Cryptosporidiosis.txt

Cryptosporidiosis

Signs and symptoms
Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), as recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and as a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent. It may be fatal in individuals with a severely compromised immune system. Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals; symptoms are usually more severe and persist longer in immunocompromised individuals.  Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection. The likelihood of re-infection is high in immunocompromised adults, and low in those with normal immune systems.
In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well.  In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder; pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis.
Intestinal cryptosporidiosis
Common signs and symptoms of intestinal cryptosporidiosis include:
Less common or rare signs and symptoms include:
Respiratory cryptosporidiosis
Symptoms of upper respiratory cryptosporidiosis include:
Symptoms of lower respiratory cryptosporidiosis include:

Diagnosis
There are many diagnostic tests for Cryptosporidium.  They include microscopy, staining, and detection of antibodies. Microscopy can help identify oocysts in fecal matter.  To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples.  There are several techniques to concentrate either the stool sample or the oocysts.  The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool.  Both the modified zinc sulfate centrifugal flotation technique and the Sheather's sugar flotation procedure can concentrate the oocysts by causing them to float.  Another form of microscopy is fluorescent microscopy done by staining with auramine.
Other staining techniques include acid-fast staining, which will stain the oocysts red.  One type of acid-fast stain is the Kinyoun stain. Giemsa staining can also be performed.  Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.
Detecting antigens is yet another way to diagnose the disease.  This can be done with direct fluorescent antibody (DFA) techniques.  It can also be achieved through indirect immunofluorescence assay. Enzyme-linked immunosorbent assay (ELISA) also detects antigens.
Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis.  It can even identify the specific species of Cryptosporidium.  If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique is ultrasonography.  If that returns normal results, the next step would be to perform endoscopic retrograde cholangiopancreatography.

Treatment
Symptomatic treatment primarily involves fluid rehydration, electrolyte replacement (sodium, potassium, bicarbonate, and glucose), and antimotility agents (e.g., loperamide).  Supplemental zinc may improve symptoms, particularly in recurrent or persistent infections or in others at risk for zinc deficiency.
Immunocompetent
Immunocompetent individuals with cryptosporidiosis typically experience a short (i.e., duration of less than 2 weeks) self-limiting course of diarrhea that may require symptomatic treatment and ends with spontaneous recovery; in some circumstances, antiparasitic medication may be required (e.g., recurrent, severe, or persistent symptoms); however reinfection frequently occurs.
As of 2015, nitazoxanide is the only antiparasitic drug treatment with proven efficacy for cryptosporidiosis in immunocompetent individuals; however, it lacks efficacy in severely immunocompromised patients. Certain agents such as paromomycin and azithromycin are sometimes used as well, but they only have partial efficacy.
Immunocompromised
In immunocompromised individuals, such as AIDS patients, cryptosporidiosis resolves slowly or not at all, and frequently causes a particularly severe and persistent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. As a result, infected individuals may experience severe dehydration, electrolyte imbalances, malnutrition, wasting, and potentially death. In general, the mortality rate for infected AIDS patients is based on CD4+ marker counts. Patients with CD4+ counts over 180 cells/mm³ recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within 3 to 6 months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4+ counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.
The best treatment approach is to improve the immune status in immunodeficient individuals using highly active antiretroviral therapy that includes an HIV protease inhibitor along with continued use of antiparasitic medication. Antiparasitic drug treatment for immunocompromised individuals usually involves the combination of nitazoxanide, paromomycin, and azithromycin together; these drugs are only partially active in HIV/AIDS patients compared to their effect in immunocompetent persons. A Cochrane Collaboration review recommended that nitazoxanide be considered for use in treatment despite its reduced effectiveness in immunocompromised individuals.
Currently, research is being done in molecular-based immunotherapy.  For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum both in vitro and in animal studies.  Derivates of nitazoxanide, known as thiazolides, have also shown promising results in vitro. rifaximin is also sometimes used for immunocompromised patients/patients with severe disease.