Trichuriasis
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Trichuriasis, also known as whipworm infection, is an infection by the
parasitic worm Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as sc ...
''
Trichuris trichiura ''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intes ...
'' (whipworm). If infection is only with a few worms, there are often no symptoms. In those who are infected with many worms, there may be
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...
,
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
and
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
. The diarrhea sometimes contains blood. Infections in children may cause poor intellectual and physical development. Low red blood cell levels may occur due to loss of blood. The disease is usually spread when people eat food or drink water that contains the eggs of these worms. This may occur when contaminated vegetables are not fully cleaned or cooked. Often these eggs are in the soil in areas where people defecate outside and where untreated human
feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...
is used as
fertilizer A fertilizer (American English) or fertiliser (British English; see spelling differences) is any material of natural or synthetic origin that is applied to soil or to plant tissues to supply plant nutrients. Fertilizers may be distinct from ...
. These eggs originate from the feces of infected people. Young children playing in such soil and putting their hands in their mouths also become infected easily. The worms live in the
large bowel The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being rem ...
and are about four centimetres in length. Whipworm is diagnosed by seeing the eggs when examining the stool with a
microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisi ...
. Eggs are barrel-shaped. Trichuriasis belongs to the group of soil-transmitted helminthiases. Prevention is by properly cooking food and
hand washing Hand washing (or handwashing), also known as hand hygiene, is the act of cleaning one's hands with soap or handwash and water to remove viruses/bacteria/microorganisms, dirt, grease, or other harmful and unwanted substances stuck to the hands ...
before cooking. Other measures include improving access to
sanitation Sanitation refers to public health conditions related to clean drinking water and treatment and disposal of human excreta and sewage. Preventing human contact with feces is part of sanitation, as is hand washing with soap. Sanitation syste ...
such as ensuring use of functional and clean
toilets A toilet is a piece of sanitary hardware that collects human urine and feces, and sometimes toilet paper, usually for disposal. Flush toilets use water, while dry or non-flush toilets do not. They can be designed for a sitting position popul ...
and access to clean water. In areas of the world where the infections are common, often entire groups of people will be treated all at once and on a regular basis. Treatment is with three days of the medication:
albendazole Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, ho ...
,
mebendazole Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disea ...
or
ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat i ...
. People often become infected again after treatment. Whipworm infection affected about 464 million in 2015. It is most common in
tropical countries The tropics are the regions of Earth surrounding the Equator. They are defined in latitude by the Tropic of Cancer in the Northern Hemisphere at N and the Tropic of Capricorn in the Southern Hemisphere at S. The tropics are also referred to ...
. Those infected with whipworm often also have
hookworm Hookworms are intestinal, blood-feeding, parasitic roundworms that cause types of infection known as helminthiases. Hookworm infection is found in many parts of the world, and is common in areas with poor access to adequate water, sanitation, ...
and
ascariasis Ascariasis is a disease caused by the parasitic roundworm ''Ascaris lumbricoides''. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may i ...
infections. These diseases have a large effect on the economy of many countries. Work is ongoing to develop a
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
against the disease. Trichuriasis is classified as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bac ...
.


Signs and symptoms

Light infestations (<100 worms) frequently have no symptoms. Heavier infestations, especially in small children, can present gastrointestinal problems including abdominal pain and distension, bloody or mucus-filled diarrhea, and tenesmus (feeling of incomplete defecation, generally accompanied by involuntary straining). Mechanical damage to the intestinal mucosa may occur, as well as toxic or inflammatory damage to the intestines of the host. While appendicitis may be brought on by damage and edema of the adjacent tissue, if there are large numbers of worms or larvae present, it has been suggested that the embedding of the worms into the ileocecal region may also make the host susceptible to bacterial infection. A severe infection with high numbers of embedded worms in the rectum leads to edema, which can cause rectal prolapse, although this is typically only seen in small children. The prolapsed, inflamed and edematous rectal tissue may even show visible worms. Physical growth delay,
weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...
,
nutritional deficiencies Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
, and
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
(due to long-standing blood loss) are also characteristic of infection, and these symptoms are more prevalent and severe in children. It does not commonly cause
eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic sy ...
.
Coinfection Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with he ...
of ''T. trichiura'' with other parasites is common and with larger worm burdens can cause both exacerbation of dangerous trichuriasis symptoms such as massive gastrointestinal bleeding (shown to be especially dramatic with coinfection with ''
Salmonella typhi ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of '' Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includi ...
'') and exacerbation of symptoms and pathogenesis of the other parasitic infection (as is typical with coinfection with ''
Schistosoma mansoni A paired couple of ''Schistosoma mansoni''. ''Schistosoma mansoni'' is a water-borne parasite of humans, and belongs to the group of blood flukes ''Schistosoma'' is a genus of trematodes, commonly known as blood flukes. They are parasiti ...
'', in which higher worm burden and liver egg burden is common). Parasitic coinfection with HIV/AIDS, tuberculosis, and malaria is also common, especially in
sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
, and helminth coinfection adversely affects the natural history and progression of HIV/AIDS, tuberculosis, and malaria and can increase clinical malaria severity. In a study performed in Senegal, infections of soil-transmitted helminths like ''T. trichiura'' (as well as schistosome infections independently) showed enhanced risk and increased the incidence of malaria. Heavy infestations may have bloody
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
. Long-standing
blood loss Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...
may lead to
iron-deficiency anemia Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
.
Vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...
deficiency may also result due to infection.


Cause

Trichuriasis is caused by a parasitic worm also known as a
helminth Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as ...
called ''
Trichuris trichiura ''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intes ...
''. It belongs to the genus '' Trichuris'', formerly known as ''Trichocephalus'', meaning hair head, which would be a more accurate name; however the generic name is now ''Trichuris'', which means hair tail (implying that the posterior end of the worm is the attenuated section). Infections by parasitic worms are known as
helminthiasis Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are ...
.


Reservoir

Humans are the main, but not the only reservoir for ''T. trichiura''. Recent research verified by the application of molecular techniques (PCR) that dogs are a reservoir for ''T. trichiura'', as well as ''T. vulpis''.


Vector

Non-biting cyclorrhaphan flies (''Musca domestica'', ''M. sorbens'', ''Chrysomya rufifacies'', ''C. bezziana'', ''Lucina cuprina'', ''Calliphora vicina'' and ''Wohlfarthia magnifica'') have been found to carry ''Trichuris trichiura''. A study in two localized areas in Ethiopia found cockroaches were carriers for several human intestinal parasites, including ''T. trichiura''.


Transmission

Humans can become infected with the parasite due to ingestion of infective eggs by mouth contact with hands or food contaminated with egg-carrying soil. However, there have also been rare reported cases of transmission of ''T. trichiura'' by sexual contact. Some major outbreaks have been traced to contaminated
vegetables Vegetables are parts of plants that are consumed by humans or other animals as food. The original meaning is still commonly used and is applied to plants collectively to refer to all edible plant matter, including the flowers, fruits, stems ...
(due to presumed
soil contamination Soil contamination, soil pollution, or land pollution as a part of land degradation is caused by the presence of xenobiotic (human-made) chemicals or other alteration in the natural soil environment. It is typically caused by industrial activity ...
).


Life cycle

Unembryonated eggs (unsegmented) are passed in the feces of a previous host to the soil. In the soil, these eggs develop into a 2-cell stage (segmented egg) and then into an advanced cleavage stage. Once at this stage, the eggs embryonate and then become infective, a process that occurs in about 15 to 30 days). Next, the infective eggs are ingested by way of soil-contaminated hands or food and hatch inside the small intestine, releasing larvae into the gastrointestinal tract. These larvae burrow into a
villus Villus ( la, "shaggy hair", plural villi) may refer to: * Intestinal villus, refers to any one of the small, finger-shaped outgrowths of the epithelial lining of the wall of the intestine. Clusters of projections are referred as intestinal villi. ...
and develop into adults (over 2–3 days). They then migrate into the
cecum The cecum or caecum is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix, to which it is joined). The wo ...
and
ascending colon ''Ascending'' is a science fiction novel by the Canadian writer James Alan Gardner, published in 2001 by HarperCollins Publishers under its various imprints.HarperCollins, Avon, HarperCollins Canada, SFBC/Avon; paperback edition 2001, Eos Books. ...
where they thread their anterior portion (whip-like end) into the tissue mucosa and reside permanently for their year-long lifespan. About 60 to 70 days after infection, female adults begin to release unembryonated eggs (oviposit) into the cecum at a rate of 3,000 to 20,000 eggs per day, linking the life cycle to the start.


Incubation period

* The exact incubation period of ''T. trichiura'' is unknown, however, immature eggs in soil under favorable conditions take about three weeks to mature: 15–30 days, 10 days minimum to mature before ideal ingestion by the human host. Favorable conditions for maturation of eggs is warm to temperate climates with adequate humidity or precipitation, as ova are resistant to cold, but not resistant to drying. * Once ingested, the larva will remain dug into a villus in the small intestine for about 2–3 days until it is fully developed for migration to the ileocecal section of the gastrointestinal tract. * The average total life span of ''T. trichiura'' is one year, although there have been longer cases reported, lasting as long as five years (Note: inadequate treatment and re-infection are likely to play a role in this).


Morphology

Adult worms are usually long, with females being larger than males as is typical of nematodes. The thin, clear majority of the body (the anterior, whip-like end) is the esophagus, and it is the end that the worm threads into the mucosa of the colon. The widened, pinkish gray region of the body is the posterior, and it is the end that contains the parasite's intestines and reproductive organs. ''T. trichiura'' eggs are
prolate spheroid A spheroid, also known as an ellipsoid of revolution or rotational ellipsoid, is a quadric surface obtained by rotating an ellipse about one of its principal axes; in other words, an ellipsoid with two equal semi-diameters. A spheroid has ci ...
s, the shape of the balls used in Rugby and
Gridiron football Gridiron football,"Gridiron football"
''Encyclopædia Britannica''. Ret ...
. They are about long and have polar plugs (also known as refractile prominences) at each end.


Diagnosis

A stool ova and parasites exam reveals the presence of typical whipworm eggs. Typically, the Kato-Katz thick-smear technique is used for identification of the ''Trichuris trichiura'' eggs in the stool sample. Trichuria eggs often appear larger and more swollen on Kato-Katz preparation compared to when using other techniques. Although colonoscopy is not typically used for diagnosis, as the adult worms can be overlooked, especially with imperfect colon, there have been reported cases in which colonoscopy has revealed adult worms. Colonoscopy can directly diagnose trichuriasis by identification of the threadlike form of worms with an attenuated, whip-like end. Colonoscopy has been shown to be a useful diagnostic tool, especially in patients infected with only a few male worms and with no eggs presenting in the stool sample. Trichuriasis can be diagnosed when ''T. trichiura'' eggs are detected in stool examination. Eggs will appear barrel-shaped and un embryonated, having bipolar plugs and a smooth shell. Rectal prolapse can be diagnosed easily using
defecating proctogram Defecography (also known as proctography, defecating/defecation proctography, evacuating/evacuation proctography or dynamic rectal examination) is a type of medical radiological imaging in which the mechanics of a patient's defecation are visual ...
and is one of many methods for imaging the parasitic infection. Sigmoidoscopys show characteristic white bodies of adult worms hanging from inflamed mucosa ("coconut cake rectum").


Prevention


Deworming

Limited access to essential medicine poses a challenge to the eradication of trichuriasis worldwide. Also, it is a public health concern that rates of post-treatment re-infection need to be determined and addressed to diminish the incidence of untreated re-infection. Lastly, with mass drug administration strategies and improved diagnosis and prompt treatment, detection of an emergence of antihelminthic drug resistance should be examined. Mass Drug Administration (preventative chemotherapy) has had a positive effect on the disease burden of trichuriasis in East and West Africa, especially among children, who are at highest risk for infection.


Sanitation

Infection can be avoided by proper disposal of human feces, avoiding fecal contamination of food, not eating soil, and avoiding crops fertilized with untreated human feces. Simple and effective proper hygiene such as washing hands and food is recommended for control. Improved facilities for feces disposal have decreased the incidence of whipworm. Handwashing before food handling, and avoiding ingestion of soil by thorough washing of food that may have been contaminated with egg-containing soil are other preventive measures. In addition to washing, it is also advisable to peel and/or cook fruits and vegetables. Improvement of sanitation systems, as well as improved facilities for feces disposal, have helped to limit defecation onto soil and contain potentially infectious feces from bodily contact. A study in a Brazilian urban centre demonstrated a significant reduction in prevalence and incidence of
soil-transmitted helminthiasis Soil-transmitted helminthiasis is a type of helminth infection (helminthiasis) caused by different species of roundworms. It is caused specifically by those worms which are transmitted through soil contaminated with faecal matter and are therefo ...
, including trichuriasis, following implementation of a citywide sanitation program. A 33% reduction in the prevalence of trichuriasis and a 26% reduction in the incidence of trichuriasis was found in a study performed on 890 children ages 7–14 years old within 24 different sentinel areas chosen to represent the varied environmental conditions throughout the city of Salvador, Bahia, Brazil. Control of soil fertilizers has helped eliminate the potential for contact of human fecal matter and fertilizer in the soil.


Treatment

Trichuriasis is treated with
benzimidazole Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a colorless solid. Preparation Benzimidazole is produced by condensation of o ...
anthelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may ...
agents such as
albendazole Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, ho ...
or
mebendazole Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disea ...
, sometimes in conjunction with other medications. Mebendazole is 90% effective in the first dose. Higher clearance rates can be obtained by combining mebendazole or albendazole with
ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat i ...
. The safety of ivermectin in children under and pregnant women has not yet been established. In people with diarrhea,
loperamide Loperamide, sold under the brand name Imodium, among others,Drugs.co Page accessed September 4, 2015 is a medication used to decrease the frequency of diarrhea. It is often used for this purpose in inflammatory bowel disease and short bowel syn ...
may be added to increase the contact time between anthelmintic agents and the parasites. Oral iron supplementation may be useful in treating the
iron-deficiency anemia Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
which often accompanies trichuriasis.


Epidemiology


Regions

Infection of ''T. trichiura'' is most frequent in areas with tropical weather and poor sanitation practices. Trichuriasis occurs frequently in areas in which untreated human feces is used as fertilizer or where
open defecation Open defecation is the human practice of defecating outdoors ("in the open") rather than into a toilet. People may choose fields, bushes, forests, ditches, streets, canals, or other open spaces for defecation. They do so either because they d ...
takes place. Trichuriasis infection prevalence is 50 to 80 percent in some regions of Asia (noted especially in China and Korea) and also occurs in rural areas of the southeastern United States.


Infection estimates

''T. trichiura'' is the third most common
nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant- parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
(roundworm) infecting humans. Infection is most prevalent among children, and in North America, infection occurs frequently in immigrants from tropical or sub-tropical regions. It is estimated that 600–800 million people are infected worldwide, with 3.2 billion individuals at risk because they live in regions where this intestinal worm is common.


History

The first written record of ''T. trichiura'' was made by the Italian anatomist
Giovanni Battista Morgagni Giovanni Battista Morgagni (25 February 1682 – 6 December 1771) was an Italian anatomist, generally regarded as the father of modern anatomical pathology, who taught thousands of medical students from many countries during his 56 years as Prof ...
, who identified the presence of the parasite in a case of worms residing in the colon in 1740. An exact morphological description and accurate drawings were first recorded in 1761 by
Johann Georg Roederer Johann Georg Roederer (13 May 1726 – 4 April 1763) was a German physician and obstetrician who was a native of Strasbourg. He was father-in-law to historian August Ludwig von Schlözer (1735–1809). Roederer studied medicine at Leiden, Paris ...
, a German physician. Soon after, the name ''Trichuris trichiura'' was given to this species.


Synonyms

Human whipworm, trichocephaliasis, and tricuriasis are all synonyms for trichuriasis, human infection of the ''T. trichiura'' intestinal nematode. In Spanish, trichuriasis is called tricuriasis, while in it is known as trichuriose in French and Peitschenwurmbefall in German.


Research

Development of subunit vaccines requires the identification of protective
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
and their formulation in a suitable
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesi ...
. ''
Trichuris muris ''Trichuris muris'' is a nematode parasite of mice. It is very similar to the human roundworm parasite '' Trichuris trichiura'' due to its immunological reactivity when crossed, and so is often used in related studies. Lifecycle Ingesting m ...
'' is an antigenically similar laboratory model for ''T. trichiura''. Subcutaneous vaccination with adult excretory–secretory products (ES) protects susceptible mouse strains from ''T. muris''. Larval stages may contain novel and more relevant antigens which when incorporated in a vaccine induce worm expulsion earlier in infection than the adult worm products.
Nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant- parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
vaccines marketed to date have been of the
irradiated Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve ...
larval type and used exclusively for the treatment of animals. These vaccines are not stable and require annual production, involving the yearly production and sacrifice of donor animals for passage. There has been much interest in the production of subunit vaccines against human and agricultural parasites since the early 1980s. Development of subunit vaccines requires the identification of protective antigens and their formulation with a suitable adjuvant to stimulate the immune response appropriately.


References


External links

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