Giardia lamblia is a
flagellateFlagellates are organisms with one or more whip-like organelles called flagella. Some cells in animals may be flagellate, for instance the spermatozoa of most phyla. Flowering plants do not produce flagellate cells, but ferns, mosses, green algae, some gymnosperms and other closely related plants...
d
protozoaProtozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
n parasite that colonizes and reproduces in the small intestine, causing
giardiasisGiardiasis or beaver fever in humans is a diarrheal infection of the small intestine by a single-celled organism Giardia lamblia. Giardiasis occurs worldwide with a prevalence of 20–30% in developing countries. In the U.S., 20,000 cases are reported to the CDC annually, but the true annual...
. The giardia parasite attaches to the
epitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
by a ventral adhesive disc, and reproduces via binary fission. Giardiasis does not spread via the bloodstream, nor does it spread to other parts of the
gastro-intestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, but remains confined to the
lumenA lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of the small intestine. Giardia trophozoites absorb their nutrients from the lumen of the small intestine, and are anaerobes. If the organism is split and stained, it has a very characteristic pattern that resembles a familiar "smiley face" symbol. Chief pathways of human infection include ingestion of untreated sewage, a phenomenon particularly common in many developing countries; contamination of natural waters also occurs in watersheds where intensive grazing occurs.
Hosts
Giardia infects humans, but is also one of the most common parasites infecting cats, dogs and birds. Mammalian hosts also include cows,
beaverThe beaver is a primarily nocturnal, large, semi-aquatic rodent. Castor includes two extant species, North American Beaver and Eurasian Beaver . Beavers are known for building dams, canals, and lodges . They are the second-largest rodent in the world...
s,
deerDeer are the ruminant mammals forming the family Cervidae. Species in the Cervidae family include white-tailed deer, elk, moose, red deer, reindeer, fallow deer, roe deer and chital. Male deer of all species and female reindeer grow and shed new antlers each year...
, and sheep.
Transmission
Giardia infection can occur through ingestion of dormant
microbial cystA microbial cyst is a resting or dormant stage of a microorganism, usually a bacterium or a protist, that helps the organism to survive in unfavorable environmental conditions. It can be thought of as a state of suspended animation in which the metabolic processes of the cell are slowed down and...
s in contaminated water, food, or by the faecal-oral route (through poor hygiene practices). The cyst can survive for weeks to months in cold water, and therefore can be present in contaminated wells and water systems, especially stagnant water sources such as naturally occurring ponds, storm water storage systems, and even clean-looking mountain streams. They may also occur in city reservoirs and persist after water treatment, as the cysts are resistant to conventional water treatment methods such as
chlorinationChlorination is the process of adding the element chlorine to water as a method of water purification to make it fit for human consumption as drinking water...
and
ozonolysisOzonolysis is the cleavage of an alkene or alkyne with ozone to form organic compounds in which the multiple carbon–carbon bond has been replaced by a double bond to oxygen...
. Zoonotic transmission is also possible, and therefore Giardia infection is a concern for people camping in the wilderness or swimming in contaminated streams or lakes, especially the artificial lakes formed by
beaverThe beaver is a primarily nocturnal, large, semi-aquatic rodent. Castor includes two extant species, North American Beaver and Eurasian Beaver . Beavers are known for building dams, canals, and lodges . They are the second-largest rodent in the world...
dams (hence the popular name for giardiasis, "Beaver Fever").
In addition to waterborne sources, fecal-oral transmission can also occur, for example in day care centers, where children may have poor hygiene practices. Those who work with children are also at risk of being infected, as are family members of infected individuals. Not all Giardia infections are symptomatic, and many people can unknowingly serve as carriers of the parasite.
Life cycle
The life cycle begins with a noninfective cyst being excreted with the feces of an infected individual. The cyst is hardy, providing protection from various degrees of heat and cold,
desiccationDesiccation is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic substance that induces or sustains such a state in its local vicinity in a moderately sealed container.-Science:...
, and infection from other organisms. A distinguishing characteristic of the cyst is four nuclei and a retracted cytoplasm. Once ingested by a host, the trophozoite emerges to an active state of feeding and motility.
After the feeding stage, the trophozoite undergoes asexual replication through longitudinal binary fission. The resulting trophozoites and cysts then pass through the digestive system in the faeces. While the trophozoites may be found in the faeces, only the cysts are capable of surviving outside of the host.
Distinguishing features of the trophozoites are large karyosomes and lack of peripheral
chromatinChromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
, giving the two nuclei a halo appearance. Cysts are distinguished by a retracted cytoplasm. This protozoan lacks mitochondria, although the discovery of the presence of mitochodrial remnants organelles in one recent study "indicate that Giardia is not primitively amitochondrial and that it has retained a functional organelle derived from the original mitochondrial endosymbiont" This organelle is now termed a
mitosomeA mitosome is an organelle found in some unicellular eukaryotic organisms. The mitosome has only recently been found and named, and its function has not yet been well characterized. It was termed a 'crypton' by one group, but that name is no longer in use....
.
Intracellular metabolism and biochemistry
Giardia relies on
glucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
as its major energy source and breaks glucose down into ethanol, acetate and carbon dioxide. However, it can also use
arginineArginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
as an energy source. Giardia possesses unique biochemical pathways that suggest that it diverged from other eukaryotes at an early stage in
evolutionEvolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
.
B vitamins and bile salts, as well as glucose, are necessary for Giardia to survive, and a low-carbohydrate diet was shown in mice to reduce the number of Giardia organisms present.
Manifestation of infection
Nomenclature of Giardia species is difficult, as humans and other animals appear to have morphologically identical parasites.
Colonization of the gut results in inflammation and villous atrophy, reducing the gut's absorptive capability. In humans, infection is symptomatic only about 50% of the time, and protocol for treating asymptomatic individuals is controversial. Symptoms of infection include (in order of frequency) diarrhea,
malaiseMalaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, excessive gas (often flatulence or a foul or sulphuric-tasting belch, which has been known to be so nauseating in taste that it can cause the infected person to vomit), steatorrhoea (pale, foul smelling, greasy stools), epigastric pain, bloating, nausea, diminished interest in food, possible (but rare) vomiting which is often violent, and weight loss. Pus, mucus and blood are occasionally present in the stool. It usually causes "explosive diarrhea" and while unpleasant, is not fatal. In healthy individuals, the condition is usually self-limiting, although the infection can be prolonged in patients who are immunocompromised, or who have decreased gastric acid secretion.
People with recurring Giardia infections, particularly those with a lack of the
Immunoglobulin AImmunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....
antibody, may develop chronic disease.
Lactase deficiencyLactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...
may develop in an infection with Giardia, however this usually does not persist for more than a few weeks, and a full recovery is the norm.
Some studies have shown that giardiasis should be considered as a cause of
vitamin B12 deficiencyVitamin B12 deficiency or hypocobalaminemia is a low blood level of vitamin B12, it can cause permanent damage to nervous tissue as a long term effect. Vitamin B12 was discovered from its relationship to the disease pernicious anemia, which is an autoimmune disease that destroys parietal cells in...
, this a result of the problems caused within the intestinal absorption system.
Prevention
Treatment of drinking water for Giardia is ordinarily indicated in wilderness regions in North America, although at least four researchers disagree with this statement, including Robert W. Derlet, a professor at the University of California-Davis School of Medicine, Timothy P. Welch and Thomas R. Welsh of Tulane Medical School and the Children's Hospital of Cincinnati respectively, and Robert Rockwell, a widely quoted writer who is an engineer by training.
Boiling suspect water for one minute is the surest method to make water safe to drink and kill disease-causing microorganisms like Giardia lamblia if in doubt about whether water is infected with the Giardia parasite.
Treatment and diagnosis
Giardia lamblia infection in humans is frequently misdiagnosed. Accurate diagnosis requires an antigen test or, if that is unavailable, an ova and parasite examination of stool. Multiple stool examinations are recommended, since the cysts and trophozoites are not shed consistently. Given the difficult nature of testing to find the infection, including many false negatives, some patients should be treated on the basis of empirical evidence; treating based on symptoms.
Human infection is conventionally treated with
metronidazoleMetronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....
,
tinidazoleTinidazole is an anti-parasitic drug used against protozoan infections. It is widely known throughout Europe and the developing world as treatment for a variety of amoebic and parasitic infections...
or
nitazoxanideNitazoxanide, also known by the brand names Alinia and Annita is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent.Nitazoxanide is a light yellow...
. Although Metronidazole is the current first-line therapy, it is mutagenic in bacteria and carcinogenic in mice, so should be avoided during pregnancy. It has not directly been linked to causing cancer in humans, only in other mammals, therefore appears safe. One of the most common alternative treatments is berberine sulfate (found in Oregon grape root,
goldensealGoldenseal is a perennial herb in the buttercup family Ranunculaceae, native to southeastern Canada and the northeastern United States. It may be distinguished by its thick, yellow knotted rootstock. The stem is purplish and hairy above ground and yellow below ground where it connects to the...
,
yellowrootThe Yellowroot is the only member of the genus Xanthorhiza, and one of very few genera in the family Ranunculaceae with a woody stem...
, and various other plants).
BerberineBerberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary...
has been shown to have an
antimicrobialAn anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
and an
antipyreticAntipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature...
effect. Berberine compounds cause
uterineThe word uterine can refer to different meanings:* relating to or near the uterus or womb* having the same mother, but different fathers, see matrilineality...
stimulation, and so should be avoided in pregnancy. Continuously high dosing of berberine may lead to
bradycardiaBradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
and
hypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
in some individuals.
| Drug |
Treatment duration |
Possible Side Effects |
| Metronidazole Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....
|
5–7 days |
Metallic taste; nausea; vomiting; dizziness; headache; disulfiram-likeDisulfiram is a drug discovered in the 1920s and used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are Antabuse and Antabus manufactured by Odyssey Pharmaceuticals...
effect; neutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
|
TinidazoleTinidazole is an anti-parasitic drug used against protozoan infections. It is widely known throughout Europe and the developing world as treatment for a variety of amoebic and parasitic infections...
|
Single dose |
Metallic taste; nausea; vomiting; belching; dizziness; headache; disulfiram-likeDisulfiram is a drug discovered in the 1920s and used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are Antabuse and Antabus manufactured by Odyssey Pharmaceuticals...
effect |
| Nitazoxanide Nitazoxanide, also known by the brand names Alinia and Annita is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent.Nitazoxanide is a light yellow...
|
3 days |
Abdominal pain; diarrhea; vomiting; headache; yellow-green discolouration of urine |
AlbendazoleAlbendazole, marketed as Albenza, Eskazole, Zentel and Andazol, is a member of the benzimidazole compounds used as a drug indicated for the treatment of a variety of worm infestations. Although this use is widespread in the United States, the U.S. Food and Drug Administration has not approved...
|
5 days |
Dizziness; headache; fever; nausea; vomiting; temporary hair loss |
Table adapted from Huang, White.
Treatment in animals
Cats can be cured easily, lambs usually simply lose weight, but in calves, the parasites can be fatal and often are not responsive to antibiotics or electrolytes. Carriers among calves can also be asymptomatic. This parasite is deadly for chinchillas, so extra care must be taken by providing them with safe water. Dogs have a high infection rate, as 30% of the population under one year old are known to be infected in kennels. The infection is more prevalent in puppies than in adult dogs. Infected dogs can be isolated and treated, or the entire pack at a kennel can be treated together regardless. Kennels should also be then cleaned with bleach or other cleaning disinfectants. The grass areas used for exercise should be considered contaminated for at least one month after dogs show signs of infection, as cysts can survive in the environment for long periods of time. Prevention can be achieved by
quarantineQuarantine is compulsory isolation, typically to contain the spread of something considered dangerous, often but not always disease. The word comes from the Italian quarantena, meaning forty-day period....
of infected dogs for at least 20 days and careful management and maintenance of a clean water supply.
Microscopy
Under a normal compound light
microscopeA microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...
, Giardia often looks like a "clown face," with two nuclei outlined by adhesive discs above dark median bodies that form the "mouth." Cysts are oval, have four nuclei, and have clearly visible
axostyleAn axostyle is a sheet of microtubules found in certain microbial eukaryotes. It arises from the bases of the flagella, sometimes projecting beyond the end of the cell, and is often flexible or contractile, and so may be involved in movement and provides support for the cell...
s.
In spite of the common belief that all Eukaryotes have mitochondria, Giardia is one of the few that lack these organelles.
Research
Giardia alternates between two different forms — a hardy, dormant
cystA microbial cyst is a resting or dormant stage of a microorganism, usually a bacterium or a protist, that helps the organism to survive in unfavorable environmental conditions. It can be thought of as a state of suspended animation in which the metabolic processes of the cell are slowed down and...
that contaminates water or food and an active, disease-causing form that emerges after the parasite is ingested.
National Institute of General Medical SciencesThe National Institute of General Medical Sciences is a part of the National Institutes of Health that primarily supports research that lays the foundation for advances in disease diagnosis, treatment and prevention...
grantee Dr. Frances Gillin of the
University of California, San DiegoThe University of California, San Diego, commonly known as UCSD or UC San Diego, is a public research university located in the La Jolla neighborhood of San Diego, California, United States...
and her colleagues cultivated the entire life cycle of this parasite in the laboratory, and identified biochemical cues in the host's digestive system which trigger Giardias life cycle transformations. They also uncovered several ways in which the parasite evades the defences of the infected organism. One of these is by altering the
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s on its surface, which confounds the ability of the infected animal's
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to detect and combat the parasite (called
antigenic variationAntigenic variation refers to the mechanism by which an infectious organism such as a protozoan, bacterium or virus alters its surface proteins in order to evade a host immune response. Immune evasion is particularly important for organisms that target long-lived hosts, repeatedly infect a single...
). Gillin's work reveals why Giardia infections are extremely persistent and prone to recur. In addition, these insights into Giardias biology and survival techniques may enable scientists to develop better strategies to understand, prevent, and treat Giardia infections.
In December 2008, Nature published an article showing the discovery of an RNA Interference mechanism that allows Giardia to switch VSPs (Variant-Specific Surface Proteins) to avoid host immune response. The discovery was made by the team working at the Biochemistry and Molecular Biology Laboratory, School of Medicine, Catholic University of Cordoba, Argentina, led by Dr. Hugo Lujan.
Genomics
Giardia and the other
diplomonadThe diplomonads are a group of flagellates, most of which are parasitic. They include most notably Giardia lamblia, which causes giardiasis in humans...
s are unique in their possession of two
nucleiIn cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
that are similar in appearance, DNA content,
transcriptionTranscription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
and time of replication. There are five chromosomes per the haploid genome
The genome has been sequenced and was published in 2007, although the sequence contains several gaps. The sequence is approximately 12 million base pairs and contains approximately 5000 protein coding genes. The GC content is 46%. Trophozoites have a
ploidyPloidy is the number of sets of chromosomes in a biological cell.Human sex cells have one complete set of chromosomes from the male or female parent. Sex cells, also called gametes, combine to produce somatic cells. Somatic cells, therefore, have twice as many chromosomes. The haploid number is...
of four and the ploidy of cysts is eight, which in turn raises the question of how Giardia maintains homogeneity between the chromosomes of the same and opposite nuclei. Modern sequencing technologies have been used to resequence different strains.
Giardia has been assumed to be primitively asexual and with no means of transferring DNA between nuclei. These assumptions make it very difficult to explain the remarkably low level of allelic heterozygosity (< 0.01%) in the genome isolate, WB. However, all these assumptions are now in doubt with the identification of meiotic genes, evidence for recombination among isolates and the evidence for exchange of genetic material between nuclei during the process of encystation.
Seven genotypes have been recognised to date (A-G). Of these B is the most widespread. Only types A and B have been shown to be infectious to humans.
History
The trophozoite form of Giardia was first observed in 1681 by Antonie van Leeuwenhoek in his own diarrhea stools. The organism was again observed and described in greater detail by
Vilém Dušan LamblVilém Dušan Lambl was a Czech physician from Letina, Kreis Pilsen, Bohemia.Lambl had a keen interest in the field of linguistics, particularly Slavic languages...
in 1859, who thought the organism belonged to the genus Cercomonas and proposed the name Cercomonas intestinalis. His name is still sometimes attached to the genus or the species infecting humans. Thereafter, some have named the genus after him while others have named the species of the human form after him Giardia lamblia. In 1879, Grassi discovered a rodent parasite now known to be a Giardia species Dimorphus muris apparently unaware of Lambl's earlier description. In 1882 and 1883, Johann Künstler described an organism in tadpoles (possibly Giardia agilis) that he named Giardia, this being the first time Giardia was used as a genus name. The genus was chosen to honour Professor
Alfred Mathieu GiardAlfred Mathieu Giard was a French zoologist born in Valenciennes on August 8, 1846. He was a professor at the Sorbonne, at École centrale de Lille and served as director of the marine laboratory in Wimereux ....
of Paris.
Raphaël BlanchardRaphaël Blanchard was a French doctor and entomologist.-Works:*Les moustiques. Histoire naturelle et médicale Paris, F.R. de Rudeval, 1905*with Paul Bert Éléments de zoologie G...
, in 1888, proposed the name Lamblia intestinalis, after Lambl. Stiles changed it to Giardia duodenalis in 1902 and to Giardia lamblia in 1915. The same year (1915), Kofoid and Christiansen wrote "The generic name Lamblia Blanchard 1888 should give way to Giardia Kunstler 1882 on ground of priority…" (the epithet being intestinalis) and used Giardia enterica in 1920.
The naming of the species still causes controversy. While initially species names were based on the host of origin leading to over forty species. In 1922 Simon, using morphologic criteria to distinguish between Giardia lamblia and Giardia muris accepted the name Giardia lamblia for the human species. Filice in 1922 further revised the genus when he published a detailed morphologic description of the genus Giardia and proposed that three species names be used on the basis of the morphology of the median body: Giardia agilis, Giardia duodenalis and Giardia muris.
The names for the human parasite Giardia duodenalis, Giardia lamblia and Giardia intestinalis are all in common current use despite the potential for confusion that this has created.
Van Leeuwenhoek's observations were recreated, using a single lensed microscope of the kind he used, by British microbiologist
Brian J. FordBrian J. Ford is an independent research biologist, author, and lecturer, who publishes on scientific issues for the general public...
who showed how clearly one could view Giardia through a primitive microscope.
In 1998, a highly publicised Giardia and
CryptosporidiumCryptosporidium is a protozoan that can cause gastro-intestinal illness with diarrhea in humans.Cryptosporidium is the organism most commonly isolated in HIV positive patients presenting with diarrhea...
outbreak was reported in
Sydney, AustraliaThe 1998 Sydney water crisis involved the supposed contamination of Sydney's main water supply, the Warragamba Dam, by the microscopic pathogens cryptosporidium and giardia between July and September 1998....
, but it was found to be due to mis-measurement of the concentrations of microbes in the water supply.
A 2004 outbreak in
BergenBergen is the second largest city in Norway with a population of as of , . Bergen is the administrative centre of Hordaland county. Greater Bergen or Bergen Metropolitan Area as defined by Statistics Norway, has a population of as of , ....
(
NorwayNorway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...
) hastened work on adding UV treatment to the water facilities.
In October 2007, Giardia was found in the water supply for parts of
OsloOslo is a municipality, as well as the capital and most populous city in Norway. As a municipality , it was established on 1 January 1838. Founded around 1048 by King Harald III of Norway, the city was largely destroyed by fire in 1624. The city was moved under the reign of Denmark–Norway's King...
, prompting authorities to advise the public to boil drinking water; but subsequent test showed levels of contamination too low to pose a threat, so this advice has since been cancelled.
In 2008, Giardia was identified as one of the causes of the
dysenteryDysentery is an inflammatory disorder of the intestine, especially of the colon, that results in severe diarrhea containing mucus and/or blood in the faeces with fever and abdominal pain. If left untreated, dysentery can be fatal.There are differences between dysentery and normal bloody diarrhoea...
afflicting
CrusaderThe Crusades were a series of religious wars, blessed by the Pope and the Catholic Church with the main goal of restoring Christian access to the holy places in and near Jerusalem...
s in
PalestinePalestine is a conventional name, among others, used to describe the geographic region between the Mediterranean Sea and the Jordan River, and various adjoining lands....
in the 12th and 13th centuries.
External links