Cryptosporidiosis: Diving to the heart of an emerging infection

Cryptosporidiosis, a parasitic disease caused by the protozoan Cryptosporidium, is attracting increasing medical attention due to its growing prevalence and public health consequences. This microorganism, present in the environment and often transmitted through contaminated water, can infect humans and animals, causing a range of gastrointestinal symptoms from mild to severe.

What is the infectious agent?

Cryptosporidiosis is caused by Cryptosporidium, a monoxenous protozoan that develops in the intestine of various vertebrates, including humans. Its life cycle involves asexual and sexual multiplication, resulting in the formation ofoocysts . These are excreted into the environment. They remain infectious from the moment they are released.

Cryptosporidium parvum, a parasite belonging to the Coccidia group, is responsible for cryptosporidiosis, a parasitic disease affecting humans and many animal species. Transmission from animals to humans is mainly attributed to genotype 2 of this protozoan parasite.

The thick-walled eggs of Cryptosporidium, found in swimming pools, jacuzzis, water parks, lakes and rivers, are exceptionally hardy. They are resistant to freezing conditions and to the usual levels of chlorine used in water purification.

Discovered in the early 20th century, Cryptosporidium became a major focus of interest in human pathology in the 1980s. This is due to its link with HIV/AIDS and water-related epidemics. The disinfectants commonly used in the water industry are not effective against infectious Cryptosporidium oocysts. This encourages its spread in the environment.

More than 150 species of mammals, as well as various birds, reptiles, fish and amphibians, have been identified as Cryptosporidium hosts. However, the precise classification of species remains a matter of debate due to the lack of distinctive morphological criteria and the previous concept of close specificity between species.

Molecular characterisation and genotyping of strains are essential for understanding the genetic diversity of Cryptosporidium and its transmission in the environment. This will also enable us to better trace the sources of infection and develop effective prevention strategies against this emerging parasitic infection.

How does the disease appear in animals?

Domestic and wild mammals can be potential hosts for Cryptosporidium parvum, a protozoan parasite. Among domestic mammals, cattle, sheep and goats are the most frequently affected. Among wild mammals, deer are often infected. The geographical distribution of this infection is worldwide, but its frequency varies according to region and animal population.

Young calves and kids less than three weeks old are particularly susceptible. Adult animals are generally asymptomatic, while young animals often present symptoms, mainly diarrhoea. This diarrhoea can be severe, especially when associated with other pathogens such as bacteria or viruses.

The symptoms observed in young animals vary depending on the species:

• Piglets less than 15 days old may present with abundant yellowish liquid diarrhoea, weight loss and vomiting. These symptoms can lead to severe dehydration.
• Calves may suffer from severe diarrhoea accompanied by intense weakness, which can compromise their growth and development.
• Infected poults and chicks may show signs ofrespiratory infection, such as sneezing or wheezing.
• In reptiles, the presence of Cryptosporidium parvum can lead to gastrointestinal problems such as regurgitation after meals.

The variability of the symptoms observed and their severity often depend on a number of factors, including the age of the animal, its general state of health, as well as the parasite load and the possible presence of other infections. Appropriate environmental management and hygiene practices can help to reduce the prevalence of Cryptosporidium parvum infection in animal species.

What is the mode of transmission?

Cryptosporidium parvum is transmitted to animals by ingestion ofoocysts. These are microscopic elements present in the excrement of infected animals, mainly when they suffer from diarrhoea. Transmission can continue for several months from contaminated equipment, soil, plants and water. This is because the parasite is extremely resistant. Domestic animals such as calves, lambs, kids, piglets, foals and reptiles are often carriers of Cryptosporidium parvum.

In humans, Cryptosporidium parvum is transmitted mainly via the digestive tract. This can occur through theingestion of contaminated water, whether for drinking or bathing, as well as through the consumption of contaminated raw foods, such as vegetables and fruit. Direct contact with hands soiled by infected materials is also a risk of transmission. Contagion can also occur from person to person via the faecal-oral route, for example by failing to wash one’s hands after changing the nappy of an infected child.

Cryptosporidiosis is a faeco-oral transmission disease, whereingestion of a relatively small quantity of oocysts can cause infection. The oocysts are directly infectious as soon as they are released and remain extremely resistant in the environment for over a year. As a result, this parasitosis can be spread not only by direct contact with infected individuals or animals, but also indirectly through water and food contaminated with oocysts of animal or human origin.

Transmission of Cryptosporidium parvum can be sporadic or epidemic, and presents a significant risk to public health, particularly in regions where access to clean water and adequate hygiene practices is limited.

What does the disease look like in humans?

The incidence of cryptosporidiosis is worldwide, although little is known about the situation outside of water-related epidemics. Professional activities involving contact with animals, their faeces or their contaminated environment present an increased risk of infection.

The symptoms of cryptosporidiosis can take three forms. Some people may be asymptomatic. Others may experience diarrhoea, abdominal cramps, fever and fatigue for one to two weeks, with the possibility of relapses. In severely immunocompromised people, severe forms can lead to dehydration.

Symptoms of cryptosporidiosis usually appear abruptly about 7 days after infection, with abdominal cramps and watery diarrhoea. Other symptoms include nausea, vomiting, loss of appetite, fever and general weakness. In immunocompromised patients, symptoms may develop gradually. Diarrhoea can amount to 11 to 15 litres of liquid stools per day in AIDS patients.

Cryptosporidiosis is also associated with undernutrition in children living in precarious sanitary conditions, leading to disruption of intestinal function and poor absorption of nutrients. In immunocompetent individuals, symptoms include:

• profuse diarrhoea
• abdominal pain
• nausea
• low-grade fever.

The illness lasts from three to fourteen days. For the elderly and children, the diarrhoea may be prolonged.

In immunocompromised patients, diarrhoea may become chronic and persistent. This is life-threatening, especially if the immunosuppression is not corrected. However, the use of antiretroviral therapies has led to a significant reduction in the number of cases of cryptosporidiosis in HIV-infected patients in countries that benefit from these treatments.

How is it diagnosed?

Diagnosis of cryptosporidiosis is based on stool analysis. Several approaches are used to detect the presence of the Cryptosporidium parasite in a stool sample.

The first method involves looking for a protein released by the parasites (parasite antigen) or their genetic material (DNA) in the stool sample. Another approach involves direct microscopic examination of the stools to identify Cryptosporidium eggs. However, this method is less sensitive and may require the collection of several stool samples to detect the parasite.

In cases where diagnostic stool examinations fail to identify the cause of persistent diarrhoea, doctors can use a flexible observation tube (endoscope) to examine the upper part of the digestive tract, particularly the duodenum. This procedure may yield a tissue sample for analysis (biopsy), in which the presence of Cryptosporidium may be observed.

PCR (polymerase chain reaction) diagnosis is considered to be the reference method for diagnosing cryptosporidiosis. This technique amplifies the parasitic DNA in stools or intestinal biopsies, offering excellent sensitivity and specificity. It can also be used to identify the different pathogenic species and genotypes of the parasite after sequencing the amplicons.

Other diagnostic methods include :

• microscopic examination of stools for Cryptosporidium oocysts,
• detection of parasitic copro-antigens using the Elisa method
• immunochromatographic rapid diagnostic tests (RDTs),
• immunofluorescence techniques to identify oocysts using specific antibodies.

In addition, quantitative duplex PCR can be used to search for Cryptosporidium DNA. This allows detection, quantification of the parasite load and molecular identification of the species. These molecular techniques are mainly performed in specialist or reference laboratories.

How is this protozoan infection treated?

Treatment of cryptosporidiosis varies according to the patient’s immune status and the severity of symptoms. For immunocompetent individuals with severe or persistent diarrhoea, nitazoxanide is generally prescribed. In AIDS patients, priority is given to treatment of HIV infection. Nitazoxanide is sometimes added to relieve symptoms.

In the event of severe diarrhoea, rehydration solutions and anti-diarrhoeal drugs may be recommended. Most immunocompetent people recover spontaneously. Nitazoxanide can speed up the healing process in cases of persistent or severe diarrhoea.

It is important to note that nitazoxanide does not cure cryptosporidiosis in people with AIDS. However, it can help to reduce symptoms. In some cases, doctors may also consider using paromomycin or a combination of paromomycin and azithromycin to reduce symptoms in these patients.

It is not clear whether nitazoxanide is effective in people with immune deficiency due to other factors, but it may be useful in some cases. Management of severe diarrhoea may require oral or intravenous rehydration and antidiarrhoeal agents such as loperamide. However, loperamide is not recommended in AIDS patients.

There is currently no curative treatment for cryptosporidiosis. However, certain antibiotics of the rifamycin class may help to reduce symptoms.

Nitazoxanide is the main drug used to treat immunocompetent patients, demonstrating clinical efficacy in several studies. However, in immunocompromised patients, its efficacy remains limited. Reconstitution of immunity remains crucial for complete elimination of the parasite. Other drugs such as paromomycin and azithromycin may also be considered in certain situations.

What are the means of prevention?

Prevention of cryptosporidiosis is based on appropriate sanitary measures and rigorous hygiene, particularly in livestock farms and exposed workplaces. Here is an overview of the main measures recommended:

• General farm hygiene: This includes regular cleaning and disinfection of premises and equipment. Appropriate storage of waste and animal carcasses is also required.
• Employee training and information: Employees must be made aware of the risks associated with cryptosporidiosis, as well as individual and collective preventive measures.
• Provision ofappropriate resources: Ensure access to drinking water, soap, disposable wiping materials and a first-aid kit defined in collaboration with the occupational physician.
• Compliance with hygiene rules: This includes frequent hand-washing with drinking water and soap, particularly after any contact with animals, waste or excrement, and before meals and breaks.
• Reinforcing hygiene in the event of animal disease: Additional measures must be taken if animal diseases are detected. These measures include curative treatment, limiting access to essential professionals and washing/disinfecting contaminated sites and equipment.
• Reducing sources of contamination: Avoid using high-pressure water jets to clean up animal waste, and wear gloves when handling cadavers or animal waste. People with weakened immune systems are strongly advised not to come into contact with animals suffering from diarrhoea.
• Individual and collective prevention: As well as complying with individual hygiene rules, collective actions such as controlling environmental contamination and protecting water resources intended for human consumption are essential.

The prevention of cryptosporidiosis is based on a multidimensional approach involving strict sanitary measures, appropriate awareness-raising and continuous monitoring to reduce the risks of contamination and transmission of this disease.

Some epidemiological data…

Cryptosporidiosis is a cosmopolitan parasitic infection caused by parasites of the genus Cryptosporidium. Although cryptosporidiosis is not considered a contagious animal disease and is not subject to mandatory public health reporting (except for collective food poisoning), it remains a significant public health problem, particularly in developing countries with poor sanitary conditions.

In the United States, cryptosporidiosis has been responsible for several epidemics of diarrhoea. These include the outbreak in Baker City, Oregon, where almost 2,780 people fell ill in 2013 after Cryptosporidium contaminated the city’s water supply. Similar epidemics have been observed in other towns and nurseries. In France, despite the absence of any reporting obligation, several epidemics have been reported. They were mainly linked to faecal contamination of drinking water systems.

The prevalence of the disease varies considerably between industrialised and developing countries, with infection rates ranging from 0.6% to 2% in industrialised countries compared with 4% to 32% in developing countries. People living with HIV are at increased risk of infection, with prevalence rates ranging from 3% to 20% in the United States to 50% to 60% in Africa and Haiti.

The genus of Cryptosporidium most commonly associated with cryptosporidiosis varies according to geographical region. In Europe, Cryptosporidium parvum is often responsible for the majority of infections. In the United States, Canada, Australia and Japan, it is more often Cryptosporidium hominis.

There are also seasonal variations in the incidence of the disease. Annual peaks occur in spring and autumn in many countries. In France, since 2001, there has been a reduction in the number of cases in the spring following changes in the regulations governing water distribution.