GIT worm infection; cause, transmission, treatment, and prevention

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GIT worm infection; cause, transmission, treatment, and prevention After treatment, infection can happen again. This is common in areas where roundworm infection is wi This section of the book has two types of chapters.
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Medical parasitology traditionally has included the study of three major groups of animals: parasitic protozoa, parasitic helminths (worms), and those arthropods that directly cause disease or act as vectors of various pathogens. A parasite is a pathogen that simultaneously injures and derives sustenance from its host. Some organisms called parasites are actually commensals, in that they neither b

enefit nor harm their host (for example, Entamoeba coli). Although parasitology had its origins in the zoologic sciences, it is today an interdisciplinary field, greatly influenced by microbiology, immunology, biochemistry, and other life sciences. Infections of humans caused by parasites number in the billions and range from relatively innocuous to fatal. The diseases caused by these parasites constitute major human health problems throughout the world. (For example, approximately 30 percent of the world's population is infected with the nematode Ascaris lumbricoides.) The incidence of many parasitic diseases (e.g., schistosomiasis, malaria) have increased rather than decreased in recent years. Other parasitic illnesses have increased in importance as a result of the AIDS epidemic (e.g., cryptosporidiosis, Pneumocystis carinii pneumonia, and strongyloidiasis). The migration of parasite-infected people, including refugees, from areas with high prevalence rates of parasitic infection also has added to the health problems of certain countries. A misconception about parasitic infections is that they occur only in tropical areas. Although most parasitic infections are more prevalent in the tropics, many people in temperate and subtropical areas also become infected, and visitors to tropical countries may return with a parasite infection. The unicellular parasites (protozoa) and multicellular parasites (helminths, arthropods) are antigenically and biochemically complex, as are their life histories and the pathogenesis of the diseases they cause. During their life, parasitic organisms typically go through several developmental stages that involve changes not only in structure but also in biochemical and antigenic composition. Some helminth larval stages have little resemblance to the adult stages (for example, those of tapeworms and flukes). Some parasitic protozoa also change greatly during their life history; for example, Toxoplasma gondii is an intestinal coccidian in cats but in humans takes on a different form and localizes in deep tissues. Some of these infections can convert from a well-tolerated or asymptomatic condition to life-threatening disease. Many parasitic infections are transmitted from animals to humans (zoonotic infections); the human disease may or may not resemble the disease caused in the lower animal host. Several general chapters deal with the structure and classification of parasites and the mechanisms of parasitic diseases. The remaining chapters describe the specific human parasites and the diseases they cause. Emphasis is placed throughout on the basic biology of the pathogens and their host-parasite relationships. Thus, descriptions of the basic properties of the pathogens, the pathogenesis of the diseases they cause, host defenses, and epidemiology are highlighted. Practical information on clinical manifestations, diagnosis, and control has been included in the chapters on specific pathogens. Most chapters treat a group of related pathogens (for example, trematodes, cestodes). Other chapters are more limited in scope because of the expertise of the authors and the difficulty involved in including these species in the groups discussed in the other chapters. This section gives the reader a broad, in-depth coverage of medically important parasites. Such coverage is essential to give students the awareness and understanding necessary for proper diagnosis, treatment, and prevention of the parasitic infections. The most important element in diagnosing a parasitic infection is often the physician's suspicion that a parasite may be involved—a possibility that is too often overlooked. This kind of awareness requires a knowledge of the biology of the parasites. Diagnosis of parasitic infections requires laboratory support, since the signs and symptoms are often nonspecific. A variety of methods and specimens are used for diagnosis. Since the most common parasites are enteric, microscopic examination of f***l specimens is done more often than any other laboratory procedure in the diagnosis of parasitic disease. Culturing has little application in the diagnosis of most parasitic infections, although it has been employed, for example, for Trichomonas vaginalis and Entamoeba histolytica infections. Immunodiagnostic tests are useful in several infections, including extraintestinal amebiasis, visceral larva migrans, and trichinosis. Because the laboratory is so important in diagnosis, its personnel must be well trained. Continuing training and refresher courses should be encouraged and supported. In the United States, excellent short courses in diagnostic parasitology are available in various state and federal health laboratories and at the Centers for Disease Control (CDC) in Atlanta. These laboratories also offer a variety of diagnostic services in parasitology, including specialized serologic tests. Medical scientists in the United States should be aware of the Parasitic Disease Drug Service at CDC, from which they may obtain drug information and certain drugs not readily available. Announcements of regional workshops and continuing education programs in parasitology can be found in various journals, for example the American Society for Microbiology News.

Parasitic infections, caused by intestinal helminths and protozoan parasites, are among the most prevalent infections in...
23/12/2022

Parasitic infections, caused by intestinal helminths and protozoan parasites, are among the most prevalent infections in humans in developing countries. In developed countries, protozoan parasites more commonly cause gastrointestinal infections compared to helminths. Intestinal parasites cause a significant morbidity and mortality in endemic countries.
Helminths are worms with many cells. Nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms) are among the most common helminths that inhabit the human gut. Usually, helminths cannot multiply in the human body. Protozoan parasites that have only one cell can multiply inside the human body. There are four species of intestinal helminthic parasites, also known as geohelminths and soil-transmitted helminths: Ascaris lumbricoides (roundworm), Trichiuris trichiuria (whipworm), Ancylostoma duodenale, and Necator americanicus (hookworms). These infections are most prevalent in tropical and subtropical regions of the developing world where adequate water and sanitation facilities are lacking (1,2). Recent estimates suggest that A. lumbricoides can infect over a billion, T. trichiura 795 million, and hookworms 740 million people (3). Other species of intestinal helminths are not widely prevalent. Intestinal helminths rarely cause death. Instead, the burden of disease is related to less mortality than to the chronic and insidious effects on health and nutritional status of the host (4,5). In addition to their health effects, intestinal helminth infections also impair physical and mental growth of children, thwart educational achievement, and hinder economic development
The most common intestinal protozoan parasites are: Giardia intestinalis, Entamoeba histolytica, Cyclospora cayetanenensis, and Cryptosporidium spp. The diseases caused by these intestinal protozoan parasites are known as giardiasis, amoebiasis, cyclosporiasis, and cryptosporidiosis respectively, and they are associated with diarrhoea (8). G. intestinalis is the most prevalent parasitic cause of diarrhoea in the developed world, and this infection is also very common in developing countries. Amoebiasis is the third leading cause of death from parasitic diseases worldwide, with its greatest impact on the people of developing countries. The World Health Organization (WHO) estimates that approximately 50 million people worldwide suffer from invasive amoebic infection each year, resulting in 40-100 thousand deaths annually (9,10). Cryptosporidiosis is becoming most prevalent in both developed and developing countries among patients with AIDS and among children aged less than five years. Several outbreaks of diarrhoeal disease caused by C. cayetanensis have been reported during the last decade. Spread of these protozoan parasites in developing countries mostly occurs through faecal contamination as a result of poor sewage and poor quality of water. Food and water-borne outbreaks of these protozoan parasites have occurred, and the infectious cyst form of the parasites is relatively resistant to chlorine. Other species of protozoan parasites can also be found in the human gut, but they are not pathogenic, except Microsporidia sp.
In an article published in this issue of the Journal, Jacobsen et al. looked at the prevalence of intestinal parasites in young Quichua children in the highland or rural Ecuador (13). They have found a high prevalence of intestinal parasites, especially the intestinal protozoan parasites. They have used the traditional microscopic technique to diagnose intestinal parasitic infections. In total, 203 stool samples were examined from children aged 12-60 months and found that 85.7% of them had at least on parasite. The overall prevalence of intestinal protozoan parasites were: E. histolytica/E. dispar 57.1%, Escherichia coli 34.0%, G. intestinalis 21.1%, C. parvum 8.9%, and C. mesnili 1.7%, while the prevalence of intestinal helminthic parasites in this study were: A. lumbricoides 35.5%, T. trichiura 0.5 %, H. diminuta 1.0%, and S. stercoralis 0.7%. A recent study in Nicaragua in asymptomatic individuals found that 12.1% (58/480) were positive for E. histolytica/E. dispar by microscopy, but E. histolytica and E. disapr were positive by polymerase chain reaction (PCR) only in three and four stool samples respectively among the microscopic positive samples (Unpublished data). This study proves again that the diagnosis of E. histolytica/E. dispar is neither sensitive nor specific when it is done by microscopy. To understand the real prevalence of E. histolytica-associated infection, a molecular method must be used for its diagnosis.
Over the last several years, we have seen new approaches to the diagnosis, treatment, and prevention of intestinal protozoan parasites. However, the diagnosis and treatment of intestinal helminth infections have not been changed much, and the traditional microscopic method can be used for their diagnosis. Antigen-detection tests are now commercially available for the diagnosis of all three major intestinal protozoan parasites. Diagnosis of E. histolytica cannot be done any longer by microscopy, since this parasite is morphologically similar to the non-pathogenic parasite E. dispar. E. histolytica-specific antigen-detection test is now commercially available from TechLab, Blacksburg, Virginia, for the detection of E. histolytica antigen in stool specimens. In several studies, this E. histolytica-specific antigen-detection test has been used for the specific detection of E. histolytica. These studies have found that this antigen-detection test is sensitive and specific for the detection of E. histolytica. In a study in Bangladesh, E. histolytica-specific antigen-detection test identified E. histolytica in 50 of 1,164 asymptomatic preschool children aged 2-5 years. In a study in Nicaragua among patients with diarrhoea, where E. histolytica-specific test has been used, found that the prevalence of E. histolytica was 0.5% (19). In a study conducted in a cohort of Bangladeshi children found that the prevalence of E. histolytica in diarrhoeal stool samples was 8.0% (20). No studies that have been carried till date using E. histolytica-specific diagnostic test reported the prevalence of E. histolytica more than 10%. In addition to the antigen-detection test, several PCR-based tests specific for E. histolytica have been developed and used for specific detection of E. histolytica. Rapid diagnostic test for the detection of E. histolytica antigen in stool specimens has also been reported
Diagnosis of giardiasis is best accomplished by detection of Giardia antigen in stool, since the classic microscopic examination is less sensitive and specific. A recent comparison of nine different antigen-detection tests demonstrated that all had high sensitivity and specificity, except one. Giardia-specific antigen-detection tests are now also commercially available from several diagnostic companies, and their performance is quite good, except a few. In addition to antigen-detection tests, PCR-based test for the detection of G. intestinalis has also been reported (25). The population genetics of Giardia are complex. However, a recent genetic linkage study has confirmed the distinct grouping of Giardia in two major types ). These two main genotypes/assemblages of G. intestinals are commonly known as: assemblage A and assemblage B of G. intestinalis. Differentiation of these two assemblages of G. intestinalis can only be done by PCR-based tests. Findings of the largest case-control study conducted to date on the relationship between genotypes of G. intestinalis and symptoms of patients have been published. This study has shown that the Giardia assemblage A infection is associated with diarrhoea. In contrast, Giardia assemblage B infection is significantly associated with asymptomatic Giardia-associated infection, which was found to occur at a significantly higher rate (18.0%) as detected by the antigen-detection test. The PCR-based approach allowed resolution of infection to the genotype level and brought some clarity to the findings of asymptomatic giardiasis. Similar large-scale case-control studies need to be carried out in other continents to understand more on the association of Giardia assemblages with diarrhoea/dysentery.
Diagnosis of cryptosporidiosis is also best accomplished by detection of Cryptosporidium spp. antigen in stool samples, since classic microscopic examination is less sensitive, and modified acid-fast staining is required. Cryptosporidium spp.-specific antigen-detection test has been used in several studies and has been found to be sensitive and specific compared to classic microscopic examination and PCR-based test . There are two main species of Cryptosporidium that infect humans: C. hominis (genotype I) and C. parvum (genotype II). The PCR-based test is required for differentiation of these two species of Cryptosporidium spp. Both C. hominis and C. parvum have been found in humans. There are a few other species of Cryptosporidium that also can be found in humans . Rapid diagnostic tests for the detection of G. lamblia and Cryptosporidium spp. have also been reported . Multiplex PCR-based test for the detection of E. histolytica, G. intestinalis, and Cryptosporidium spp.
Soil-transmitted helminth infections are invariably more prevalent in the poorest sections of the populations in endemic areas of developing countries. The goal is to reduce morbidity from soil-transmitted helminth infections to such levels that these infections are no longer of public-health importance. An additional goal is to improve the developmental, functional and intellectual capacity of affected children. Highly-effective, safe single-dose drugs, such as albendazole, now available, can be dispensed through healthcare services, school health programmes, and community interventions directed at vulnerable groups. As these infections are endemic in poor communities, more permanent control will only be feasible where chemotherapy is supplemented by improved water supplies and sanitation, strengthened by sanitation education. In the long term, this type of permanent transmission control will only be possible with improved living conditions through economic development. Intestinal protozoa multiply rapidly in their hosts, and as there is a lack of effective vaccines, chemotherapy has been the only practised way to treat individuals and reduce transmission. The current treatment modalities for intestinal protozoan parasites include metronidazole, iodoquinol, diloxanide furoate, paromomycin, chloroquine, and trimethoprim-sulphamethoxazole . Nitazoxanide, a broad-spectrum anti-parasitic agent, was reported to be better than placebo for the treatment of cryptosporidiosis in a double-blind study performed in Mexico. Genomes of these three important protozoan parasites have already been published (41–43), and studies are underway to understand protective immunity to these protozoan parasites to develop vaccines for them.

Common types of intestinal wormsCommon types of intestinal worms that can infect humans include:flatworms, which include...
08/09/2022

Common types of intestinal worms
Common types of intestinal worms that can infect humans include:
flatworms, which include tapeworms and flukes
roundworms, which cause ascariasis, pinworm, and hookworm infections
Tapeworms
Humans get tapeworms by eating raw or uncooked pork or beef. Species that infect humans include:
Taenia saginata (beef tapeworm)
Taenia solium (pork tapeworm)
Taenia asiatica (Asian tapeworm)
It’s thought that fewer than 1,000Trusted Source people in the United States are infected with tapeworms each year, although the exact number isn’t known. Tapeworms as long as 25 metersTrusted Source (82 feet) have been found in humans.
Flukes
More than 70 types of flukes can live in the human intestinal tract. They range from a fraction of an inch to several inches long. Humans can become infected by eating contaminated food or water. Flukes are most common in East and Southeast Asia.
Pinworms
It’s estimated that more than 1 billionTrusted Source people in the world are infected with pinworms, and they’re the most common type of worm that infects humans in North America. Children are most commonly infected. They’re easily passed between people living in close quarters.
Hookworms
It’s estimated that between 576 to 740 millionTrusted Source people are infected with hookworms. They were once common in the United States, particularly in the Southeast, but they’ve become less common as living standards have improved. Most people infected with hookworms have no symptoms.
Ascariasis
Ascariasis is an infection of Ascaris lumbricoides and affects more than 800,000 millionTrusted Source people in the world. It’s rare in the United States but may occur in the rural Southeast. Infection occurs from contaminated food or water. Adult worms can grow more than a footTrusted Source long. Usually, they don’t cause symptoms.

How to tell if you have worms in your stoolWorms in your gut eventually pass through your digestive system and are excre...
08/09/2022

How to tell if you have worms in your stool
Worms in your gut eventually pass through your digestive system and are excreted in your f***s. Even if you don’t have any symptoms, you may find signs of worms in your stool.
Worms in human p**p can take a number of appearances. For roundworms, you may find pieces of worms or large, live worms in your f***s. For pinworms, you may see thin, white worms that appear like pieces of thread. Pinworms, which are about the length of a stapleTrusted Source, are sometimes visible around the a**l region at night, when females lay their eggs on the surrounding skin.
A doctor can a**lyze a sample of your stool in a lab for signs of worms or eggs that can confirm a diagnosis.

Symptoms of intestinal wormsCommon symptoms of intestinal worms are:abdominal paindiarrhea, nausea, or vomitinggas and b...
08/09/2022

Symptoms of intestinal worms
Common symptoms of intestinal worms are:
abdominal pain
diarrhea, nausea, or vomiting
gas and bloating
fatigue
unexplained weight loss
abdominal pain or tenderness
A person with intestinal worms may also experience dysentery. Dysentery is when an intestinal infection causes diarrhea with blood and mucus in the stool. Intestinal worms can also cause a rash or itching around the re**um or v***a. In some cases, you will pass a worm in your stool during a bowel movement.
Some people may have intestinal worms for years without experiencing any symptoms.

Intestinal worms, also known as parasitic worms, are one of the main types of intestinal parasites in humans. They’re mo...
08/09/2022

Intestinal worms, also known as parasitic worms, are one of the main types of intestinal parasites in humans. They’re most commonly found in subtropical and tropical regions, but some types are found in the United States.
Most intestinal worm infections only cause mild illness and can be treated with medication. Read on to learn more about intestinal worms including signs, symptoms, and treatment.

Stomach Worms in Children : Symptoms , Treatment & Prevention TipsChildren are the future of the world and as they are t...
08/09/2022

Stomach Worms in Children : Symptoms , Treatment & Prevention Tips
Children are the future of the world and as they are tender in their thoughts, knowledge and health. It is the desire of every parent to guarantee a healthier environment and a better life for their child. However, when it comes to a child's health, many factors come into play and can sometimes be a complex task. The presence of worms in the stomach or intestine is one problem that many children face during their growing stage.
As per the World Health Organization (WHO) states, ‘Soil-borne helminth infections are one among the most common infections in humans, caused by a group of parasites, referred to as worms, including roundworms, whipworms and hookworms. These intestinal worms can seriously affect the nutrition and growth of the child. A child may undergo deworming regularly to remove the intestinal worms. Such worms need to be killed, otherwise, they can multiply and lay eggs in the intestine causing major damage to the body. Some of those intestinal parasites may even be fatal and should therefore not be overlooked. Worms also make the child more vulnerable to diseases such as intestinal obstruction and reduce the ability to sufficiently absorb vitamins. Parasitic worms also sometimes allow the child to become malnourished and/or stunted even without obvious symptoms.

TreatmentSome people with tapeworm infections never need treatment, for the tapeworm exits the body on its own. Others d...
08/09/2022

Treatment
Some people with tapeworm infections never need treatment, for the tapeworm exits the body on its own. Others don't realize they have it because they have no symptoms. However, if you're diagnosed with intestinal tapeworm infection, medication will likely be prescribed to get rid of it.
Treatments for intestinal infections
The most common treatment for tapeworm infection involves oral medications that are toxic to the adult tapeworm, including:
Praziquantel (Biltricide)
Albendazole (Albenza)
Nitazoxanide (Alinia)
Which medication your doctor prescribes depends on the species of tapeworm involved and the site of the infection. These drugs target the adult tapeworm, not the eggs, so it's important to avoid reinfecting yourself. Always wash your hands after using the toilet and before eating.
To be certain that your tapeworm infection has cleared, your doctor will probably have your stool samples checked at certain intervals after you've finished taking your medication. Successful treatment — meaning that your stool is free of tapeworm eggs, larvae or proglottids — is most likely if you receive appropriate treatment for the type of tapeworm causing your infection.
Treatments for invasive infections
Treating an invasive infection depends on the location and effects of the infection.
Anthelmintic drugs. Albendazole (Albenza) can shrink some tapeworm cysts. Your doctor may monitor the cysts periodically using imaging studies such as ultrasound or X-ray to be sure the drug is effective.
Anti-inflammatory therapy. Dying tapeworm cysts can cause swelling or inflammation in tissues or organs, so your doctor may recommend prescription corticosteroid medication, such as prednisone or dexamethasone, to reduce inflammation.
Anti-epileptic therapy. If the disease is causing seizures, anti-epileptic medications can stop them.
Shunt placement. One type of invasive infection can cause too much fluid on the brain, called hydrocephalus. Your doctor may recommend placing a permanent tube (shunt) in your head to drain the fluid.
Surgery. Whether cysts can be removed surgically depends on their location and symptoms. Cysts that develop in the liver, lungs and eyes are typically removed, since they can eventually threaten organ function.
Your doctor might recommend a drainage tube as an alternative to surgery. The tube allows aggressive rinsing (irrigation) of the area with anti-parasitic solutions.

TreatmentAnthelmintic medications (drugs that remove parasitic worms from the body), such as albendazole and mebendazole...
08/09/2022

Treatment
Anthelmintic medications (drugs that remove parasitic worms from the body), such as albendazole and mebendazole, are the drugs of choice for treatment of Ascaris infections, regardless of the species of worm. Infections are generally treated for 1–3 days. The drugs are effective and appear to have few side effects.

10/08/2022

Hookworms are parasites. This means they live off other living things. Hookworms affect your lungs, skin, and small intestine. Humans contract hookworms through hookworm larvae found in dirt contaminated by f***s.
According to the Centers for Disease Control and Prevention, hookworm infections occur in an estimated 576 to 740 millionTrusted Source people worldwide. It mainly affects people in developing nations in the tropics and subtropics due to poor sanitation. These infections rarely occur in the United States.
What are the symptoms of a hookworm infection?
You might not have any symptoms from the infection if you’re otherwise healthy, have a low parasite burden, and eat foods with plenty of iron.
If you do experience symptoms, they generally start with itchiness and a small rash caused by an allergic reaction in the area that the larvae entered your skin. This is generally followed by diarrhea as the hookworms grow in your intestine. Other symptoms include:
abdominal pain
colic, or cramping and excessive crying in infants
intestinal cramps
nausea
a fever
blood in your stool
a loss of appetite
itchy rash

What is roundworm infection in children?Roundworm infection is a type of parasitic illness. This is an illness in which ...
24/07/2022

What is roundworm infection in children?
Roundworm infection is a type of parasitic illness. This is an illness in which an organism lives inside the body of another creature. It’s caused by a type of roundworm. The worms live and grow inside the body and may cause symptoms.
What causes roundworm infection in a child?
Roundworm infection is the most common type of worm infection in the world. It is rare in the U.S. Roundworm eggs live in soil that is contaminated by f***s. The eggs can get into the body through the mouth. The infection can then spread from person to person through infected f***s.
Roundworms can live inside the small intestine for up to 2 years. The worms are about as thick as a pencil. They can grow to be about 13 inches long. They reproduce very quickly. Female roundworms may lay more than 200,000 eggs a day. These eggs leave the body through bowel movements.
If a child swallows a roundworm egg, it passes down into the intestine and hatches into a baby worm (larva). Larvae can pass through the intestine wall into the bloodstream. They then travel through the lungs up into the throat. They are then swallowed again and return to the small intestine. There they grow into adult worms.
Which children are at risk for roundworm infection?
Roundworms tend to be more common in warm, wet, tropical countries. They are more common in countries where
People live in poverty
There is inadequate disposal of human f***s
Crops are fertilized with human f***s
Your child may be at risk for roundworm infection if he or she has been adopted from a developing country. Or if you have traveled to a place where roundworms are common. Children are more likely to be infected after playing in contaminated soil and putting their contaminated hands into their mouths. A child may also be infected after eating unwashed fruits and vegetables that were grown in contaminated soil.
What are the symptoms of roundworm infection in a child?
Older children may have no symptoms. A younger child may be more likely to have symptoms. This is because their intestines are narrower and the worms have less room. Symptoms may include:
Worms in a bowel movement that look like earthworms
Worms coming out of the nose or mouth
Stomach pain
Coughing
Loss of appetite
Fever
Wheezing
Weight loss or failure to grow
If worms block the intestine, this may cause:
Vomiting
Belly (abdomen) that is painful, bloated, and hard
The symptoms of roundworm infection can seem like other health conditions. Have your child see his or her healthcare provider for a diagnosis.
How is roundworm infection diagnosed in a child?
The healthcare provider will ask about your child’s symptoms and health history. He or she may also ask about your family’s travel history. He or she will give your child a physical exam. Your child may also have a stool sample test. For this, a small sample of your child’s f***s is checked in a lab to look for roundworm eggs or worms.
How is roundworm infection treated in a child?
In most cases, roundworms can be easily treated by taking a medicine that kills the worms in about 3 days. Talk with your child’s healthcare provider about the risks, benefits, and possible side effects of all medicines. Medicines often used in the U.S. are:
Albendazole
Mebendazole
Pyrantel
In rare cases, your child may need surgery to treat a severe intestinal blockage caused by roundworms.

Roundworms shed light on vision loss in a rare human genetic disorderWhat do we currently know about the clinical manife...
04/07/2022

Roundworms shed light on vision loss in a rare human genetic disorder
What do we currently know about the clinical manifestation and causes of Bardet-Biedl syndrome, and what are the unknowns that limit the treatment of this disorder?
The clinical manifestation of Bardet-Biedl Syndrome is very complex, and the symptoms and severity can vary for an individual patient. The primary symptoms that are found common in most patients are progressive vision loss, excess hunger, early-onset obesity, learning disability, reduced kidney function, and extra fingers or toes.
BBS is an autosome recessive rare genetic disease, and more than 20 genes are associated with BBS. BBS is one of the model ciliopathies, which is believed to be a cilia disease. Cilia are antenna-like cell surface organelles in most human cells and are essential for perceiving and transducing cell signals.
The lack of understanding of BBS pathology greatly hinders the treatment of this disease. It is currently unknown how BBS affects several vital organs (e.g., eyes, kidney, and central nervous system) and why patients display a wide spectrum of symptoms with different severity, regardless of the critical roles of BBS proteins in cilia.
Please tell us how you carried out your research and what were your main findings?
I tried to understand how the photosensation is regulated in a specific pair of neurons, called ASH, in C. elegans. I expressed a Genetic Encoded Calcium Indicator (GECI) in ASH neurons, and the neurons will turn bright when shining a light on the worm.
We performed a genetic screen by introducing many random genetic mutations to the DNA of the worms. We selected the mutant worms which lose the ability to turn bright upon shining a light. We found that many BBS-related genes are required for worm photosensation.
Several BBS proteins form a core complex called BBSome, and the best-known function of BBSome is that it helps maintain cilia's function by transporting cargoes in and out of cilia. However, we found photosensation in ASH neurons does not require cilia at all. By removing all the cilia structures from the worm using a ciliogenesis mutant worm, we found the mutant worm responds normally to light. Furthermore, by excluding the BBSome entering cilia using another mutant worm, this mutant worm again reacts normally. Thus, we concluded that BBSome could function outside the cilia to regulate photosensation in the worm.
To understand the signaling pathway that acts downstream of BBSome to regulate photosensation, we carried another round of genetic screen, called suppressor screen. We tried to isolate mutant worms which can suppress the light-insensitive phenotype of bbs mutant worms. In other words, we want to cure bbs mutant worms. Then, we found DLK-1, a MAPKKK kinase, is the downstream effector of BBSome. Loss of function of DLK-1 ultimately rescued the light insensitive phenotype of bbs mutants.
Through a series of other experiments, we figured out that BBSome acts outside cilia to inhibit DLK-1 and maintain light sensitivity in wild-type worms. While in bbs mutants, this inhibition is gone, and DLK-1 gets activated. The photoreceptor protein is degraded through endocytosis machinery after DLK-1 is activated. Thus, bbs mutants eventually lose light sensitivity.
In your study, you performed a genetic screen. Could you tell us more about this experimental technique and its importance in studying genetic disorders?
A genetic screen is to investigate the functions of genes, usually done so by following a specific phenotype. For example, in our initial genetic screen, we followed the phenotype of mutant worms that cannot turn bright upon shining a light. Since random mutations were introduced to the worm population using a chemical mutagen, ethyl methanesulfonate (EMS), we did not immediately know the causal genes responsible for the light-insensitive phenotype in the mutants we isolated. We need to do whole genome sequencing and genetic mapping to identify the causal genes.This kind of screen is called a forward genetic screen.
In contrast, in a reverse genetic screen, a user-defined gene is silenced in a given individual or population at a time to screen for a particular phenotype. In this case, the causal genes are immediately known by the researchers.
For genetic disorders in which the pathology is unclear, like BBS, the genetic screen will be handy to understand the underlying mechanism and thus accelerate the therapy development. We usually carry genetic screens when we know little about the underlying mechanisms of a particular phenotype, like the symptoms of BBS, to discover the genetic pathways that ultimately contribute to the phenotype. BBS-related genes are conserved even in C. elegans. The bbs mutants also display similar phenotypes as seen in BBS patients, such as obesity, learning disability, and vision loss. In this case, C. elegans has a significant advantage in helping to understand more about BBS by carrying genetic screens.
How may your findings influence the understanding and treatment of vision loss in Bardet-Biedl syndrome?
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We found that BBSome could function outside the cilia to regulate photosensation in the worm. The downstream genetic pathway that gives the worm the vision loss phenotype involves DLK-1/p38 MAPK and endocytosis. Future studies need to demonstrate if DLK-1/p38 or endocytosis pathway is also involved in retinal degeneration in mouse BBS models or human BBS patients and whether BBSome could function independently of cilia in mice or humans.
Besides, our findings also provide a new angle to understanding the pathology of BBS, which is the symptoms, or at least some of the symptoms might not result from cilia defects. In addition, we also demonstrated the possibility of treating BBS outside cilia by showing that silencing DLK-1 (not found in cilia) can suppress the bbs mutant worm.
What makes C. elegans such a good model organism, and how does studying such a seemingly simple organism inform research into human health?
First of all, C. elegans is an animal, and many of the biological reactions in worms are similar in humans. Besides that, C. elegans is easy to culture in the laboratory and can make more than 300 copies of itself within three days, and C. elegans strain can be revived whenever needed from a freezing stock in a freezer. Rich genetic tools are also available to dissect gene functions in C. elegans. Most importantly, many of the C. elegans genes have counterparts in humans, such as bbs genes, and many of the cellular pathways are also conserved in humans, such as DLK/p38 MAPK cascade. For the human diseases modeled in C. elegans, such as BBS, the genetic screen can provide many insights to help understand their pathologies.
Your study provides support for a cilia-independent hypothesis for Bardet-Biedl syndrome-induced vision loss. Considering this disorder has been classified as a disease of the cilia, how important is it to explore alternative hypotheses in medical science?
We are not arguing the critical functions of BBSome in cilia which many beautiful studies have demonstrated. However, currently, it is unclear how the cilia functions of BBSome contribute to the manifestations of BBS. It is essential to understand the underlying mechanism of the wide spectrum of the symptoms of BBS patients. To achieve the goal of curing BBS, it is always important to keep an open mind and have alternative hypotheses in medical science, especially at this stage, we do not know much about the pathology of this disease.
Some studies have already indicated that BBSome is present in the cell outside the cilia, even in mice. So, does the BBSome outside cilia contribute to the symptoms of BBS? Our study provides alternative thinking about the pathology of BBS. For example, are all symptoms of BBS caused by common downstream effectors in different organs, are all symptoms linked with the cilia or cilia function of BBSome, is it possible to treat the BBS outside the cilia?
What is next for you and your research?
It is the 6th year of my postdoctoral training, and I will look for a faculty job to continue my research interest this year. For the BBSome project, there are also many exciting questions to follow. I am going to explore some of the questions in my own lab, for example, how the BBSome inhibits DLK-1, why the light-sensitivity loss is age-dependent, how BBSome functions differently in different neurons, does the DLK/p38 MAPK pathway is also involved in obesity and learning disability in C. elegans, and are there additional pathways act downstream of BBSome.

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