno da Carta" in use since May 1834, and its status as national symbol was included in the new constitution. "A Portuguesa" was composed in 1890, with music by Alfredo Keil and lyrics by Henrique Lopes de Mendonça, in response to the 1890 British Ultimatum. Because of its patriotic character, it had been used, with slight modifications, by the rebels of the 1891 uprising in a failed attempt at a "coup d'état" to establish a republic in Portugal, an event which caused the anthem to be forbidden by the monarchic authorities.


title: 5 October 1910 revolution

text: The anthem was later modified; the official version used today in national civil and military ceremonies and during visits of foreign heads of state was approved on 4 September 1957.


title: 5 October 1910 revolution

text: The official bust of the Republic was chosen through a national competition promoted by Lisbon's city council in 1911, in which nine sculptors participated. The winning entry was that of Francisco dos Santos and is currently exposed in the Municipal Chamber. The original piece is found in Casa Pia, an institution from which the sculptor was alumnus. There is another bust that was adopted as the face of the Republic, designed by José Simões de Almeida (sobrinho) in 1908. The original is found in the Municipal Chamber of Figueiró dos Vinhos. The model for this bust was Ilda Pulga, a young shop employee from Chiado. According to journalist António Valdemar, who, when he became president of the National Academy of Art asked the sculptor João Duarte to restore the original bust:


title: 5 October 1910 revolution

text: The bust shows Republic wearing a Phrygian cap, influence of the French Revolution. Simões' bust was soon adopted by Freemasonry and used in the funerals of Miguel Bombarda and Cândido dos Reis, but when the final contest took place, despite its relative popularity, it was second place to the bust by Francisco dos Santos.


title: 5 October 1910 revolution

text: Republican leaders adopted a severe and highly controversial policy of anti-clericalism. At home, the policy polarised society and lost the republic potential supporters, and abroad it offended American and European states which had their citizens engaged in religious work there, adding substantially to the republic's bad press. The persecution of the church was so overt and severe that it drove the irreligious and nominally religious to a new religiosity and gained the support of Protestant diplomats such as the British, who, seeing their citizens' religious institutions in a grave dispute over their rights and property, threatened to deny recognition of the young republic. The revolution and the republic which it spawned were essentially anticlerical and had a "hostile" approach to the issue of church and state separation, like that of the French Revolution, the Spanish Constitution of 1931 and the Mexican Constitution of 1917.


title: 5 October 1910 revolution

text: Secularism began to be discussed in Portugal back in the 19th century, during the Casino Conferences in 1871, promoted by Antero de Quental. The republican movement associated the Catholic Church with the monarchy, and opposed its influence in Portuguese society. The secularisation of the Republic constituted one of the main actions to be taken in the political agenda of the Portuguese Republican Party and the Freemasonry. Monarchists in a last-ditch effort sought to outflank the republicans by enacting anticlerical measures of their own, even enacting a severe restriction on the Jesuits on the day before the revolution.


title: 5 October 1910 revolution

text: Soon after the establishment of the Republic, on 8 October 1910, Minister for Justice Afonso Costa reinstated Marquess of Pombal's laws against the Jesuits, and Joaquim António de Aguiar's laws in relation to religious orders. The Church's property and assets were expropriated by the State. The religious oath and other religious elements found in the statutes of the University of Coimbra were abolished, and matriculations into first year of the Theology Faculty were cancelled, as were places in the Canon law course, suppressing the teaching of Christian doctrine. Religious holidays turned into working days, keeping however the Sunday as a resting day for labour reasons. As well as that, the Armed forces were forbidden from participating in religious solemn events. Divorce and family laws were approved which considered marriage as a "purely civil contract"


title: 5 October 1910 revolution

text: Bishops were persecuted, expelled or suspended from their activities in the course of the secularisation. All but one were driven from their dioceses. the property of clerics was seized by the state, wearing of the cassock was banned, all minor seminaries were closed and all but five major seminaries. A law of 22 February 1918 permitted only two seminaries in the country, but they had not been given their property back. Religious orders were expelled from the country, including 31 orders comprising members in 164 houses (in 1917 some orders were permitted to form again). Religious education was prohibited in both primary and secondary school.


title: 5 October 1910 revolution

text: In response to the several anticlerical decrees, Portuguese bishops launched a collective pastoral defending the Church's doctrine, but its reading was prohibited by the government. In spite of this, some prelates continued to publicise the text, among which was the bishop of Porto, António Barroso. This resulted in him being called to Lisbon by Afonso Costa, where he was stripped from his ecclesiastic functions.


title: 5 October 1910 revolution

text: The secularisation peaked with the "Law of Separation of the State and the Church" on 20 April 1911, with a large acceptance by the revolutionaries. The law was only promulgated by the Assembly in 1914, but its implementation was immediate after the publishing of the decree. The Portuguese Church tried to respond, classifying the law as "injustice, oppression, spoliation and mockery", but without success. Afonso Costa even predicted the eradication of Catholicism in the space of three generations. The application of the law began on 1 July 1911, with the creation of a "Central Commission". As one commentator put it, "ultimately the Church was to survive the official vendetta against organized religion".


title: 5 October 1910 revolution

text: On 24 May 1911, Pope Pius X issued the encyclical Iamdudum which condemned the anticlericals for their deprivation of religious civil liberties and the "incredible series of excesses and crimes which has been enacted in Portugal for the oppression of the Church."


title: 5 October 1910 revolution

text: A major concern of the new republican government was recognition by other nations. In 1910, the vast majority of European states were monarchies. Only France, Switzerland and San Marino were republics. For this reason, the Minister of Foreign Affairs of the Provisional Government, Bernardino Machado, directed his agenda exercising extreme prudence, leading him, on 9 October 1910, to communicate to diplomatic representatives in Portugal that the Provisional Government would honour all the international commitments assumed by the previous regime.


title: 5 October 1910 revolution

text: Since marshal Hermes da Fonseca personally witnessed the full process of transition of the regime, having arrived in Portugal on an official visit when the country was still a monarchy and left when it was a republic, it is not unusual that Brazil was the first country to recognise "de jure" the new Portuguese political regime. On 22 October the Brazilian government declared that "Brazil will do all that is possible for the happiness of the noble Portuguese Nation and its Government, and for the prosperity of the new Republic". The next day would be Argentina's turn; on the 29 it was Nicaragua; on the 31, Uruguay; on 16 and 19 November, Guatemala and Costa Rica; Peru and Chile on 5 and 19 November; Venezuela on 23 February 1911; Panama on 17 March. In June 1911 the United States declared support.


title: 5 October 1910 revolution

text: Less than a month after the revolution, on 10 November 1910, the British government recognised "de facto" the Portuguese Republic, manifesting "the liveliest wish of His Britannic Majesty to maintain friendly relations" with Portugal. An identical position was taken by the Spanish, French and Italian governments. However, "de jure" recognition of the new regime only emerged after the approval of the Constitution and the election of the President of the Republic. The French Republic was the first to do it on 24 August 1911, day of the election of the first president of the Portuguese Republic. Only on 11 September did the United Kingdom recognise the Republic, accompanied by Germany, the Austro-Hungarian Empire, Denmark, Spain, Italy and Sweden. On 12 September, they were followed by Belgium, the Netherlands and Norway; on 13 September, China and Japan; on 15 September, Greece; on 30 September, Russia; on 23 October, Romania; on 23 November, Turkey; on 21 December, Monaco; and on 28 February 1912, Siam. Owing to the tensions created between the young Republic and the Catholic Church, interaction with the Holy See was suspended, and the Holy See did not recognise the Portuguese Republic until 29 June 1919.


title: Bruce Cabot

text: Bruce Cabot (born Étienne de Pelissier Bujac Jr.; April 20, 1904 – May 3, 1972) was an American film actor, best remembered as Jack Driscoll in "King Kong" (1933) and for his roles in films such as "The Last of the Mohicans" (1936), Fritz Lang's "Fury" (1936), and the Western "Dodge City" (1939). He was also known as one of "Wayne's Regulars", appearing in a number of John Wayne films beginning with "Angel and the Badman" (1947), and concluding with "Big Jake" (1971).


title: Bruce Cabot

text: Cabot was born in Carlsbad, New Mexico, to a prominent local lawyer, Major Étienne de Pelissier Bujac Sr. and Julia Armandine Graves, who died shortly after giving birth to her son. Étienne Sr. was the son of John James Bujac, a lawyer and mining expert in Baltimore, Maryland. Étienne Sr. graduated from Cumberland School of Law near Nashville, Tennessee, and served in the United States Army during the Spanish–American War and the Philippine–American War before settling in Carlsbad.


title: Bruce Cabot

text: Cabot graduated from Sewanee Military Academy in 1921, and briefly attended the University of the South in Sewanee, Tennessee, but left without graduating. He worked at many jobs, including as a sailor, an insurance salesman, oil worker, surveyor, and prize fighter; he also sold cars, managed real estate, and worked at a slaughterhouse. A meeting with David O. Selznick at a Hollywood party led to his acting career.


title: Bruce Cabot

text: Cabot appeared in nearly 100 feature films. He made his debut in an uncredited bit part in an episode of the serial "Heroes of the Flames" (1931). In "Ann Vickers" (1933), he portrays a soldier who seduces a naive woman (Irene Dunne), and gets her pregnant before he leaves for the war. He then appeared in "King Kong" (also 1933), which became an enormous success and established Cabot as a star.


title: Bruce Cabot

text: He also portrays villains in several productions, appearing as a gangster boss in "Let 'Em Have It" (1935) and as the Huron warrior Magua opposite Randolph Scott in "The Last of the Mohicans" (1936). He co-stars with Spencer Tracy in Fritz Lang's first Hollywood film, "Fury" (1936), playing the leader of a lynch mob. He also appears with Errol Flynn in Michael Curtiz's epic Western "Dodge City", which in 1939 was one of Warner Bros.'s biggest hits.


title: Bruce Cabot

text: He tested for the lead role of the Ringo Kid in John Ford's "Stagecoach" (1939), but John Wayne was cast in the part. A consistent box-office draw, Cabot appeared in many movies at many studios before leaving Hollywood to serve in World War II.


title: Bruce Cabot

text: Cabot enlisted in December 1942 and, after Officer Training School in Miami Beach, was commissioned a first lieutenant in the U.S. Army Air Force.


title: Bruce Cabot

text: Cabot headed back to Hollywood and fell in with John Wayne on the set of "Angel and the Badman" (1947), and became part of Wayne's circle, this relationship paying off in the 1960s, when Wayne cast him in 10 more of his films: "The Comancheros" (1961), "Hatari!" (1962), "McLintock!" (1963), "In Harm's Way" (1965), "The War Wagon" (1967), "The Green Berets" (1968), "Hellfighters" (1968), "The Undefeated" (1969), "Chisum" (1970), and "Big Jake" (1971).


title: Bruce Cabot

text: Cabot starred in a number of the "Tales of Tomorrow", a science-fiction drama, during its second season (1952–53) on ABC.


title: Bruce Cabot

text: Cabot was married three times, in Florida to Mary Mather Smith, whom he divorced prior to moving to Hollywood, and to actresses Adrienne Ames and Francesca De Scaffa (1930-1994).


title: Bruce Cabot

text: He was one of Errol Flynn's social pack for several years, but they fell out during the production of the unfinished "The Story of William Tell". Flynn was producing the film and asked Cabot, whom he described as "an old, old pal," to appear in it, knowing that Cabot was having difficulty finding work in Hollywood at that time. When Flynn's production partners went broke, though, production on the film halted, leaving Flynn stranded in Rome facing financial ruin. Cabot, in an attempt to get paid when other cast members were working for no money, had Flynn's and his wife Patrice Wymore's personal cars and clothing in their Rome hotel seized. Flynn wrote angrily in his autobiography of what he termed Cabot's "betrayal". David Niven, also part of Flynn's social pack, in his autobiography accused Cabot of being missing when debts were to be paid.


title: Bruce Cabot

text: Cabot died May 3, 1972, at age 68 in the Motion Picture Country Home at Woodland Hills, California due to lung cancer. He was buried in his hometown of Carlsbad, New Mexico.


title: Marder III

text: "Marder" III was the name for a series of World War II German tank destroyers. They mounted either the modified ex-Soviet 76.2 mm F-22 Model 1936 divisional field gun, or the German 7.5 cm PaK 40, in an open-topped fighting compartment on top of the chassis of the Czechoslovakian Panzer 38(t). They offered little protection to the crew, but added significant firepower compared to contemporary German tanks. They were in production from 1942 to 1944, and served on all fronts until the end of the war, along with the similar Marder II. The German word "Marder" means "marten" in English.


title: Marder III

text: In the early stages of Operation Barbarossa, the Wehrmacht felt the need for a more mobile and more powerful anti-tank solution than the existing towed anti-tank guns, such as the "3.7 cm Pak 36", or self-propelled tank destroyers, such as the "Panzerjäger I" (mounted with the 4.7 cm PaK (t)). This need became urgent in 1942, when anti-tank shells fired from said anti-tank guns failed to penetrate the armor of new Soviet tanks, such as the T-34 and KV-1.


title: Marder III

text: As an interim solution, it was decided to use captured French vehicles, such as the Lorraine (Marder I), obsolete tanks in surplus, such as the German Panzer II (Marder II), and Czech-supplied Panzer 38(t) ("Marder" III) as the base for the production of makeshift tank destroyers. The result was the "Marder" series, which were armed with either captured Soviet 76.2mm F-22 Model 1936 divisional field guns, or German 7.5 cm PaK 40 anti-tank guns mounted in later versions. Due to weight, space, and time constraints, the "Marder" series had relatively thin armor when compared with other armored vehicles of the era. This thin upper armor formed a gunshield, only protecting the crew from shrapnel and small arms fire on the front and sides. All "Marder" series had open tops—although some were issued with canvas tops to protect the crew from the elements. In this regard, the Marder was more of a gun carriage than a proper Panzerjäger that could exchange fire with enemy tanks.


title: Marder III

text: While the Panzer 38(t) had largely become obsolete as a tank in early 1942, it was still an excellent and plentiful platform for adaptation into a tank destroyer, among other roles. Since the Soviet 76.2 mm field gun was captured in large quantities, the decision was made to mate this gun to the Panzer 38(t).


title: Marder III

text: To do so, the mass production of the Panzer 38(t) Ausf. G was halted, and a modified superstructure was bolted onto the standard tank chassis in lieu of a gun turret. This upper structure mounted the gun and an extended gun shield, giving only limited protection for the commander, gunner, and the loader. Armor protection overall ranged from 10 to 50 mm, with no armor at all above and behind the gun compartment, which the crew occupied. It had a higher silhouette than the original Panzer 38(t), which made it more vulnerable to enemy fire.


title: Marder III

text: In German service, the Soviet gun was redesignated 7.62 cm PaK 36(r), and rechambered for the more powerful German PaK 40 cartridge. Thirty rounds of ammunition were stored inside the vehicle. Apart from the main gun, there was a 7.92 mm machine gun mounted in the hull.


title: Marder III

text: This tank destroyer was put into production as the "Panzerjäger 38(t) für 7.62 cm PaK 36(r), Sd.Kfz. 139". A total of 344 vehicles were built in three series from April to November 1942. Chassis numbers were 1360–1479, 1527–1600, and 1601–1750.


title: Marder III

text: This next variant of the "Marder" III fielded the standard 7.5 cm PaK 40 German anti-tank gun on a slightly modified Panzer 38(t) Ausf. H chassis. This chassis still had the engine in the rear of the vehicle, but, unlike the previous model, this vehicle utilized the fighting compartment of the Panzer 38 in the center. This allowed the crew to stay low in the center of the vehicle, lowering their exposure to small arms fire and shell fragments. However, because of the rear-mounted engine, there was only enough room for two men to stand in the center. Large side armor gave additional protection for the crew. Despite this, the thin horseshoe-shaped armor only protected the front and sides; the rear and the top were exposed. Thirty-eight rounds of ammunition for the gun were carried. As with the Sd.Kfz.139, this vehicle also carried a Czech-manufactured 7.92 mm machine gun in the hull.


title: Marder III

text: The full name of the Ausf. H was the "7.5 cm PaK 40/3 auf Panzerkampfwagen 38(t) Ausf. H, "Sd.Kfz". 138". A total of 275 vehicles were built in two series from November 1942 to April 1943. An additional 175 vehicles were converted from Panzer 38(t)'s in 1943. Chassis numbers of new vehicles were 1751–2075 and 2121–2147 (overlapping with simultaneous Grille production).


title: Marder III

text: The last Marder III variant was based on the Geschützwagen 38(t) Ausf. M, a purpose-designed vehicle for self-propelled gun use, again armed with the 75 mm PaK 40 anti-tank gun. Ausf. M was the final variant of the Marder series, and was a significant improvement over previous models, with its lower silhouette, sloped armor, and much more functional fighting compartment. In this variant, the engine was moved from the rear to the middle between driver and the rest of the crew. Because there was no engine in the rear, the gun and the crew did not have to sit on top of the engine deck as in previous models. The fighting compartment could be lowered down to the bottom floor level where the engine used to be, which decreased crew exposure and visibility. Unlike the previous two "Marder" III variants, the fighting compartment was closed at the rear, protecting the crew up to their midsection. It stayed open-topped. The machine gun port at the front was eliminated in the "Ausf". M in favor of an MG 34 or MG 42 carried by the crew. In the previous two models, the commander served as a gunner. However, in the Ausf. M, the radio man moved to the rear, with the commander and gunner, to serve as a loader. Only 27 rounds of 7.5 cm ammunition were carried, but combat effectiveness increased because the vehicle commander was freed from manning the gun.


title: Marder III

text: The full name of the Ausf. M was "Panzerjäger 38(t) mit 7.5 cm PaK 40/3 Ausf. M, Sd.Kfz. 138 ". It was the variant that was produced in the largest numbers, with 942 vehicles built in two series from May 1943 to May 1944. Chassis numbers were 2166–2600 and 2601–3600 (overlapping with simultaneous Grille and Flakpanzer 38(t) production).


title: Marder III

text: The various "Marder" III’s fought on all European fronts and in North Africa, with the Sd. Kfz. 139 being used mainly at the Eastern Front, though some also fought in Tunisia. In February 1945, some 350 Ausf. M were still in service.


title: Marder III

text: The "Marder" III’s were used by the "Panzerjäger Abteilungen" of the Panzer divisions of both the Heer and the Waffen SS, as well as several Luftwaffe units, such as the Hermann Göring division.


title: Marder III

text: The "Marder" III’s were mechanically reliable, as with all vehicles based on the Czechoslovak LT-38 chassis. Their firepower was sufficient to destroy the majority of Soviet tanks on the battlefield at combat range.


title: Marder III

text: The "Marder" III's weaknesses were mainly related to survivability. The combination of a high silhouette and open-top armor protection made them vulnerable to indirect artillery fire. The armor was also quite thin, making them highly vulnerable to enemy tanks, and to close-range machine gun fire.


title: Marder III

text: The Marders were not assault vehicles or tank substitutes; the open top meant that operations in urban areas or other close-combat situations were very risky. They were best employed in defensive or overwatch roles. Despite their mobility, they did not replace the towed antitank guns.


title: Marder III

text: In March 1942, before the "Marder III" appeared, Germany had already started production of the "StuG III" assault gun, which had comparable anti-tank capability ("StuG III Ausf. F" and later variants). These were fully armored vehicles, with the fighting compartment fully enclosed within an armored casemate, built in much greater numbers than the vulnerable "Marder III". Among the many German casemated tank destroyers, one based on the Panzer 38(t) chassis was built in numbers from 1944: the "Jagdpanzer 38(t)". The weakly-armored Marder series were phased out of production in favor of the Jagdpanzer 38(t), but Marder series vehicles served until the end of the conflict.


title: Marder III

text: In June 1944, the army of the Slovak Republic received 18 "Marder" III Ausf. H. Four of them saw combat during the Slovak National Uprising. Two vehicles were used by the partisan brigade "Čapajev". One of them was destroyed between the towns Vranov nad Topľou and Prešov. The second Marder was used in heavy fights near Hermanovce nad Topľou. Its commander, Rajták, suffered a gunshot wound, and the vehicle was subsequently abandoned.


title: Marder III

text: The remaining two Marders were used by the Slovak insurgent army near Strečno, and they played an important role in the Battle of Strečno Gorge. One of the Marders, under the command of Private Matej Buc, destroyed three German tanks and two anti-tank guns. During the German assault on 3 September, Commander Matej Buc and loader Štefan Kováč, who were sitting in an open hull, were shot. However, the driver, František Smolnický, survived and escaped from the battlefield with the vehicle. It was repaired and reused in battle, but on 8 and 9 September, both Marders were destroyed in battle—one near Vrútky, and other one near Priekopa.


title: Raw milk

text: Raw milk or unpasteurized milk is milk that has not been pasteurized, a process of heating liquid foods to kill pathogens for safe consumption and extending the shelf life.


title: Raw milk

text: Proponents of raw milk have asserted numerous supposed benefits to consumption, including better flavor, better nutrition, contributions to the building of a healthy immune system and protection from allergies. However, no clear benefit to consumption has been found, and the medical community notes there is increased risk of contracting dangerous milk borne diseases from these products substantial evidence of this increased risk, combined with a lack of any clear benefit, has led countries around the world to either prohibit the sale of raw milk or require warning labels on packaging when sold.


title: Raw milk

text: In countries where it is available for sale, its availability and regulations around its sale vary. In the EU, member states can prohibit or restrict the sale of raw milk, but it is not banned outright; in some member states, the sale of raw milk through vending machines is permitted, though the packaging will typically instruct consumers to boil before consumption. In the US, some dairies have adopted "low-temperature vat pasteurization", which they say produces a product similar to raw milk.


title: Raw milk

text: Humans first learned to regularly consume the milk of other mammals following the domestication of animals during the Neolithic Revolution or the development of agriculture. This development occurred independently in several places around the world from as early as 9000–7000 BC in Mesopotamia to 3500–3000 BC in the Americas. The most important dairy animals—cattle, sheep and goats—were first domesticated in Mesopotamia, although domestic cattle had been independently derived from wild aurochs populations several times since. From there dairy animals spread to Europe (beginning around 7000 BC but not reaching Britain and Scandinavia until after 4000 BC), and South Asia (7000–5500 BC).


title: Raw milk

text: Pasteurization is widely used to prevent infected milk from entering the food supply. The pasteurization process was developed in 1864 by French scientist Louis Pasteur, who discovered that heating beer and wine was enough to kill most of the bacteria that caused spoilage, preventing these beverages from turning sour. The process achieves this by eliminating pathogenic microbes and lowering microbial numbers to prolong the quality of the beverage.


title: Raw milk

text: After sufficient scientific study led to the development of germ theory, pasteurization was introduced in the United States in the 1890s. This move successfully controlled the spread of highly contagious bacterial diseases including "E. coli", bovine tuberculosis and brucellosis (all thought to be easily transmitted to humans through the drinking of raw milk). In the early days after the scientific discovery of bacteria, there was no product testing to determine whether a farmer's milk was safe or infected, so all milk was treated as potentially contagious. After the first tests were developed, some farmers took steps to prevent their infected animals from being killed and removed from food production, sometimes even falsifying test results to make their animals appear free of infection. Recent advances in the analysis of milk-borne diseases have enabled scientists to track the DNA of the infectious bacteria to the cows on the farms that supplied the raw milk.


title: Raw milk

text: The recognition of many potentially deadly pathogens, such as "E. coli" 0157 H7, "Campylobacter", "Listeria", and "Salmonella", and their possible presence in poorly produced milk products has led to the continuation of pasteurization. The Department of Health and Human Services, Center for Disease Control and Prevention, and other health agencies of the United States strongly recommend that the public do not consume raw milk or raw milk products. Young children, the elderly, people with weakened immune systems, and pregnant women are more susceptible to infections originating in raw milk.


title: Raw milk

text: A number of cheeses are produced with raw milk although local statutes vary regarding what if any health precautions must be followed such as aging cheese for a certain amount of time. A large proportion of the US population eats several different cheeses made with raw milk, including aged gouda.


title: Raw milk

text: The first camembert was made from raw milk, and the (AOC) variety "Camembert de Normandie" (approximately 10% of all camembert production) is required by law to be made only with unpasteurized milk. Many modern cheesemakers, however, use pasteurized milk for reasons of safety, compliance with regulations, or convenience.


title: Raw milk

text: A thick mixture known as syllabub was created by milkmaids squirting milk directly from a cow into a container of cider, beer or other beverage.


title: Raw milk

text: The potential pathogenic bacteria from raw milk, include tuberculosis, diphtheria, typhoid, "Campylobacter", "Listeria", "Brucella", "E. coli", "Salmonella", and streptococcal infections, make it potentially unsafe to consume. Similarly, a recent review authored by the Belgian Federal Agency for the Safety of the Food Chain and experts from Belgian universities and institutions concluded that "raw milk poses a realistic health threat due to a possible contamination with human pathogens. It is therefore strongly recommended that milk should be heated before consumption."


title: Raw milk

text: Before pasteurized milk was adopted in the US, public health officials were concerned with cow milk transmission of bovine tuberculosis to humans, with an estimated 10% of all tuberculosis cases in humans being attributed to milk consumption. Along with specific diseases, officials continue to be concerned about outbreaks. With the use of modern pasteurization and sanitation practices milk accounts for less than 1% of reported outbreaks from food and water consumption. By comparison, raw milk was associated with 25% of all disease outbreaks from food/water during the time before World War II in the U.S. From a public health standpoint, pasteurization has decreased the percentage of milk associated food/water borne outbreaks.


title: Raw milk

text: Outbreaks have occurred in the past from consuming food products made with raw milk. One of the potential pathogens in raw milk, "Listeria monocytogenes", can survive the pasteurization process and contaminate post-pasteurization environments. Milk and dairy products made with that milk then become recontaminated. Consistent contamination persists by bacteria survival in bio-films within the processing systems.


title: Raw milk

text: One food item that has commonly used raw milk in its production in the past is cheese. Several different types of cheeses made with raw milk are consumed by a large portion of the United States population, including soft cheeses. Since Gouda cheese has a 60-day aging period prior to its consumption, it has previously been hypothesized that no bacteria would persist through that time. A review study published in the "Journal of Food Protection" showed that "E. coli" 0157:H7 has the ability to persist through the aging period of Gouda cheese. The study's evidence included three different outbreaks prior to 2013 associated with this specific strain of "E. coli" in Gouda.


title: Raw milk

text: Between 2007 and 2016, there were 144 outbreaks connected to raw milk consumption in the United States. Because raw milk production skips the pasteurization process, the germs that are normally removed remain in the milk product. Exposure to raw milk containing harmful germs poses a threat of infection, resulting from bacteria including "Camplyobacter", "Cryptosporidium", "E. coli", "Listeria", and "Salmonella". Additionally, depending on the severity of infection, there may be further threat to human health. Infection has the potential to induce serious illness such as Guillain-Barré syndrome and Hemolytic Uremic Syndrome (HUS). Because of the vulnerability of developing and degrading immune systems, children, pregnant women, the elderly, and those who are immunocompromised are at a heightened risk of experiencing infection from raw milk consumption.


title: Raw milk

text: One study used mice to evaluate the difference in nutritional values between raw and pasteurized milk. Mice were separated into two groups: a pasteurized milk group and a raw milk group. Each group consisted of breeding pairs. The conclusion of the study measured no significant difference in weights of pasteurized to raw milk consuming mice. Birth weights were measured from each group and showed no significant differences between groups. Overall the study showed no measurable significant difference in nutritional value in growth and fertility of mice.


title: Raw milk

text: "With the exception of an altered organoleptic [flavor] profile, heating (particularly ultra-high temperature and similar treatments) will not substantially change the nutritional value of raw milk or other benefits associated with raw milk consumption."


title: Raw milk

text: Raw milk advocates, such as the Weston A. Price Foundation, say that raw milk can be produced hygienically, and that it has health benefits that are destroyed in the pasteurization process. Research shows only very slight differences in the nutritional values of pasteurized and unpasteurized milk.


title: Raw milk

text: Three studies have found a statistically significant inverse relationship between consumption of raw milk and asthma and allergies. However, all of these studies have been performed in children living on farms and living a farming lifestyle, rather than comparing urban children living typical urban lifestyles and with typical urban exposures on the basis of consumption or nonconsumption of raw milk. Aspects of the overall urban vs. farming environment lifestyle have been suggested as having a role in these differences, and for this reason, the overall phenomenon has been named the "farm effect". A recent scientific review concluded that "most studies alluding to a possible protective effect of raw milk consumption do not contain any objective confirmation of the raw milk's status or a direct comparison with heat-treated milk. Moreover, it seems that the observed increased resistance seems to be rather related to the exposure to a farm environment or to animals than to raw milk consumption." For example, in the largest of these studies, exposure to cows and straw as well as raw milk were associated with lower rates of asthma, and exposure to animal feed storage rooms and manure with lower rates of atopic dermatitis; "the effect on hay fever and atopic sensitization could not be completely explained by the questionnaire items themselves or their diversity."


title: Raw milk

text: Regulation of the commercial distribution of packaged raw milk varies around the world. Some countries have complete bans, but many do not restrict the purchase of raw milk bought directly from the farmer. Raw milk is sometimes distributed through a program, in which the consumer owns a share in the dairy animal or the herd, and therefore can be considered to be consuming milk from their own animal, which is legal. Raw milk is sometimes marketed for animal or pet consumption, or for other uses such as soap making in places where sales for human consumption are prohibited.


title: Raw milk

text: Although milk consumption in Africa is fairly low compared to the rest of the world, in tribes where milk consumption is popular, such as the Maasai tribe, milk is typically consumed unpasteurized.


title: Raw milk

text: In rural areas of Asia where milk consumption is popular, milk is typically unpasteurized. In large cities of Asia, raw milk, especially from water buffalo, is typical. In most countries of Asia, laws prohibiting raw milk are nonexistent or rarely enforced. Milk labelled as "raw" () is available in Japan, but the designation means it is 100% raw whole milk before being pasteurized. Unpasteurized milk is very uncommon in Japan. In Singapore, the sale of raw milk for human consumption is prohibited due to safety concerns outlined by the Singapore Food Agency.


title: Raw milk

text: In India, milk is often drunk raw, although milk supplied in major cities is sometimes pasteurized. Pasteurized or not, milk is often boiled in homes before consumption.


title: Raw milk

text: The European Union requires that raw milk and products made with raw milk must be labeled to indicate this. Under EU hygiene rules, member states can prohibit or restrict the placing on the market of raw milk intended for human consumption. EU member countries are also free to implement their own requirements. Usually special sanitary regulations and frequent quality tests (at least once per month) are mandatory.


title: Raw milk

text: Raw milk cheeses make up about 18 per cent of France's total cheese production, and are considered far superior to cheeses made from pasteurised milk. Many French cuisine traditionalists consider pasteurized cheeses almost a sacrilege. Many traditional French cheeses have solely been made from raw milk for hundreds of years. Unpasteurised cheese in France is the major source of staphylococcal food poisoning.


title: Raw milk

text: In Germany, packaged raw milk may be sold in shops under the name . The raw milk has to be packed before vending, with the necessary information (producer, shelf life, and special warnings) written on the product. The distribution license has stringent quality restrictions; , just 80 farmers in Germany had a license.


title: Raw milk

text: Packed raw milk is sold widely in all health food stores, large supermarkets, gourmet delis and delicatessen sections of department stores. Raw milk is legally sold in the entire country, and the same goes for raw milk cheeses, which are especially sought out and promoted by the health food and slow food movements.


title: Raw milk

text: In the Republic of Ireland, raw milk is legal and its sale and production is regulated by the Department of Agriculture. While raw milk was previously banned in Irish law, since 2015, raw milk production has been regulated in accordance with the European Communities (Food and Feed Hygiene) Regulations (2009). Farmers wishing to produce more than of raw milk for human consumption are required to register with the department's Milk Hygiene Division and consent to random sampling of their products as well as regular inspections of their production facilities. The sale and consumption of raw milk has been discouraged by various food safety experts, including the Food Safety Authority of Ireland.


title: Raw milk

text: Shops are not permitted to sell unpasteurised milk to consumers in Norway, Sweden, Finland, and Denmark. All four countries allow limited "barn door" sales subject to strict controls. , just one distributor in Denmark is licensed to supply restaurants with raw milk from approved farms. Pasteurisation of milk became common practice in Denmark and Sweden in the mid-1880s.


title: Raw milk

text: Raw milk has been available from refrigerated milk vending machines () all over the country since 2010. The milk sold in the machines is subject to stringent regular control.


title: Raw milk

text: , raw milk is also available in shops. The Slovenian National Institute of Public Health advises that consumption of fresh milk from a milk machine that is not heat-treated (boiled) can pose a risk to health.


title: Raw milk

text: About 150 producers of raw milk are listed with the Food Standards Agency in England, Wales and Northern Ireland. They sell raw, or "green top" milk directly to consumers either at the farm, at a farmers' market, or through a delivery service, as it is legal to supply unpasteurised raw milk directly to consumers, but illegal to be sold to a shop. The bottle must display the warning "this product has not been heat-treated and may contain organisms harmful to health", and the milk must conform to higher hygiene standards than dairies producing only pasteurised milk.


title: Raw milk

text: It is an offence to place raw milk or cream on the market for direct consumption in Scotland, following a spate of deaths in 1983.


title: Raw milk

text: The sale of raw milk directly to consumers has been prohibited in Canada under the "Food and Drug Regulations" since 1991.


title: Raw milk

text: Provincial laws also forbid the sale and distribution of raw milk. For instance, Ontario's Health Protection and Promotion Act, subsection 18(1) reads: "No person shall sell, offer for sale, deliver or distribute milk or cream that has not been pasteurized or sterilized in a plant that is licensed under the Milk Act or in a plant outside Ontario that meets the standards for plants licensed under the Milk Act."


title: Raw milk

text: In January 2010, Michael Schmidt was found not guilty on 19 charges relating to the sale of raw milk in the Ontario Court of Justice. On appeal to the Ontario Court of Justice, that decision was overturned. Schmidt was convicted on thirteen counts and imposed fines totaling $9,150 and one year of probation. A subsequent appeal to the Ontario Court of Appeal was dismissed.


title: Raw milk

text: In British Columbia, Alice Jongerden, Michael Schmidt and Gordon Watson—persons involved in the operation of her raw milk dairy—attempted to avoid enforcement of a judgement against them under the Public Health Act by challenging the constitutionality of the legislation, which deems raw milk to be a hazardous product, on the grounds that it violated the Canadian Charter of Rights and Freedoms. This argument, and other defenses invoked by her and defendants in her business, was rejected in 2013 by the Supreme Court of British Columbia, which instead found Schmidt and Watson guilty of civil contempt, and sentenced them to a 3-month suspended sentence imprisonment with a probationary period of 1 year during which "Any repetition of this contempt ... will trigger the imposed sentence imprisonment of 3 months." They were also charged special costs.


title: Raw milk

text: Meanwhile, Canada does permit the sale of raw milk cheeses that are aged over 60 days. In 2009, the province of Quebec modified regulations to allow raw milk cheeses aged less than 60 days provided stringent safeguards are met.


title: Raw milk

text: In the early 20th century, many states within the United States allowed the sale of raw milk that was certified by a "medical milk commission", effectively allowing an alternative of extra inspection for pasteurization. In the present day, most states impose restrictions on raw milk suppliers due to concerns about safety. 43 U.S. states allow the sale of raw milk. Cow shares can be found, and raw milk purchased for animal consumption in many states where retail for human consumption is prohibited. The sale of raw milk cheese is permitted as long as the cheese has been aged for 60 days or more.


title: Raw milk

text: The FDA reports that, in 2002, consuming partially heated raw milk and raw milk products caused 200 Americans to become ill in some manner.


title: Raw milk

text: Many governmental officials and the majority of public health organizations hold to the need for pasteurization. Before pasteurization, many dairies, especially in cities, fed their cattle on low-quality feed, resulting in the production of milk rife with dangerous bacteria. Pasteurizing it was the only way to make it safely drinkable. The Cornell University Food Science Department has compiled data indicating that pathogenic microorganisms are present in between 0.87% and 12.6% of raw milk samples.


title: Raw milk

text: Proponents of raw milk in the US typically argue that pasteurization destroys or damages the nutrients found in milk, and that while pasteurization may kill dangerous bacteria, it also kills off good bacteria claimed to have health benefits not present in pasteurized milk. The United States Food and Drug Administration has stated that this is false, and that pasteurizing milk does not destroy any of its nutritional value.


title: Raw milk

text: Proponents also invoke the benefits of direct-marketing when promoting the sale of raw milk. The ability of the farmer to eliminate the middle-man and sell directly to the consumer allows for greater profitability. Many manufacturers sell small-scale pasteurization equipment, thereby allowing farmers to both bypass the milk processors and sell pasteurized milk directly to the consumer. Additionally, some small U.S. dairies are now beginning to adopt low-temperature vat pasteurization. Advocates of low-temperature vat pasteurization note that it produces a product similar to raw milk in composition.


title: Raw milk

text: Food freedom advocates cite libertarian arguments in claiming a basic civil right of each person to weigh the risks and benefits in choosing the food one eats, including the choice to consume raw milk.


title: Raw milk

text: The sale of raw milk for drinking purposes is illegal in all states and territories in Australia, as is all raw milk cheese. This has been circumvented somewhat by selling raw milk as "bath milk". An exception to the cheese rule has been made recently for two Roquefort cheeses. There is some indication of share owning cows, allowing the "owners" to consume the raw milk, but also evidence that the government is trying to close this loophole.


title: Raw milk

text: On 8 November 2015, four-year-old Apu Khangura died of haemolytic uraemic syndrome, and seven other children became seriously ill, following the consumption of raw milk. In response, the Victorian government created new regulations which require producers to treat raw milk to reduce pathogens, or to make the product unpalatable to taste, such as making it bitter.


title: Raw milk

text: Raw milk for drinking and raw milk products can be made and sold in New Zealand, but are highly regulated to offset the pathogen risk. Producers of raw milk for sale to consumers must be registered. Raw milk must either be collected by the purchaser from the producer's farm or delivered to the purchaser's home.


title: Melioidosis

text: Melioidosis is an infectious disease caused by a gram-negative bacterium called "Burkholderia pseudomallei". Most people exposed to "B. pseudomallei" experience no symptoms; however, those who do experience symptoms have signs and symptoms that range from mild such as fever and skin changes, to severe with pneumonia, abscesses, and septic shock that could cause death. Approximately 10% of people with melioidosis develop symptoms that last longer than two months, termed "chronic melioidosis".


title: Melioidosis

text: Humans are infected with "B. pseudomallei" by contact with contaminated soil or water. The bacteria enter the body through wounds, inhalation, or ingestion. Person-to-person or animal-to-human transmission is extremely rare. The infection is constantly present in Southeast Asia particularly in northeast Thailand and northern Australia. In temperate countries such as Europe and the United States, melioidosis cases are usually imported from countries where melioidosis is endemic. The signs and symptoms of melioidosis resemble tuberculosis and misdiagnosis is common. Diagnosis is usually confirmed by the growth of "B. pseudomallei" from an infected person's blood or other bodily fluid such as pus, sputum, and urine. Those with melioidosis are treated first with an "intensive phase" course of intravenous antibiotics (most commonly ceftazidime) followed by a several-months treatment course of co-trimoxazole. In countries with the advanced healthcare system, approximately 10% of people with melioidosis die from the disease. In less developed countries, the death rate could reach 40%.


title: Melioidosis

text: Efforts to prevent melioidosis include: wearing protective gear while handling contaminated water or soil, practising hand hygiene, drinking boiled water, and avoiding direct contact with soil, water, or heavy rain. There is little evidence in supporting the use of melioidosis prophylaxis in humans. The antibiotic co-trimoxazole is used as a preventative only for individuals at high risk for getting the disease after being exposed to the bacteria in laboratory settings. One study conducted in 2018 determined that the drug could be useful in preventing melioidosis in high-risk renal failure patients undergoing haemodialysis. There is no approved vaccine for melioidosis.


title: Melioidosis

text: Approximately 165,000 people are infected by melioidosis per year, resulting in about 89,000 deaths, based on a mathematical model published in 2016. Diabetes is a major risk factor for melioidosis; over half of melioidosis cases are in people with diabetes. Increased rainfall and severe weather events such as thunderstorms are associated with an increased number of melioidosis cases in endemic areas.


title: Melioidosis

text: Most people exposed to "B. pseudomallei" experience no symptoms. The mean incubation period of acute melioidosis is 9 days (range 1–21 days). Nevertheless, symptoms of melioidosis can appear in 24 hours for those who experienced near drowning in water. Those affected present with symptoms of sepsis (predominantly fever) with or without pneumonia, or localised abscess or other focus of infection. The presence of non-specific signs and symptoms has caused melioidosis to be nicknamed "the great mimicker".


title: Melioidosis

text: Diabetes mellitus is one of the most important risk factors in developing melioidosis. The disease should be considered in anyone who has spent time in endemic areas who develops a fever, pneumonia, or abscesses in their liver, spleen, prostate, or parotid gland. The clinical manifestation of the disease can range from simple skin changes such as abscesses or ulcerations to severe organ problems. The commonest organs affected are liver, spleen, lungs, prostate, and kidneys. Among the most common features are bacteremia (in 40 to 60% of cases), pneumonia (50%), and septic shock (20%).


title: Melioidosis

text: People with only pneumonia may have a prominent cough with sputum and shortness of breath. However, those with septic shock together with pneumonia may have minimal coughing. Results of a chest X-ray can range from diffuse nodular infiltrates in those with septic shock to progressive consolidation located most commonly in the upper lobes for those with pneumonia only. Pleural effusion and empyema are more common for melioidosis affecting lower lobes of the lungs. In 10% of cases, people develop secondary pneumonia caused by other bacteria after the primary infection. In northern Australia, 60% of the infected children presented with only skin lesions, while 20% presented with pneumonia.


title: Melioidosis

text: Depending on the course of infection, other severe manifestations develop. Approximately 1 to 5% of those infected develop inflammation of the brain and brain covering or brain abscess; 14 to 28% develop pyelonephritis, kidney abscess or prostatic abscesses; 0 to 30% develop neck or salivary gland abscesses; 10 to 33% develop liver, spleen, or paraintestinal abscesses; and 4 to 14% develop septic arthritis and osteomyelitis. Rare manifestations include lymph node disease resembling tuberculosis, mediastinal masses, pericardial effusion, mycotic aneurysm, and inflammation of the pancreas. In Australia, up to 20% of infected males develop prostatic abscess which may manifests clinically as pain during urination, difficulty in passing urine, and urinary retention requiring catheterisation. Rectal examination may find enlarged prostate. In Thailand, 30% of the infected children develop parotid abscesses. Encephalomyelitis not only happens in those with risk factors, but can also occur in healthy people without risk factors. Those with melioidosis encephomyelitis tend to have normal computed tomography (CT) scans but increased T2 signal by magnetic resonance imaging (MRI), extending to the brain stem and spinal cord. Clinical signs include: unilateral upper motor neuron limb weakness, cerebellar signs, and cranial nerve palsies (VI, VII nerve palsies and bulbar palsy). Some cases presented with flaccid paralysis alone. In northern Australia, all melioidosis with encephalomyelitis cases had elevated white cells in the cerebrospinal fluid (CSF), mostly mononuclear cells with elevated CSF protein.


title: Melioidosis

text: Chronic melioidosis is usually defined by symptoms lasting greater than two months and occurs in about 10% of patients. Clinical presentations include fever, weight loss, productive cough with or without bloody sputum which may mimic tuberculosis. Additionally, long-standing abscesses at multiple body sites may also present. Tuberculosis should be considered for lymph nodes enlargement at the root of the lung. Additionally, pneumonia caused by melioidosis rarely causes scarring and calcification of the lungs, unlike tuberculosis.


title: Melioidosis

text: The potential for prolonged incubation was recognized in US servicemen involved in the Vietnam War, and was referred to as the "Vietnam time-bomb". Initially, it was thought that the longest period between presumed exposure and clinical presentation is 62 years in a prisoner of war in Burma-Thailand-Malaysia. However, subsequent genotyping of the bacteria isolate from the Vietnam veteran showed that the isolate may not come from Southeast Asia, but from South America. This reinstates another report that put the longest latency period for melioidosis as 29 years. Patients with latent melioidosis may be symptom-free for decades. Less than 5% of all melioidosis cases have activation after a period of latency. Various comorbidities such as diabetes, renal failure, and alcoholism can predispose to reactivation of melioidosis.


title: Melioidosis

text: Melioidosis is caused by gram-negative, motile, saprophytic bacteria named "Burkholderia pseudomallei". The bacteria are usually opportunistic, facultative intracellular pathogens. It is also aerobic and oxidase test positive. A granule at the centre of the bacterium makes it resemble a "safety pin" when Gram stained. The bacteria emit a strong soil smell after 24 to 48 hours of growth in culture, however smelling for the identification of the bacteria is not recommended for routine laboratory practice. One of the factors causing "B. pseudomallei" resistance to various kinds of antibiotics is because of its production of a glycocalyx polysaccharide capsule. It is generally resistant to gentamicin and colistin but sensitive to co-amoxiclav. "B. pseudomallei" is a biosafety level 3 pathogen which requires specialized laboratory handling. In humans and animals, another similar organism named "Burkholderia mallei" is the causative agent of the disease glanders. "B. pseudomallei" can be differentiated from another closely related, but less pathogenic species "B. thailandensis" by its ability to assimilate arabinose. "B. pseudomallei" is highly adaptable to various host environments ranging from inside mycorrhizal fungi spores to amoeba. Its adaptability may give it a survival advantage in the human body.


title: Melioidosis

text: The genome of "B. pseudomallei" consists of two replicons: chromosome 1 encodes housekeeping functions of the bacteria such as cell wall synthesis, mobility, and metabolism; chromosome 2 encodes functions that allow the bacteria to adapt to various environments. Horizontal gene transfer has resulted in highly variable genomes in "B. pseudomallei". Australia has been suggested as the origin for "B. pseudomallei" because of the high genetic variability of the bacteria found in this region. Bacteria that was introduced to Central and South America in the 17th to 19th centuries seem to have a common ancestor from Africa. "B. mallei" is a clone of "B. pseudomallei" that has lost substantial portions of its genome as it adapted to live exclusively in mammals. This makes the "B. mallei" genome much smaller than "B. pseudomallei".


title: Melioidosis

text: "B. pseudomallei" is normally found in soil and surface water, and is most abundant at soil depths of 10 to 90 cm. It has been found in soils, ponds, streams, pools, stagnant water, and rice paddy fields. "B. pseudomallei" can survive in nutrient-poor conditions such as distilled water, desert soil, and nutrient-depleted soil for more than 16 years. It can also survive in antiseptic and detergent solutions, acidic environments (pH 4.5 for 70 days), and in environments at temperatures ranging from 24 °C (75.2 °F) to 32 °C (89.6 °F). However, the bacteria may be killed by the presence of ultraviolet light.


title: Melioidosis

text: Bacteria can enter the body through wounds, inhalation, and ingestion of contaminated soil or water. Person-to-person transmission is extremely rare. Melioidosis is a recognised disease in animals including pigs, cats, dogs, goats, sheep, horses and others. Cattle, water buffalo, and crocodiles are considered to be relatively resistant to melioidosis despite their constant exposure to mud. Birds are also considered resistant to melioidosis although several cases had been reported in Australia and aquatic birds. Transmission from animals to humans is rare.


title: Melioidosis

text: Inadequate chlorination of water supply has been associated with "B. pseudomallei" outbreak in Northern and Western Australia. The were also several cases of where bacteria have also been found in unchlorinated water supply in rural Thailand. Based on the whole genome sequencing of the bacteria, the variety of the bacteria "B. pseudomallei" in Papua New Guinea is narrow due to limited movements of the indigenous people. This findings supports the hypothesis that humans play an important role in bacterial dispersal.


title: Melioidosis

text: "B. pseudomallei" has the ability to infect various types of cells and to evade human immune responses. Bacteria first enter at a break in the skin or mucous membrane and replicate in the epithelial cells. From there, they use flagellar motility to spread and infect various cell types. In the bloodstream, the bacteria can infect both phagocytes and non-phagocytes. "B. pseudomallei" use their flagella to move near host cells, then attach to the cells using various adhesion proteins, including the type IV pilus protein PilA as well as adhesion proteins BoaA and BoaB. Additionally, adhesion of the bacteria partially depends on the presence of the host protein Protease-activated receptor-1 which is present on the surface of endothelial cells, platelets, and monocytes. Once bound, the bacteria enter host cells through endocytosis, ending up inside an endocytic vesicle. As the vesicle acidifies, "B. pseudomallei" uses its Type 3 secretion system (T3SS) to inject effector proteins into the host cell, disrupting the vesicle and allowing the bacteria to escape into the host cytoplasm. Within the host cytoplasm, the bacteria evade being killed by the host autophagy using various T3SS effector proteins. The bacteria replicate in the host cytoplasm.


title: Melioidosis

text: Inside the host cell, the bacteria move by inducing the polymerization of the host actin behind them, propelling the bacteria forward. This actin-mediated motility is accomplished with the autotransporter BimA which interacts with actin at the tail-end of the bacterium. The bacteria that has BimABm allele has higher possibility of causing neurological melioidosis, thus higher chance of death and residual disability to the host when compared to the bacteria that has BimABp variant. Propelled by actin, the bacteria push against the host membrane, creating protrusions that extend into neighbouring cells. These protrusions cause neighboring cells to fuse, leading to the formation of multinucleated giant cells (MNGCs). When MNGCs lyse, they form plaques (a central clear area with a ring of fused cells) that provide shelter for the bacteria for further replication or latent infection. This same process in infected neurons can allow bacteria to travel through nerve roots in the spinal cord and brain, leading to inflammation of the brain and spinal cord. In addition to spreading from cell to cell, the bacteria can also spread through the bloodstream, causing sepsis. The bacteria can survive in antigen-presenting cells and dendritic cells. Thus, these cells act as vehicles that transport the bacteria into the lymphatic system, causing widespread dissemination of the bacteria in the human body.


title: Melioidosis

text: While "B. pseudomallei" can survive in phagocytic cells, these cells can kill "B. pseudomallei" by several mechanisms. Macrophages activated by interferon gamma (IFN) have improved the killing of "B. pseudomallei" via the production of inducible nitric oxide synthase. Acidification of the endosome and degradation of the bacteria is also possible, however, the bacterial capsule and LPS makes "B. pseudomallei" resistant to lysosomal degradation. Once "B. pseudomallei" escapes into the host cytosol it can be recognized by pattern recognition receptors such as NOD-like receptors, triggering the formation of the inflammasome and activation of caspase 1, which induces death of the host cell by pyroptosis and further activation of the immune system. Several systemic host defenses also contribute to the immune response. "B. pseudomallei" triggers both the complement system and coagulation cascade, however the thick bacterial capsule prevent the action of the complement membrane attack complex.


title: Melioidosis

text: Additional elements of the immune system are activated by the host toll-like receptors such as TLR2, TLR4, and TLR5 that recognize the conserved pieces of the bacteria such as LPS and flagella. This activation results in the production of cytokines such as Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18). IL-18 increases IFN production through natural killer cells while IL-1beta reduces the IFN production. These immune molecules drive the recruitment of other immune cells such as neutrophils, dendritic cells, B cells, and T cells to the site of infection. T cells seem to be particularly important for controlling "B. pseudomallei"; T cell numbers are increased in survivors, and low T cell numbers are associated with a high risk of death from melioidosis. Despite this, HIV infection is not a risk factor for melioidosis. Although macrophages show deregulated cytokine responses in individuals with HIV infection, bacterial internalization and intracellular killing are still effective. People infected with "B. pseudomallei" may develop antibodies against the bacteria, and people that live in endemic areas tend to have antibodies in their blood that recognize "B. pseudomallei". However, the effectiveness of these antibodies at preventing melioidosis is unclear.


title: Melioidosis

text: "B. pseudomallei" can remain latent in the human body for up to 29 years until it is reactivated during human immunosuppression or stress response. However, the site of bacteria during latent infection and the mechanism by which they avoid immune recognition for years are both unclear. Amongst mechanisms suggested are: residing in the nucleus of the cell to prevent being digested, entering a stage of slower growth, antibiotic resistance, and genetic adaption to the host environment. Granulomas (containing neutrophils, macrophages, lymphocytes, and multinucleated giant cells) formed at the infection site in melioidosis have been associated with latent infection in humans.


title: Melioidosis

text: Bacterial culture has 60% sensitivity in diagnosing melioidosis. "B. pseudomallei" is never part of human flora. Therefore, any growth of the bacteria is diagnostic of melioidosis. Other samples such as throat, rectal swabs, pus from abscesses, and sputum can also be used for culture. However, culture from CSF is difficult because in one case series, only 29% of the neuromelioidosis cases are culture positive. When bacteria do not grow from people strongly suspected of having melioidosis, repeated cultures should be taken as subsequent cultures can become positive. "B. pseudomallei" can be grown on any blood agar, MacConkey agar, and agar containing antibiotics such as Ashdown's medium (containing gentamicin), and Ashdown's broth (containing colistin) for better isolation of "B. pseudomallei" from other types of bacteria. Agar plates for melioidosis should be incubated at 37 °C (98.6 °F) in air and inspected daily for four days. On the agar plates, "B. pseudomallei" forms creamy, non-haemolytic, colonies after 2 days of incubation. After 4 days of incubation, colonies appear dry and wrinkled. Colonies of "B. pseudomallei" that are grown on Francis medium (a modification of Ashdown medium with gentamicin concentration increased to 8 mg/L and neutral red indicator replaced with 0.2% bromocresol purple) are yellow. For laboratories located outside endemic areas, "Burkholderia cepacia" selective agar can be used if Ashdown's medium is not available. It is important not misinterpret the bacterial growth as "Pseudomonas" or "Bacillus" spp. Other biochemical screening tools can also be used for detecting "B. pseudomallei", including the API 20NE or 20E biochemical kit combined with Gram stain, oxidase test, typical growth characteristics, and resistance to certain antibiotics of the bacteria. API 20NE biochemical kit is 99% sensitive in identifying "B. pseudomallei".


title: Melioidosis

text: Molecular methods such as 16S rDNA sequencing, multiplex polymerase chain reaction (PCR), and real-time PCR can also be used to identify "B. pseudomallei" in culture. Other bacterial genes such as fliC genes encoding flagellin, rpsU gene encoding for ribosomal protein, and TTS genes encoding Type III secretion systems has also been employed for detection. Another method of gene detection namely multiple cross displacement amplification for the bacterial TTS1 gene detection produces results within an hour.


title: Melioidosis

text: General blood tests in people with melioidosis show low white blood cell counts (indicates infection), raised liver enzymes, increased bilirubin levels (indicates liver dysfunction), and raised urea and creatinine levels (indicates kidney dysfunction). Low blood glucose and acidosis predicts a poorer prognosis in those with melioidosis. However, other tests such as C-reactive protein and procalcitonin levels are not reliable in predicting the severity of melioidosis infection.


title: Melioidosis

text: Serological tests such as indirect haemagglutination assay (IHA) have been used to detect the presence of antibodies against "B. pseudomallei". However, different groups of people have widely different levels of antibodies, so interpretation of these tests depends on location. In Australia, less than 5% of people have "B. pseudomallei" antibodies, so the presence of even relatively low amounts of antibody is unusual and could suggest melioidosis. In Thailand, many people have antibodies against "B. pseudomallei" so the diagnosis of melioidosis should not be reliant entirely on the serological tests done in endemic areas. Indirect immunofluorescent test (IFAT) uses either "B. pseudomallei" or "B. thailandensis" antigens to look for the total number of antibodies in human serum. Using IFAT is labour intensive and is not used in large scale investigations.


title: Melioidosis

text: Antigen detect tests allow rapid detection of melioidosis. Examples of antigen detection tests are: latex agglutination test and ELISA. Latex agglutination uses antibodies coated on latex beads to detect "B. pseudomallei" antigens in solid or liquid media, although not all the assays can detect different species of "Burkholderia". Latex agglutination is useful in screening for suspected "B. pseudomallei" colonies. IgG and IgM ELISAs has been used to detect lipopolysaccharide (LPS) antigens of "B. pseudomallei", but plagued with low sensitivity. Commercial ELISA kits for melioidosis no longer available in the market due to low sensitivity to human antibodies detection. Nevertheless, antigen detection tests may be useful in severely ill patients because the bacterial load is high enough for detection. Other methods of antigen detection such as direct immunofluorescence, antibody-sandwich ELISAs, and lateral flow immunoassays using monoclonal antibody.


title: Melioidosis

text: By microscopy, "B. pseudomallei" is seen as gram-negative and rod-shaped, with a bipolar staining similar in appearance to a safety pin. Bacteria can sometimes be seen directly in clinical samples from infected people; however, identification by light microscopy is neither specific nor sensitive. Immunofluorescence microscopy is highly specific for detecting bacteria directly from clinical specimens, but has less than 50% sensitivity.


title: Melioidosis

text: Various imaging modalities can also help with the diagnosis of melioidosis. In acute melioidosis with the spreading of the bacteria through the bloodstream, the chest X-ray shows multifocal nodular lesions. It may also show merging nodules or cavitations. For those with acute melioidosis without the spread to the bloodstream, chest x-ray most commonly shows upper lobe consolidation or cavitations. In chronic melioidosis, the slowly progressing of upper lobe consolidation of the lungs resembles tuberculosis. For abscesses located in other parts of the body apart from the lungs, especially in the liver and spleen, CT scan has higher sensitivity when compared with an ultrasound scan. In liver and splenic abscesses, an ultrasound scan shows "target-like" lesions while CT scan shows "honeycomb sign" (abscess with loculations separated by thin septa) in liver abscesses. For melioidosis involving the brain, MRI have higher sensitivity than a CT scan in diagnosing the lesion. MRI shows ring-enhancing lesions for brain melioidosis.


title: Melioidosis

text: Melioidosis is a notifiable disease in Australia which enables the country to monitor disease burden and contain outbreaks. On the other hand, melioidosis is only a notifiable condition in Thailand since June 2016. However, until recently, the official notification system in Thailand has significantly underestimated the incidence of culture-positive melioidosis and its mortality. Nevertheless, Australia also embarked on awareness campaigns to increase the community's understanding of the disease. In the United Kingdom, where reporting by laboratories is mandatory, 41.3% of cases imported since 2010 were not notified. In the United States, lab workers can handle clinical specimens of "B. pseudomallei" under BSL-2 conditions, while mass production of such organisms requires BSL-3 precautions. On the other hand, in other endemic areas where the "B. pseudomallei" samples were handled less stringently, there has been no confirmed laboratory-acquired infection reported. This phenomenon may show that the risk of infection with "B. pseudomallei" is less than a typical biohazard type 3 agent. There are also several cases of hospital-acquired infection of melioidosis. Therefore, healthcare providers are recommended to practice hand hygiene and universal precautions.


title: Melioidosis

text: Large-scale water chlorination has been successful at reducing "B. pseudomallei" in the water in Australia. In middle to low-income countries, water should be boiled before consumption. In high income countries, water could be treated with ultraviolet light for those at risk of contracting melioidosis. Those who are at high risk of contact with the bacteria should wear protective gear (such as boots and gloves) during work. Those staying in endemic areas should avoid direct contact with soil, and outdoor exposure to heavy rain or dust clouds. Bottled water or boiled water are preferred as drinking water. A study conducted from 2014 to 2018, however showed no significant differences on whether behavioural changes can reduce the risk of contracting melioidosis. Modification of behavioural changes or more frequent interventions may be needed to ensure a definite reduction in risk of getting melioidosis.


title: Melioidosis

text: Administering cotrimoxazole three times a week throughout a wet season for dialysis patients has no obvious benefit of preventing melioidosis. Besides, high cost and side effects of this drug limits its use to only those with high risk of getting melioidosis. After exposure to "B. pseudomallei" (particularly following a laboratory accident, penetrating injuries, exposure of mouth and eyes to contaminated materials or aerosols), treatment with antibiotics is only given when in highly selected individuals after weighing the risk of adverse effects of the drugs against the benefits from contracting melioidosis. Cotrimoxazole can be used in this context. Alternatively, co-amoxiclav and doxycycline can be used for those who are intolerant to co-trimoxazole. Low-risk individuals would receive frequent monitoring instead.


title: Melioidosis

text: Several vaccine candidates have been tested in animal models. Nevertheless, no vaccine candidates have been tried in humans. Major hurdles of the vaccines are limited efficacy in animal models, establishing the best method of vaccine administration in humans and logistical and financial issues in establishing human trials in endemic areas.


title: Melioidosis

text: The treatment of melioidosis is divided into two stages: an intravenous intensive phase and an eradication phase to prevent recurrence. The choice of antibiotics depends upon the susceptibility of the bacteria to various antibiotics. "B. pesudomallei" are generally susceptible to ceftazidime, meropenem, imipenem, and co-amoxiclav. These drugs generally kill bacteria. "B. pseudomallei" is also susceptible to doyxcycline, chloramphenicol, and co-trimoxazole. These drugs generally inhibit the growth of the bacteria. However, the bacteria are resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporin, gentamicin, streptomycin, tobramycin, macrolides, and polymyxins. On the other hand, 86% of the "B. pseudomallei" isolates from the region of Sarawak, Malaysia are susceptible to gentamicin and this has not been found elsewhere in other parts of the world.


title: Melioidosis

text: Prior to 1989, the standard treatment for acute melioidosis was a three-drug combination of chloramphenicol, co-trimoxazole and doxycycline; this regimen is associated with a mortality rate of 80% and is no longer used unless no other alternatives are available. All three drugs are bacteriostatic (they stop the bacterium from growing, but do not kill it) and the action of co-trimoxazole antagonizes both chloramphenicol and doxycycline.


title: Melioidosis

text: Intravenous ceftazidime is the current drug of choice for treatment of acute melioidosis and should be administered for at least 10 to 14 days. Meropenem, imipenem and the cefoperazone-sulbactam combination (Sulperazone) are also effective. Intravenous amoxicillin-clavulanate (co-amoxiclav) may be used if none of the above four drugs is available; co-amoxiclav prevents death from melioidosis as well as ceftazidime. Co-amoxiclav is also used if patient has allergy towards sulfonamide, unable to tolerate co-trimaxazole, in pregnant patients or in children. High dose of co-amoxiclav (20 mg/kg for amoxicillin and 5 mg/kg for clavulanate) is recommended to prevent treatment failures. Intravenous antibiotics are given for a minimum of 10 to 14 days. The median fever clearance time in melioidosis is 9 days. The treatment duration is in accordance with Darwin melioidosis treatment guidelines where there is low rate of recrudescence and relapse.


title: Melioidosis

text: Meropenem is the preferred antibiotic therapy for neurological melioidosis and those with septic shock admitted into intensive care units. Co-trimoxazole is recommended in addition to ceftazidime for neurological melioidosis, osteomyelitis, septic arthritis, skin and gastrointestinal infection, and deeply seated abscess. For deep-seated infections such as abscesses of internal organs, osteomyelitis, septic arthritis, and neurological melioidosis, the duration of antibiotics given should be longer (up to 4 to 8 weeks). The time taken for the fever to be resolved can be more than 10 days in those with deep-seated infection. According to the 2020 Revised Royal Darwin Hospital Guideline, the dosage for intravenous ceftazidime is 2g 6-hourly in adults (50 mg/kg up to 2g in children less than 15 years old). The dosage for meropenem is 1g 8-hourly in adults (25 mg/kg up to 1g in children). Acquired resistance to ceftazidime, carbapenems, and co-amoxiclav is rare in the intensive phase but resistance to cotrimoxazole during eradication therapy is technically difficult to assess. There are no differences between using cefoperazone/sulbactam or ceftazidime to treat melioidosis as both shows similar death rates and disease progression following treatment. However, data are lacking to recommend cefoperazone/sulbactam usage. For those with kidney impairment, the dosage of ceftazidime, meropenem, and co-trimoxazole should be lowered. Once the clinical condition improved, meropenem can be switched back to ceftazidime.


title: Melioidosis

text: Following the treatment of the acute disease, eradication treatment with co-trimoxazole is the drug of choice and should be used for 3 months (12 weeks) as all-cause mortality was lower in 12 weeks group when compared to those receiving treatment for 20 weeks. For those with neurological melioidosis and osteomyelitis, drugs should be given for more than 6 months. Co-amoxiclav and doxycycline are drugs of second choice. Co-trimoxazole should not be used in those with glucose-6-phosphate dehydrogenase deficiency as it can cause haemolytic anemia. However, in Thailand, usage of co-trimoxazole does not accompany G6PD screening. Other side effects such as rash, hyperkalemia, renal dysfunction, and gastrointestinal symptoms should prompt the reduction of co-trimoxazole doses. Chloramphenicol is no longer routinely recommended for this purpose. Co-amoxiclav is an alternative for patients unable to take co-trimoxazole and doxycycline (e.g. pregnant women and children under the age of 12), but is not as effective and has a higher relapse rate. Single-agent treatment with fluoroquinolone (e.g., ciprofloxacin) or doxycycline for the oral eradication phase is ineffective.


title: Melioidosis

text: In Australia, co-trimoxazole is used with children and pregnant mothers after the first 12 weeks of pregnancy. Meanwhile, in Thailand, co-amoxiclav is the drug of choice for children and pregnant women. "B. pseudomallei" rarely acquires resistance when co-amoxiclav is used. The dosing regimen for co-trimoxazole (trimethoprim/sulfamethoxazole) in eradication phase is 6/30 mg/kg, up to maximum 240/1200 mg in children, 240/1200 mg in adults weighing 40 to 60 kg, and 320/1600 mg in adults weighing more than 60 kg, taken orally every 12 hours. In both Thailand and Australia, co-trimoxazole is taken together with folic acid (0.1 mg/kg up to 5 mg in children). There are also cases where melioidosis is successfully treated with co-trimoxazole for 3 months without going through intensive therapy provided that there is only skin manifestations without the involvement of internal organs or sepsis. Resistance to cotrimoxazole is rare in Asia. Besides that, it is difficult to determine the resistance reliably because resistance to cotrimoxazole is defined when minimum inhibitory concentration (MIC) of more than 4 mg/L is required to completely inhibit the growth of 80% of the bacteria (80% inhibition point). Interpretation of 80% inhibition point is subjective and prone to human error. In 2021, European Committee on Antimicrobial Susceptibility Testing (EUCAST) released a new guideline on interpreting the susceptibility of "B pseudomallei" towards various antibiotics on disc susceptibility testing. The new guideline includes "S" for susceptible organism, "I" for susceptible organism only after increased exposure (when dosage or concentration of the drug increases) and "R" for resistant organism.


title: Melioidosis

text: Surgical drainage is indicated for single, large abscesses in the liver, muscle, and prostate. However, for multiple abscesses in the liver, spleen, and kidney, surgical drainage may not be possible or necessary. For septic arthritis, arthrotomy washout and drainage are required. Surgical debridement may be necessary. For those with mycotic aneurysm, urgent surgery is required for prosthetic vascular grafts. Lifelong therapy with co-trimoxazole may be needed for those with prosthetic vascular grafts according to a review of case reports in 2005. Other abscesses rarely need to be drained because most resolve with antibiotic treatment. Prostate abscess may require routine imaging. Antibiotics treatment for prostatic abscess may be enough except for abscesses more than 10 to 15 mm where surgical drainage is required.


title: Melioidosis

text: Several immunomodulating therapies are suggested to boost the human body immune function against the bacteria because the pathogenesis of melioidosis is thought to be contributed by defects in neutrophils. The Royal Darwin Hospital 2014 guidelines recommended granulocyte colony-stimulating factor (G-CSF) as immunomodulating therapy for those with septic shock at 300 ug daily as soon as the bacteriological laboratory flag the culture as possibly "Burkholderia pseudomallei". The main contraindication of starting (G-CSF) is a heart event. The G-CSF is continued for ten days depends on clinical response or a contraindication develops such as white cell count greater than >50,000 X106/litre.


title: Melioidosis

text: Anti-PDI (programmed cell death) agents could be useful in melioidosis treatment especially for those with septic shock. This is because "Burkholderia pseudomallei" bacteria increases the expression of PDI-1 that regulates and inhibits the formation of T-cells that are essential for fighting against melioidosis.


title: Melioidosis

text: In well-resourced settings, where the disease can be detected and treated early, the risk of death is 10%. In resource-poor settings, the risk of death from the disease is more than 40%.


title: Melioidosis

text: Recurrent melioidosis can occur either due to re-infection or relapse after the completion of eradication therapy. Re-infection is due to a new strain of "B. pseudomallei" bacteria. Meanwhile, relapse is due to failure to clear infections after the eradication therapy. Recurrent melioidosis is rare since 2014 due to improved antibiotic therapy and prolongation of the intensive phase of therapy as evident in Darwin Prospective Melioidosis Study. On the other hand, recrudescence are those who present with symptoms during the eradication therapy. Recrudescence rates may be improved by ensuring adherence to a full course of eradication therapy e.g. by reducing self-discharge against medical advice.


title: Melioidosis

text: Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and cancer can worsen the long-term survival and disability of those who recover from infection. One of the complications of melioidosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs), partial flaccid paraparesis (muscle weakness of both legs), or foot drop. For those with previous melioidosis-associated bone and joint infections, complications such as sinus tract infection, bone and joint deformities with limited range of motion can occur.


title: Melioidosis

text: Melioidosis is an understudied disease that remains endemic in developing countries. In 2015, the International Melioidosis Society was formed to raise awareness of the disease. In 2016, a statistical model was developed which predicted that the number is 165,000 cases per year with 138,000 of those occurring in East and South Asia and the Pacific. In approximately half of those cases (54% or 89,000), people will die. Under-reporting is a common problem as only 1,300 cases were reported worldwide since 2010, which is less than 1% of the projected incidence based on the modelling. Lack of laboratory diagnostic capabilities and lack of disease awareness amongst health care providers also causes under diagnosis. Even if bacterial cultures show positive result for "B. pesudomallei", they can be discarded as contaminants especially in laboratories in non-endemic areas. In 2015, it was estimated that the yearly disability-adjusted life year (DALY) was 84.3 per 100,000 people. As of 2022, melioidosis is not included in the WHO list of neglected tropical diseases.


title: Melioidosis

text: Melioidosis is endemic in parts of southeast Asia (including Thailand, Laos, Singapore, Brunei, Malaysia, Myanmar and Vietnam), southern China, Taiwan northern Australia. India, and South America. Since 1991, a total of 583 cases were reported in India. Most Indian cases are located in Karnataka and Tamil Nadu. Fifty-one cases of melioidosis were reported in Bangladesh from 1961–2017. Nonetheless, lack of awareness and resources gives rise to under diagnosis of the disease in the country. The true burden of melioidosis in Africa and Middle East remain unknown due to low amount of data. Several melioidosis cases were reported over the years. Although 24 African countries and three Middle Eastern countries predicted to be endemic with melioidosis, however not a single case was reported from these specific countries. In the United States, two historical cases (1950 and 1971) and four recent cases (2010, 2011, 2013, 2020) have been reported amongst people that did not travel overseas. Despite extensive investigations, the source of melioidosis was never confirmed. One possible explanation is that importation of medicinal plant products or exotic reptiles could have resulted in the introduction of melioidosis in the United States. In 2021, there was a melioidosis outbreak in several states in the United States due to usage of contaminated aromatherapy spray imported from India. There are also cases of infection through imported tropical fishes in home aquariums.


title: Melioidosis

text: Melioidosis is found in all age groups. For Australia and Thailand, the median age of infection is at 50 years; 5 to 10% of the patients are under 15 years. The single most important risk factor for developing melioidosis is diabetes mellitus, followed by hazardous alcohol use, chronic kidney disease, and chronic lung disease. More than 50% of people with melioidosis have diabetes; diabetics have a 12-fold increased risk of contracting melioidosis. Diabetes decreases the ability of macrophages to fight the bacteria and reduced the T helper cell production. Excessive release of Tumor necrosis factor alpha and Interleukin 12 by mononuclear cells increases the risk of septic shock. Other risk factors include thalassaemia, occupational exposure (e.g. rice paddy farmers), recreational exposure to soil, water, being male, age greater than 45 years, and prolonged steroid use/immunosuppression. However, 8% of children and 20% of adults with melioidosis have no risk factors. HIV infection does not appear to predispose to melioidosis, although several other co-infections have been reported. Infant cases have been reported possibly due to mother-to-child transmission, community-acquired infection, or healthcare-associated infection. Those who are well may also be infected with "B. pseudomallei". For example, 25% of children started producing antibodies against "B. pseudomallei" between 6 months to 4 years of staying in endemic areas although they did not experience any melioidosis symptoms; suggesting they were exposed to it over this time. This means that many people without symptoms will test positive in serology tests in endemic areas. In Thailand, the seropositivity rate exceeds 50%, while in Australia the seropositivity rate is only 5%. The disease is clearly associated with increased rainfall, with the number of cases rising following increased precipitation. Severe rainfall increases the concentration of the bacteria in the topsoil, thus increasing thus of transmitting the bacteria through the air. A recent CDC Advisory indicated that the recent detection of the organism in the environment in Mississippi following the occurrence of two indigenous cases of melioidosis, confirms that parts of the southern USA should now be regarded as melioidosis-endemic.


title: Melioidosis

text: Pathologist Alfred Whitmore and his assistant Krishnaswami first reported melioidosis among beggars and morphine addicts at autopsy in Rangoon, present-day Myanmar, in a report published in 1912. Whitmore was able to grow the organism in culture and its showed similarity with "B. mallei", another bacteria that was known causing glanders in animals. Therefore, he named the new organism "Bacillus pseudomallei". He did no further work on the organism. Arthur Conan Doyle may have read Whitmore's report before writing a short story that involved the fictitious tropical disease "Tapanuli fever" in a Sherlock Holmes story titled "The Adventure of the Dying Detective" published in 1913. In the same year, melioidosis outbreak occurred inside the Institute for Medical Research (IMR), Kuala Lumpur, Malaya after its laboratory animals such as guinea pigs and rabbits were infected. William Fletcher and Ambrose Thomas Stanton, doctors who worked at the IMR, were the next ones to study the organism. They were unable identify the organism that caused the outbreak. It was only in 1917, when Fletcher isolated an organism similar to Whitmore's bacillus from a Tamil rubber estate worker, the presence of the new species of bacteria was confirmed. The term "melioidosis" was first coined in 1921. The name melioidosis is derived from the Greek "melis" (μηλις) meaning "a distemper of asses" with the suffixes -oid meaning "similar to" and -osis meaning "a condition", that is, a condition similar to glanders. "B pseudomallei" is similar in clinical presentation and genome make-up with "B. mallei" but is distinguished from it due to epidemiological and zoonotic characteristics.


title: Melioidosis

text: The first human case of melioidosis in South Asia was reported in Sri Lanka in 1927. In 1932, Thomas and Fletcher collected 83 cases of melioidosis from literature. In this case series, there were only two survivals. Since then, more case series of melioidosis were reported. Thomas and Fletcher also pioneered the use of serological methods in diagnosing the disease. Thomas and Fletcher incorrectly believed that melioidosis infection came from human contact with rodents. However, observations on the disease noted that humans usually got it after exposure to mud or contaminated water. Besides, the organism was never grown from rats. This led to a search of the bacteria in the environment. In 1936, the first animal (pig) case of melioidosis in Africa was reported in Madagascar. In 1937, water was first identified as the habitat of "B. pseudomallei". The first case of Australian melioidosis was described in an outbreak in sheep in 1949 at North Queensland. This was followed by the first case of human melioidosis at Townsville in 1950. Initially, the discovery of melioidosis in Australia had led to a debate on when and how the disease spread from Southeast Asia to a new distant environment. However, this hypothesis was later disproved in 2017 when whole genome sequencing of "B. pseudomallei" over 30 countries collected over 79 years suggested Australia as the early reservoir for melioidosis. In 1955, first case of local human melioidosis was reported in Thailand. During the Vietnam War from 1967 to 1973, 343 American soldiers were reported with melioidosis, with about 50 cases transmitted through inhalation. An outbreak of melioidosis at the Paris Zoo in the 1970s (known as "L'affaire du jardin des plantes") was thought to have originated from an imported panda or horses from Iran. It is unclear how imported melioidosis is able to persist in a completely new environment. Eventually, the outbreak terminated by itself after a period of time. It was only during the 1980s, Infectious Disease Association of Thailand started took notice of this disease. First conference on melioidosis was held in 1985 in Thailand. It was during this meeting that collaboration between Sappasitprasong Hospital, Thailand, and Wellcome-Mahido-Oxford Tropical Medicine Research Programme was established. Such collaboration made Thailand a world leader in clinical and epidemiology research on melioidosis.


title: Melioidosis

text: In 1989, several studies conducted in Thailand demonstrated ceftazidime as an effective antibiotic against melioidosis. Ceftazidime had been shown to reduce the risk of death of melioidosis from 74% to 37%. In 1990, a non-virulent 'arabinose-positive B. pseudomallei' was found by Vanaporn Wuthiekanun. The organism was later reclassified into a new species called "B. thailandensis". This species has become a useful tool in the laboratory for the studies of the pathogenesis of "B. pseudomallei". "B. pseudomallei" was previously classified as part of the genus "Pseudomonas". In 1992, the pathogen was formally named "B. pseudomallei". In 1994, First International Symposium on melioidosis was held in Kuala Lumpur where 80 delegates attended. Papers were presented and later published as a book. Subsequent congresses were held in Thailand, Australia, and Singapore once every three years. In 2002, "B. pseudomallei" was classified as a "Category B agent". In 2004, the complete genome of "B. pseudomallei" was published. In 2012, "B pseudomallei" was classified as a "Tier 1 select agent" by the U.S. Centers for Disease Control. In 2014, co-trimoxazole was established as the only oral eradication therapy rather than combination therapy of co-trimoxazole with doxycycline. In 2016, a statistical model was developed to predict the occurrence of global melioidosis per year.


title: Melioidosis

text: Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. Another similar bacterium, "Burkholderia mallei" was used by the Germans in World War I to infect livestock shipped to Allied countries. Deliberate infection of human prisoners of war and animals using "B. mallei" were carried out in China's Pingfang District by the Japanese during World War II. The Soviet Union reportedly used "B. mallei" during the Soviet–Afghan War in 1982 and 1984. "B. pseudomallei", like "B. mallei", was studied by both the US and Soviet Union as a potential biological warfare agent, but never weaponized. Other countries such as Iran, Iraq, North Korea, and Syria may have investigated the properties of "B. pseudomallei" for biological weapons. The bacterium is readily available in the environment. It can also be aerosolized and transmitted via inhalation. However, the "B. pseudomallei" has never been used in biological warfare. The actual risk of the deliberate release of "B. pseudomallei" or "B. mallei" is unknown.


title: Weber State University

text: Weber State University (pronounced ) is a public university in Ogden, Utah. It was founded in 1889 as Weber Stake Academy. It is accredited by the Northwest Commission on Colleges and Universities.


title: Weber State University

text: Weber State University was founded by the Church of Jesus Christ of Latter-day Saints as the Weber Stake Academy in 1889. "Weber" comes from the name of the county where the university is located. Weber County was named after John Henry Weber, an early fur trader. The university opened for students in 1889 with 98 students enrolled for classes The first principal of Weber Stake Academy was Louis F. Moench; he served from 1889 to 1892 and again from 1894 to 1902. In the latter year, Moench was succeeded as principal by David O. McKay, who served in that position until 1908. From 1914 to 1917, James L. Barker was the principal of the Weber Stake Academy.


title: Weber State University

text: In the early 20th century, the school underwent multiple name changes: Weber Stake Academy from its founding in 1889, Weber Academy in 1902, Weber Normal College in 1918, and Weber College in 1922. By the late 1920s, however, the college was in financial difficulty, and the Church of Jesus Christ of Latter-day Saints faced four choices—transfer the college to a partnership of the city of Ogden and Weber County, transfer it to the University of Utah as a branch campus, transfer it to the state of Utah as a junior college, or shut it down. In 1931, the Utah Legislature passed a law providing for the acquisition of Weber College and Snow College from the Church of Jesus Christ of Latter-day Saints.


title: Weber State University

text: In 1933, Weber College became a state-supported junior college. In 1954, the college moved from its downtown location in Ogden to a spacious and scenic area in the southeast bench area of the city. The school became Weber State College in 1962, and in 1964 became a four-year college. It was a charter member of the Big Sky Conference The first graduate program (accounting), was added and it gained university status on


title: Weber State University

text: Weber State University has developed into a major state undergraduate institution serving northern Utah and areas beyond, including American and international students.