''Giardia duodenalis'', also known as ''Giardia intestinalis'' and ''Giardia lamblia'', is a
flagellate
A flagellate is a cell or organism with one or more whip-like appendages called flagella. The word ''flagellate'' also describes a particular construction (or level of organization) characteristic of many prokaryotes and eukaryotes and the ...
d
parasitic
Parasitism is a close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The ent ...
protozoa
Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...
n microorganism of the genus ''
Giardia
''Giardia'' ( or ) is a genus of anaerobic flagellated protozoan parasites of the phylum Metamonada that colonise and reproduce in the small intestines of several vertebrates, causing the disease giardiasis. Their life cycle alternates be ...
'' that colonizes the
small intestine
The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...
, causing a diarrheal condition known as
giardiasis
Giardiasis is a parasitic disease caused by the protist enteropathogen ''Giardia duodenalis'' (also known as ''G. lamblia'' and ''G. intestinalis''), especially common in children and travellers. Infected individuals experience steatorrhea, a typ ...
.
The parasite attaches to the
intestinal epithelium
The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorptio ...
by a ventral disc (''syn''.
adhesive disc or sucker), and
reproduce
Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. There are two forms of reproduction: asexual and sexual.
In asexual reprod ...
s via
binary fission
Binary may refer to:
Science and technology Mathematics
* Binary number, a representation of numbers using only two values (0 and 1) for each digit
* Binary function, a function that takes two arguments
* Binary operation, a mathematical o ...
.
''G. duodenalis'' is a non-invasive parasite, that does not spread to other parts of the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
, but remains confined to the
lumen of the small intestine. The parasite exists in two forms;
trophozoites and
cysts
A cyst is a closed Wikt:sac, sac, having a distinct Cell envelope, envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac ...
. The microorganism can undergo encystation, transforming into a dormant
cyst
A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubb ...
that enables it to survive outside of its
host
A host is a person responsible for guests at an event or for providing hospitality during it.
Host may also refer to:
Places
* Host, Pennsylvania, a village in Berks County
* Host Island, in the Wilhelm Archipelago, Antarctica
People
* ...
.
''Giardia''
trophozoite
A trophozoite (G. ''trope'', nourishment + ''zoon'', animal) is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing ''Plasmodium falciparum'' and those of the ''Giardia'' group. The complementary form of the t ...
s are
anaerobic
Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to:
*Adhesive#Anaerobic, Anaerobic ad ...
, and absorb their nutrients from the intestinal lumen. If the organism is
stained, its characteristic pattern resembles the familiar "
smiley face" symbol.
Chief pathways of human infection include ingestion of
untreated drinking water (which is the most common method of transmission for this parasite),
food, soil contaminated with human feces, and
sewage
Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater that is produced by a community of people. It is typically transported through a sewerage, sewer system. Sewage consists of wastewater discharged fro ...
, a phenomenon particularly common in many
developing countries
A developing country is a sovereign state with a less-developed Secondary sector of the economy, industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. ...
.
Contamination of natural waters also occurs in
watersheds where intensive
grazing
In agriculture, grazing is a method of animal husbandry whereby domestic livestock are allowed outdoors to free range (roam around) and consume wild vegetations in order to feed conversion ratio, convert the otherwise indigestible (by human diges ...
occurs.
''Giardia'' infections occur worldwide. It is the most commonly identified intestinal parasite among children in day-care centers, hikers and
immunocompromised
Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
patients. About 20,000 cases per year in the United States are reported.
Almost half of those infected with giardiasis remain asymptomatic. For those who do experience symptoms, they usually appear 1 to 2 weeks after infection. Common symptoms include abdominal pain, nausea, and bloating, along with large, watery, foul-smelling, and greasy stools. Due to frequent loose stools, individuals with giardiasis often experience dehydration.
It has also been shown that ''G. intestinalis'' damages the intestinal epithelium, which directly affects nutrient absorption.
In severe cases, giardiasis can lead to chronic diarrhea, chronic fatigue syndrome and cognitive impairment in children.
Life cycle

''G. duodenalis'' takes on two morphologically distinct forms during its lifecycle.
Trophozoites are the replicative stage of the parasite, characterized by a pear-shaped,
motile
Motility is the ability of an organism to move independently using metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components.
Motility is observed in animals, mi ...
,
flagellate
A flagellate is a cell or organism with one or more whip-like appendages called flagella. The word ''flagellate'' also describes a particular construction (or level of organization) characteristic of many prokaryotes and eukaryotes and the ...
d cell that survives only in the small intestine of the host.
The trophozoites do not penetrate host cells, but rather attaches to the intestinal epithelium cells to establish an infection. A cyst is the environmentally stable stage of the parasite, that facilitates transmission between hosts.
The infection process in the host begins with the ingestion of cysts, which pass through the stomach into the first part of small intestine, or the
duodenum
The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption.
The duodenum precedes the jejunum and ileum and is the shortest p ...
. Exposure to
digestive enzymes
Digestive enzymes take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes ...
and an acidic
pH triggers excystation, where the cysts release trophozoites.
Trophozoites swim through the intestinal mucus until they eventually adhere to the
intestinal epithelium
The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorptio ...
using their
ventral disc.
Adhered trophozoites can then feed, divide by
binary fission
Binary may refer to:
Science and technology Mathematics
* Binary number, a representation of numbers using only two values (0 and 1) for each digit
* Binary function, a function that takes two arguments
* Binary operation, a mathematical o ...
and cause the disease. Trophozoites cause structural and functional damage to the host epithelial cells, impairing the intestine's ability to absorb nutrients effectively.
Some trophozoites differentiate back into cysts under specific conditions, such as high organism density.
As the trophozoites travel through the intestinal lumen to the
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the Digestion, digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces befor ...
, the alkaline environment and the presence of
pancreatic proteases trigger the encystation. Trophozoites develop into cysts through encystation, which involves specialized vesicles (ESVs) that facilitate the formation of the cyst wall.
Cysts and trophozoites pass through the host's
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the Digestion, digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces befor ...
and are shed in the feces.
Trophozoites cannot survive outside of the host, whereas cysts can remain viable in the external environment for several months.
The cysts remain
dormant until ingested by a host animal. When a new potential host ingests water or food contaminated with this feces, the cysts gain entry to the gastrointestinal tract of the new host, repeating the cycle.
Structure
The trophozoite has an elaborate structure with two nuclei and four pairs of
flagella
A flagellum (; : flagella) (Latin for 'whip' or 'scourge') is a hair-like appendage that protrudes from certain plant and animal sperm cells, from fungal spores ( zoospores), and from a wide range of microorganisms to provide motility. Many pr ...
which allow it to swim within the intestinal lumen of the host. It also has an adhesive disk on its
ventral
Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...
surface that is associated with the parasite's attachment to the intestinal epithelium. The adhesive disk is composed of
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
, and is found only in ''Giardia''. The parasite lacks
Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...
and
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
but has
mitosome
A mitosome (also called a ''crypton'' in early literature) is a mitochondrion-related organelle (MRO) found in a variety of parasitic unicellular eukaryotes, such as members of the supergroup Excavata. The mitosome was first discovered in 1999 in ...
s, which probably evolved from mitochondria.
The mitosome is a double-membraned organelle, that lacks the enzymatic components required for classic mitochondrial functions, such as ATP synthesis and lipid metabolism. However, they do contain certain mitochondrial genes associated with iron-sulfur complex biosynthesis, which suggests that this organism likely lost its mitochondria during evolution.
The cyst contains four nuclei,
axonemes, median bodies as well as the rigid cyst wall. Additionally, the cysts contain fragments of the adhesive disc within the cytoplasm.
The two-layered cyst wall protects the parasite against different environmental conditions such as chemical treatments. The metabolic activity of the cyst is significantly lower compared to that of the trophozoites, which allows the parasite to survive for longer periods in harsh conditions, such as in cold environments.
Prevalence and epidemiology
''G. duodenalis'' causes an infection called giardiasis. This disease is the cause of both endemic and epidemic disease worldwide and is the most frequently identified intestinal parasite in the United States and Canada. An infected individual can excrete between 1 million and 1 billion cysts daily, and the
infectious dose The concept of a minimal infective dose (MID), also known as the infectious dose, has traditionally been used for infectious microorganisms that contaminate foods. MID was defined as the number of microorganisms ingested (the dose) from which a pat ...
can be as low as 10 cysts. This makes ''Giardia'' extremely infectious.
It is estimated to infect over 280 million people world every year
resulting in over 500,000 deaths. The most affected demographic is children 0 to 4 years of age. Globally ''G. duodenalis'' is the most commonly identified protozoal intestinal parasite.
Giardia has common seasonal patterns in the distribution of infection rates with highest peaks in the late summer to early fall.
The cyst can survive for weeks to months in cold water,
so the parasite can be present in contaminated wells and water systems, especially in stagnant water sources, such as naturally occurring ponds, storm-water storage systems, and even clean-looking mountain streams. Cysts can also be found on contaminated surfaces, soil and food. They may also occur in city reservoirs and persist after water treatment, as the cysts are resistant to conventional water-treatment methods, such as
chlorination and
ozonolysis
In organic chemistry, ozonolysis is an organic reaction where the Saturated and unsaturated compounds, unsaturated bonds are Bond cleavage, cleaved with ozone (). Multiple carbon–carbon bond are replaced by carbonyl () groups, such as aldehydes ...
.
Zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
transmission is also possible, but is less frequent. ''Giardia'' infection is a concern for people camping in the wilderness or swimming in contaminated streams or lakes, especially the artificial lakes formed by
beaver
Beavers (genus ''Castor'') are large, semiaquatic rodents of the Northern Hemisphere. There are two existing species: the North American beaver (''Castor canadensis'') and the Eurasian beaver (''C. fiber''). Beavers are the second-large ...
dams (hence the popular name for giardiasis, "beaver fever").
In addition to waterborne sources, ''Giardia'' infections are more commonly found in children compared to adults, this is believed to be due to
fecal-oral transmission of the cysts. For example, in developed countries it affects approximately 2% of adults and 8% of children. In developing countries the prevalence rates reach 15% to 20% in children under 10 years old.
Thus, there is a significant variation in infection rates based on geographical area.
Those who work with children are also at risk of being infected, as are family members of infected individuals. 7% of children aged 1 to 3 years and 11% of infants and toddlers tested for admission to day-care centers were found to be infected.
Not all ''Giardia'' infections are symptomatic, and many people can unknowingly serve as carriers of the parasite. Re-infection and chronic infections of the parasite can occur.
Geographical prevalence
''G. duodenalis'' is the most widespread intestinal parasite affecting humans. The parasite ''Giardia duodenalis'' can be found all over the world, in both developing and industrialized nations. However, human infections are most common in
tropical
The tropics are the regions of Earth surrounding the equator, where the sun may shine directly overhead. This contrasts with the temperate or polar regions of Earth, where the Sun can never be directly overhead. This is because of Earth's ax ...
and
subtropical
The subtropical zones or subtropics are geographical zone, geographical and Köppen climate classification, climate zones immediately to the Northern Hemisphere, north and Southern Hemisphere, south of the tropics. Geographically part of the Ge ...
climates.
''Giardia duodenalis'' is common around the world because the parasite resides in bodies of water; typically rivers, lakes, and recreational swimming pools. Giardiasis is more prevalent in
developing countries
A developing country is a sovereign state with a less-developed Secondary sector of the economy, industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. ...
, where the sanitation and overall hygiene is poorer compared to
developed countries
A developed country, or advanced country, is a sovereign state that has a high quality of life, developed economy, and advanced technological infrastructure relative to other less industrialized nations. Most commonly, the criteria for eval ...
.
In developed nations, giardiasis has a prevalence of 2–5%, whereas in developing nations it is significantly higher, ranging from 20% to 30%.
In the United States, it has been discovered that a majority of whom are infected by the ''Giardia duodenalis'' parasite tend to reside in more urban areas, and, patients who are infected are more likely to live in the Southern United States.
Ecology
''Giardia'' infects humans, but is also one of the most common parasites infecting cats, dogs, and birds. Mammalian hosts also include dozens of species,
[ ] including
cattle
Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
,
sheep
Sheep (: sheep) or domestic sheep (''Ovis aries'') are a domesticated, ruminant mammal typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus '' Ovis'', in everyday usage it almost always refers to d ...
,
and
goat
The goat or domestic goat (''Capra hircus'') is a species of Caprinae, goat-antelope that is mostly kept as livestock. It was domesticated from the wild goat (''C. aegagrus'') of Southwest Asia and Eastern Europe. The goat is a member of the ...
s.
[ ]
Cats can be cured easily, and 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
chinchilla
Chinchilla refers to either of two species ('' Chinchilla chinchilla'' and '' Chinchilla lanigera'') of crepuscular rodents of the parvorder Caviomorpha, and are native to the Andes mountains in South America. They live in colonies called "her ...
s, 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
kennel
A kennel is a structure or shelter for dogs. Used in the plural, ''the kennels'', the term means any building, collection of buildings or a property in which dogs are housed, maintained, and (though not in all cases) bred. A kennel can be made o ...
s. 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 presumptively treated together. Kennels and 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
quarantine
A quarantine is a restriction on the movement of people, animals, and goods which is intended to prevent the spread of disease or pests. It is often used in connection to disease and illness, preventing the movement of those who may have bee ...
of infected dogs for at least 20 days and careful management and maintenance of a clean water supply.
Cell biology
''G. duodenalis'' trophozoites are pear-shaped cells, 10 to 20
μm
The micrometre (Commonwealth English as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American English), also commonly known by the non-SI term micron, is a unit of length in the International System ...
long, 7 to 10 μm across, and 2 to 4 μm thick.
They are motile by way of four pairs of flagella
A flagellum (; : flagella) (Latin for 'whip' or 'scourge') is a hair-like appendage that protrudes from certain plant and animal sperm cells, from fungal spores ( zoospores), and from a wide range of microorganisms to provide motility. Many pr ...
, which propel the trophozoites through the intestine.[ Notably, each ''G. duodenalis'' cell has two nuclei, both of which actively transcribe genes.][ Adjacent to the nucleus, ''G. duodenalis'' cells have an ]endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
that extends through much of the cell. Trophozoites about to differentiate into cysts also contain prominent vesicles termed encystation-specific vesicles that disappear once cyst wall construction begins.[ Unlike most other eukaryotes, ''G. duodenalis'' cells contain no visible ]mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
, but instead contains a substantially reduced metabolic organelle known as a mitosome
A mitosome (also called a ''crypton'' in early literature) is a mitochondrion-related organelle (MRO) found in a variety of parasitic unicellular eukaryotes, such as members of the supergroup Excavata. The mitosome was first discovered in 1999 in ...
.[ Additionally, cells appear to contain no ]Golgi bodies
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...
, and instead the secretory system consists entirely of the endoplasmic reticulum and numerous vesicles dispersed throughout the cell, termed peripheral vesicles.[ Peripheral vesicles are responsible both for taking up extracellular nutrients, and expelling waste outside the cell.] Each cell also contains a pair of rigid structures called median bodies which make up part of the ''G. lamblia'' cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
.[ Trophozoites adhere to host epithelial cells via a specialized disk-shaped organelle called the ventral disk.][
Cysts are oval-shaped cells slightly smaller than trophozoites.][ They lack flagella, and are covered by a smooth, clear cyst wall.][ Each cyst contains four nuclei and fragments of the ventral disc.][
]
Metabolism
''G. duodenalis'' primarily generates its energy by breaking down glucose
Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
via glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...
, as well as the arginine deiminase pathway. It is unable to synthesize nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
s on its own, instead salvaging them from its host. Synthesis of iron–sulfur cluster
Iron–sulfur clusters are molecular ensembles of iron and sulfide. They are most often discussed in the context of the biological role for iron–sulfur proteins, which are pervasive. Many Fe–S clusters are known in the area of organometall ...
s is done in a double-membrane-bound compartment called the mitosome, which is likely a remnant of mitochondria.[ Each cell contains 25 to 100 mitosomes divided into two categories - peripheral mitosomes, which are scattered throughout the cell, and central mitosomes, which gather at the center of the cell for unknown reasons.] As in mitochondria, proteins with a certain peptide signal sequence are trafficked to and imported into the mitosome. Unlike mitochondria, mitosomes have no genome of their own. All mitosomal genes are encoded by the ''Giardia'' nuclear genome.[
]
Genetics
''Giardia'' and the other diplomonad
The diplomonads (Greek for "two units") are a group of flagellates, most of which are parasitic. They include ''Giardia duodenalis'', which causes giardiasis in humans. They are placed among the metamonads, and appear to be particularly close ...
s are unique in their possession of two cell nuclei
The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoc ...
that are similar in appearance, DNA content, transcription, and time of replication. ''Giardia'' is a polyploid
Polyploidy is a condition in which the biological cell, cells of an organism have more than two paired sets of (Homologous chromosome, homologous) chromosomes. Most species whose cells have Cell nucleus, nuclei (eukaryotes) are diploid, meaning ...
organism, with at least four, and perhaps eight or more, copies of each of five chromosomes per organism. The genome has been sequenced and was published in 2007, although the sequence contains several gaps. The sequence is about 12 million base pairs and contains about 5000 protein-coding genes. The GC-content
In molecular biology and genetics, GC-content (or guanine-cytosine content) is the percentage of nitrogenous bases in a DNA or RNA molecule that are either guanine (G) or cytosine (C). This measure indicates the proportion of G and C bases out of ...
is 46%. Trophozoites have a ploidy
Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Here ''sets of chromosomes'' refers to the number of maternal and paternal chromosome copies, ...
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. Eight genotype assemblages of ''G. duodenalis'' have been recognized to date (A-H). Genotyping of ''G. duodenalis'' isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main assemblages that undeniably infect human subjects.
Immunology
Infections with ''Giardia'' are self-limited in immunocompetent individuals, while people with immunodeficiency disorders may develop chronic giardiasis. During the infection different mechanisms from the