What is Cryptosporidiosis?
Cryptosporidiosis is a human protozoal disease that usually occurs in the gastrointestinal form of its osmotic hypofermentative diarrhea and takes severe forms in individuals with immunodeficiency.
Cryptosporidia was first discovered in 1907 by E. Tyzzer in the gastric mucosa of a laboratory mouse without evidence of pathology of the gastrointestinal tract. This microorganism has been considered a “harmless” commensal for more than 50 years. In 1955, the first case of cryptosporidiosis in animals was registered – cryptosporidia was isolated in fatal gastroenteritis in poultry. Since 1970, cryptosporidia have been found in the gastrointestinal tract (GIT) and / or the respiratory tract of most mammals, birds, fish, and reptiles.
The first case of human cryptosporidiosis was described in 1976, and in the early 1980s it became clear that members of the genus Cryptosporidium often cause infections in humans, which is associated not only with improved diagnostics, but also with a significant increase in the number of persons with immunodeficiency states first of all with acquired immunodeficiency syndrome (AIDS).
Causes of Cryptosporidiosis
The genus Cryptosporidium (from the Greek. Hidden dispute) belongs to the family Cryptosporidiidae, a subtype of Apicomplexa (due to the fact that sporozoites have apical complexes), the class Sporozoasida, a subclass of Coccidiasina.
Cryptosporidia are obligate parasites infecting the microvilli of the mucous membranes of the gastrointestinal tract and the respiratory tract of animals and humans. Initially, it was believed that various cryptosporidia are strictly specific to a certain type of vertebrate or human, and therefore their classification was based on the animals they infect. However, later experiments on cross-infection showed that different cryptosporidia are much less specific than previously thought.
In this regard, in 1984, the previously existing species (21 species) were combined into 4 species. Currently, the genus Cryptosporidium officially includes 6 species: C. nasorum, infecting fish, C. serpentis, infecting reptiles, C. baileyi and C. meleagrides, infecting birds, C. muris and C. parvum, infecting mammals. It should be emphasized that almost all cases of cryptosporidiosis in humans were caused by C. parvum.
The development cycle of cryptosporidium is “exclusive”, that is, all development cycles occur in the body of the same host.
Epidemiology. Infections of the gastrointestinal tract caused by cryptosporidia are registered in all age groups and on all continents, with the exception of Antarctica. Such a wide distribution of cryptosporidiosis is associated with a large number of natural reservoirs of infection, low infectious dose and high resistance of the pathogen to disinfectants and antiparasitic drugs. Children, especially those under 2 years of age, are more susceptible than adults. Cumulative incidence of cryptosporidiosis is about 1-3% in industrialized countries and 5-10% in developing ones.
It should be noted that the underdiagnosis of this disease is associated with the imperfection of diagnostic techniques and the need for special staining of samples, which is not carried out in all laboratories. The results of serological studies indicate that, probably, cryptosporidiosis occurs much more frequently than it is diagnosed. Thus, antibodies to cryptosporidia were found in 25–35% of individuals in populations of industrialized countries and in about 65% in developing ones.
Some authors note that cryptosporidiosis is characterized by some seasonality, with a peak in morbidity in the warm season. Human infection occurs when oocysts enter, mainly through drinking water. While remaining in the environment, cryptosporidium oocysts are capable of infection for up to 18 months at 4 ° C and up to 1 week at minus 10 ° C. However, when heated (72 ° C) die for 1 min.
The main mechanism of transmission is fecal-oral. Infection can occur through direct contact with an infected person or animal, as well as with environmental objects (more often with water) contaminated with cryptosporidia.
The infective dose of cryptosporidium is very small. Thus, in the experiment it was shown that the development of infection in primates can occur even with the ingress of 10 oocysts. In healthy volunteers, the clinical picture of cryptosporidiosis developed in 100% of cases with the ingress of 1000 oocysts and in 20% with the ingestion of 30 oocysts. At the same time, mathematical modeling showed that even one oocysts can cause an infection in the gastrointestinal tract, and about 132 oocysts can cause a 50% infectious dose.
The water pathway of cryptosporidiosis, first described in 1983, is the main route of transmission of the pathogen. The greatest danger lies in the fact that most modern technologies do not allow water purification from cryptosporidiums. This is due to the unique resistance of oocysts to disinfectants, especially chlorination, as well as the small size of oocysts, which allow them to pass through many filters.
The period of the infectiousness of the source is the entire period of the disease and several weeks after the disappearance of the clinical symptoms.
Pathogenesis during Cryptosporidiosis
After the exocysting of oocysts in the stomach and duodenum, the sporozoites released from them reach the microvilli of the enterocytes, where the trophozoites formed from them further develop. The parasite invaginates the apical membrane at the base of the microvilli, which, stretching and sticking over it, form the parasitophore vacuole. With further reproduction, cryptosporidia actively contaminate the mucous membrane of the small intestine and damage its microvillous rim. The consequence of this is a violation of membrane digestion and absorption – maldigestion and malabsorption. An excessively large amount of disaccharides, peptones and other non-finally fermented substances present in the lumen of the small intestine contributes to the development of osmotic hypofermentative diarrhea. At the same time, diarrhea syndrome is maintained and the arising fermentation dyspepsia is further enhanced. The latter develops as a result of a large amount of unfermented disaccharides entering the cecum.
Adding vomiting increases fluid and electrolyte loss. In some cases, the disease can proceed without diarrhea, which is explained by the damage of the gastric mucosa by cryptosporidia.
In cryptosporidiosis, the epithelium of the pharynx, larynx, esophagus, stomach can be affected, but the epithelium of the small intestine is most often damaged. Against the background of immunodeficiency, severe forms of the disease occur, in addition to the digestive system, other organs and tissues are involved in the pathological process.
Symptoms of Cryptosporidiosis
The incubation period lasts from 4 to 14 days.
The range of clinical manifestations of cryptosporidiosis is quite wide. First of all, it depends on the immunological status of the patient. The main and most typical clinical manifestation of the disease in patients with a normal immune system and immunodeficiency states is profuse watery diarrhea.
In patients with a normal immune system, diarrhea usually develops acutely, lasts from several days to 2 weeks, after which it always goes away on its own. In contrast, patients with AIDS diarrhea develops gradually, it is harder (on average 3–6 liters per day, less often up to 20 liters per day), can last several months and often leads to patient-threatening dehydration and electrolyte disturbances. Extremely low-grade fever and flu-like syndrome such as myalgia, headache, weakness, anorexia are extremely rare in cryptosporidiosis.
While in patients with a normal immune system, the symptoms of cryptosporidiosis are limited to diarrhea, in immunodeficiency states, both intestinal and extraintestinal symptoms associated with damage to the respiratory tract, pancreas, and biliary tract can be observed.
Respiratory infection is accompanied by coughing, difficulty breathing and shortness of breath, hoarseness. However, patients do not necessarily have an intestinal lesion.
Cryptosporidiosis of the biliary tract can manifest as cholecystitis, much less often with hepatitis and sclerosing cholangitis, which is clinically manifested by fever, pain in the right hypochondrium, jaundice, nausea, vomiting and diarrhea. Bilirubin levels, alkaline phosphatase and transaminase activity may increase. Diagnosis of biliary cryptosporidiosis is based on biopsy and the detection of various stages of cryptosporidium development in the biliary tract. The defeat of cryptosporidia of the pancreas is extremely rare. Only 8 such cases have been described in HIV-infected patients.
Bronchopulmonary (respiratory) cryptosporidiosis is characterized by fever, lymphadenopathy, prolonged cough with scanty mucous, less often mucopurulent sputum, shortness of breath, cyanosis. In the sputum can be found oocysts of cryptosporidium. A biopsy reveals metaplasia of superficial epithelial cells of the bronchi. In patients with AIDS, bilateral interstitial pneumonia caused by cryptosporidia has also been described. Oocysts at the same time reveal in alveolar macrophages. Respiratory cryptosporidiosis ends with the death of patients, despite massive chemotherapy.
Diagnosis of Cryptosporidiosis
Diagnosis of cryptosporidiosis in most cases is based on the discovery of oocysts of cryptosporidium in feces and (or) much less frequently in the biopsy specimen of the small intestinal mucosa with watery diarrhea syndrome. However, the most commonly used conventional staining methods in most cases do not allow to make a diagnosis, since cryptosporidia either stains very weakly, such as during Gram staining, or stains in such a way that they cannot be distinguished from yeast-like fungi.
In this regard, most authors consider a modified (as a decolorizer instead of an alcohol – acetone mixture, 1% sulfuric acid is used) the acid resistance color is optimal for visualizing cryptosporidium. With this method of coloring, cryptosporidium oocysts are stained in red (or pink) and are clearly visible on a blue-violet background, in which other microorganisms and intestinal contents are stained. Currently, monoclonal antibodies labeled with a fluorescent label are also available, which also makes it possible to visualize this microorganism with high specificity and sensitivity.
In acute cryptosporidiosis, the number of oocysts in the feces is large. This allows direct microscopy of the faecal sample. However, in some situations, for example, in chronic cryptosporidiosis with a mild course, when the concentration of oocysts in the feces is low, it is necessary to use special techniques to increase their concentration. These include flotation methods (in solutions of sucrose by Sheaher, zinc sulfate, saturated sodium chloride solution) and concentration methods (formalin-ethyl acetate and ether formalin).
Developed serological tests – immunofluorescence and enzyme immunoassay. However, their significance for the diagnosis of active disease is extremely limited and uninformative. Therefore, these tests are used only in epidemiological studies.
Some authors recommend the use of molecular research methods, in particular, the polymerase chain reaction (PCR). However, their significance for routine laboratory diagnosis of cryptosporidiosis has not yet been determined.
Treatment of Cryptosporidiosis
Cryptosporidiosis is not treatable. However, antiretroviral drugs can reduce or stop the symptoms of this disease.
Several drugs intended for other purposes are being tested for the treatment of cryptosporidiosis. These include paromomitsin (Humatin), azithromycin (Zitromaks), latrasuril and atovakon (Mepron).
But the most promising drug in this area is nitazoxanide. He helped half of all patients who participated in the research of this drug. Unfortunately, the development of nitazoxanide was stopped due to a decision by the US Food and Drug Administration. However, in 2002, the drug was approved for the treatment of children.
It is impossible to get rid of a crypto infection. But it is possible to control the diarrhea caused by this infection. For this you can use Imodium, Kaopektat and other similar drugs. In severe cases, diarrhea is also sometimes treated with Sandostatin.
Another remedy for diarrhea caused by cryptosporidiosis, Sporidin-G, is now at the testing stage.
If you have diarrhea, pay attention to the fact that you should drink plenty of fluids to avoid dehydration.
Appointed carefully selected (with the absence of disaharov) diet, enzymes, mucoprotectors. In etiotropic therapy of immunocompetent individuals use macrolides, cotrimoxazole, daraprim, metronidazole, furazolidone. Rehydration therapy is underway.
Effective methods of etiotropic therapy of immunocompromised individuals and, especially, patients with HIV / AIDS have not yet been developed. Treatments use macrolides, clindamycin, furazolidone and other drugs. However, pathogenetic therapy and more effective treatment of the underlying disease, HIV infection, are of primary importance. However, in individuals with immunodeficiency of any nature, spiramycin (rovamycin) up to 3-9 g per day is recommended.
Prevention of Cryptosporidiosis
There are no drugs to prevent cryptosporidiosis.
The best protection is cleanliness. Avoid contact with human or animal excrement. Be sure to wash your hands after using the toilet, working in the garden, contacting dirty laundry or animals, or caring for your child (changing diapers). Cryptosporidiosis can be transmitted through saliva or sexual contact. Do not swallow water during swimming, as it may contain cryptosporidiosis bacteria. Raw oysters may also contain these bacteria.
In some cities, the public water supply can carry cryptosporidiosis bacteria. This can be found in the water department of your city. If there are bacteria in drinking water, and your CD4 cell count is below 300, try to fulfill the following conditions:
- Bring drinking water to a boil and boil for at least 1 minute, or
- Drink bottled water, or
- Drink filtered water. Use filters labeled “1-micron filter” or “conforms to the standards of the National Science Foundation,” or
- Drink distilled water, as bottled water may be unsafe if it has not been boiled or purified properly.