Microsporidia/Microsporidiosis

General Characteristics and Epidemiology

Basic features of microsporidia

• Recently reclassified as a group of fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology (previously classified as protozoa Protozoa Nitroimidazoles) and includes approximately:
  • 200 genera
  • 1500 species
• Vary in:
  • Spore size
  • Nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles arrangement
  • Life cycle
• Obligate intracellular 
• Unicellular Unicellular Cell Types: Eukaryotic versus Prokaryotic
• Spore-forming 
  • Usually oval
  • Resistant to degradation (survive for long months in the environment)
  • Contain a unique organelle called a polar tubule (or filament) → helps inject spore contents into a host cell
• Lack many eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic organelles Organelles A cell is a complex unit that performs several complex functions. An organelle is a specialized subunit within a cell that fulfills a specific role or function. Organelles are enclosed within their own lipid bilayers or are unbound by membranes. The Cell: Organelles, including:
  • Conventional mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles (contain mitosomes instead)
  • Peroxisomes Peroxisomes Microbodies which occur in animal and plant cells and in certain fungi and protozoa. They contain peroxidase, catalase, and allied enzymes. The Cell: Organelles
  • Golgi apparatus

Clinically relevant species

Microsporidiosis is caused by approximately 15 species, including:

• Enterocytozoon bieneusi is the most common species causing human infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.
• Encephalitozoon intestinalis
• Encephalitozoon hellem
• Encephalitozoon cuniculi
• Nosema connori
• N. ocularum
• Trachipleistophora hominis
• T. anthropopthera
• Pleistophora spp.
• Vittaforma corneae
• Microsporidium spp.

Epidemiology

• Worldwide distribution
• Most infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease occur in individuals with HIV HIV Anti-HIV Drugs/ AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS.

Pathogenesis

Reservoirs

Microsporidia have an extensive range of reservoirs, including (but not limited to):

• Humans
• Swine
• Primates
• Cattle
• Cats
• Dogs
• Rodents
• Fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing
• Birds
• Mosquitos
• Honeybees

Host risk factors

Though mild or subclinical disease may occur in immunocompetent individuals, most symptomatic infection occurs in those who are immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis:

• HIV HIV Anti-HIV Drugs/ AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS (particularly if CD4 < 100 cells/µL)
• Individuals with solid organ transplants
• Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis graft Graft A piece of living tissue that is surgically transplanted Organ Transplantation recipients

Transmission

Transmission of microsporidia is not fully understood, but possibilities include:

• Waterborne
• Foodborne
• Contact with infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic 
• Vectorborne
• Airborne

Life cycle and pathophysiology

The pathophysiology is not completely understood.

• Spore (infective form) can persist in the environment for months
• Spore enters host (e.g., inhalation, ingestion) → lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy or GI tract
• Germination occurs, and polar tubule injects sporoplasm into a host cell
• Proliferation occurs via either:
  • Binary fission Binary fission Cell Types: Eukaryotic versus Prokaryotic
  • Schizogony (multiple fission)
• Multinucleate plasmodial forms produced → sporogony (maturation process) → mature spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax formed
• Cell ruptures, and spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax are released to either:
  • Infect other cells
  • Pass into the environment (shed in feces)
• Some species can, via macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, disseminate to other organs:
  • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
  • Eyes
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
  • Biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy
  • Muscle

Clinical Presentation

The clinical presentation of microsporidiosis depends on:

• The species causing infection
• The immune status of the host:
  • Immunocompetent individuals more often experience:
    • Asymptomatic infection or
    • Mild and self-limited disease
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals are more likely to have:
    • Symptomatic infection
    • Disseminated disease

GI infection

• Acute disease (more common in immunocompetent individuals):
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Watery
    • Nonbloody
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics 
  • Abdominal pain Abdominal Pain Acute Abdomen
• Chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (more common in individuals with AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS):
  • Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery (can cause severe wasting)

Extraintestinal infection

• Ocular infection ( keratoconjunctivitis Keratoconjunctivitis Simultaneous inflammation of the cornea and conjunctiva. Stevens-Johnson Syndrome)
• Myositis
• Biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy:
  • Acalculous cholecystitis Acalculous cholecystitis Inflammation of the gallbladder wall in the absence of gallstones. Cholecystitis
  • Cholangitis
• Respiratory:
  • Sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis
  • Pneumonitis Pneumonitis Human Herpesvirus 6 and 7
  • Bronchiolitis Bronchiolitis Inflammation of the bronchioles. Pediatric Chest Abnormalities
• Urinary:
  • Impaired renal function
  • Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection
• CNS infection

Diagnosis and Management

Diagnosis

• The diagnosis is made with detection of spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax.
  • Samples can be obtained of:
    • Stool
    • Tissue
    • Body fluids
  • Requires a modified trichrome stain: spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax are stained pink
• Other options:
  • Indirect immunofluorescence 
  • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) to detect organism DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure

Management

• The following antimicrobials are effective against most species of microsporidia:
  • Albendazole Albendazole A benzimidazole broad-spectrum anthelmintic structurally related to mebendazole that is effective against many diseases. Anthelmintic Drugs
  • Fumagillin
• Antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs for individuals with AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
• IV fluid and electrolyte replacement for severe diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
• Nutritional support for those with malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery

Differential Diagnosis

• Cystoisosporiasis Cystoisosporiasis Cystoisospora is a genus within the Coccidia subclass of protozoans. They are single-celled, obligate intracellular parasites that cause intestinal infections in humans. Humans are the only host for these species, and they are both transmitted through the fecal-oral route. The symptoms of cystoisosporiasis are watery diarrhea, abdominal pain, and fever. Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis: infection caused by Cystoisospora belli Cystoisospora Belli Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis, an obligate intracellular protozoan that causes GI disease. Immunocompetent individuals may have mild, self-limited watery diarrhea Watery diarrhea Rotavirus. Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals tend to have chronic or severe diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, resulting in malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration. Diagnosis is made by identifying oocysts in stool samples. Treatment includes supportive care and antimicrobial therapy, such as trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim– sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim. 
• Cyclosporiasis Cyclosporiasis Cyclospora is a genus within the Coccidia subclass of protozoans. They are single-celled, obligate intracellular parasites that cause intestinal infections in humans. Humans are the only host for these species, and they are both transmitted through the fecal-oral route. The symptoms of cyclosporiasis are watery diarrhea, abdominal pain, and fever. Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis: infection caused by Cyclospora cayetanensis Cyclospora Cayetanensis Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis, an obligate intracellular protozoan that causes GI disease. The disease causes watery diarrhea Watery diarrhea Rotavirus, which can last weeks to months if untreated. Diagnosis is made by identifying oocysts in stool samples. Treatment includes antimicrobial therapy, such as with trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim– sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim. 
• Gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and intestines, commonly caused by infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease from bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology, viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology, or parasites. Most cases are viral. Common clinical features include abdominal pain Abdominal Pain Acute Abdomen, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration. Diagnostic testing with stool analysis or culture is not always required but can help determine the etiology in certain circumstances. Most cases are self-limited; therefore, the only required treatment is supportive therapy (fluids). 
• Cryptosporidiosis: infection with Cryptosporidium Cryptosporidium A genus of coccidian parasites of the family cryptosporidiidae, found in the intestinal epithelium of many vertebrates including humans. Hyper-IgM Syndrome. Individuals will have watery diarrhea Watery diarrhea Rotavirus, abdominal cramping Abdominal cramping Norovirus, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever that lasts 2–3 weeks, but the infection can be more persistent and severe in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals. Diagnosis is with identification Identification Defense Mechanisms of the organism in a stool specimen. Cryptosporidiosis is generally self-limited, but it may require nitazoxanide in persistent or severe cases.  
• Giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis: caused by Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles lamblia, a flagellated protozoan that can infect the intestinal tract. The hallmark symptom of giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis is foul-smelling steatorrhea Steatorrhea A condition that is characterized by chronic fatty diarrhea, a result of abnormal digestion and/or intestinal absorption of fats. Diarrhea. Individuals who develop chronic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease may experience weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive, and vitamin deficiencies as a result of malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion. The diagnosis is made through detection of Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles organisms, antigens, or DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure in the stool. Management includes supportive treatment and antimicrobial therapy with metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess, tinidazole Tinidazole A nitroimidazole alkylating agent that is used as an antitrichomonal agent against trichomonas vaginalis; entamoeba histolytica; and giardia lamblia infections. It also acts as an antibacterial agent for the treatment of bacterial vaginosis and anaerobic bacterial infections. Nitroimidazoles, or nitazoxanide. 
• Traveler’s diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea: gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis that is usually caused by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology or viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology in the local water, such as enterotoxigenic E. coli (ETEC) or norovirus Norovirus Norovirus is a nonenveloped, single-stranded, positive-sense RNA virus belonging to the Caliciviridae family. Norovirus infections are transmitted via the fecal-oral route or by aerosols from vomiting. The virus is one of the most common causes of nonbacterial gastroenteritis epidemic worldwide. Symptoms include watery and nonbloody diarrhea, nausea, vomiting, and low-grade fever. Norovirus. Symptoms occur after consumption of contaminated water or food and include watery diarrhea Watery diarrhea Rotavirus, malaise Malaise Tick-borne Encephalitis Virus, and abdominal cramping Abdominal cramping Norovirus. The diagnosis is clinical, and the illness is self-limited.