Strongyloides, cryptosporidium , and other parasitic infections

Epidemiology and risk factors

There are more than 40 species within the genus of Strongyloides; however, the main species that infects humans is S. stercoralis . It is an intestinal nematode predominantly present in the subtropics and tropical areas as well as in the Appalachian area and southeastern United States. It is estimated that between 30 million and 100 million people worldwide are infected with Strongyloides spp. ^, S. rhabditiform larvae are excreted in stool of infected individuals and either develop into free-living adult worms or into the filariform larvae. During the free-living adult worm stage, they can produce fertilized eggs that can then develop into the rhabditiform larvae. ^, Transmission often occurs when the filariform larvae penetrate the skin of a person walking barefoot on soil in endemic areas. Larvae then travel to the intestines and mature into adult worms. It is the only nematode that can cause autoinfection once it completes the life cycle within a human host. ^, In autoinfection, adult female worm lay eggs within the intestinal mucosa that become rhabditiform larvae. Subsequently, these larvae develop into the filariform larvae and can penetrate the intestinal mucosa or perianal skin and migrate to the intestines via the lungs to restart the cycle.

Possible outcomes to an initial infection are eradication of the infection, autoinfection, and hyperinfection or disseminated disease, which is rare in immunocompetent hosts. Transmission from human to human is extremely rare. Transmission can occur as part of SOT seen as donor-derived infections, * which is most often associated with kidney transplantation (KTx) with an increased number of hyperinfections related to corticosteroid use. ^{, ,} Infections in bone marrow transplant recipients have been rarely reported. Hyperinfection occurs during autoinfection, with an increase larval migration into the pulmonary system. In disseminated disease, larvae migrate within the venous system to reach other organs. In disseminated disease, there is an increased risk of enteric gram-negative bacteremia and meningitis. Data on Strongyloides in children being treated for cancer are not available.

The main epidemiologic risk factor for developing strongyloidiasis is living or visiting endemic areas, such as Central and South America, the Caribbean, Puerto Rico, Mexico, sub-Saharan Africa, Asia, India, and Oceania. The highest seropositivity in these areas can exceed 80% as opposed to only 3.8% in the United States, yet 6.7% of pretransplant evaluations reveal positive serology results in asymptomatic Hispanic transplant candidates.

Clinical manifestations

Most infections are asymptomatic, but strongyloidiasis can present with abdominal pain, diarrhea, bloating, anorexia, cough, sore throat, or rash in the immunocompetent patient. ^, Owing to the use of immunosuppression, including corticosteroids, SOT recipients can present with gastrointestinal symptoms, respiratory distress, sepsis-like picture, bacteremia, and/or meningitis. ^, The pathogenesis stems from autoinfection through intestinal mucosa allowing for bacterial seeding. In disseminated disease, end-organ dysfunction specific to the larval migration is seen. Eosinophilia can be present in up to 30% of patients with hyperinfection syndrome. ^{, ,} Mortality associated with hyperinfection can range from 25% to 87%, with better outcomes depending on early detection. ^{, ,} Patients have also developed acute respiratory distress syndrome as a complication of hyperinfection.

Disease prophylaxis and prevention

There are few existing guidelines suggesting the use of universal screening as it pertains to KTx programs. ^{, , ,} However, reports based on surveys show that only 10% of organ procurement organizations actually screen for Strongyloides infection. Screening is based on the presence of epidemiologic risk factors, such as traveling to or having lived in an endemic area, unexplained eosinophilia, or a history of previous Strongyloides infection. However, geographic risk is not reliable enough to serve as the primary screening tool as adult worms can live up to 5 years. More robust screening algorithms are warranted to reduce the risk of donor-derived infections along with increased screening from organ procurement organizations. Depending on geographic location, transplant programs should perform Strongyloides screening universally. The Miami Transplant Institute has recently adopted a universal prophylaxis protocol given it experience with adults in whom donor-derived Strongyloides infections developed—one with a positive serologic test result and another with a false-negative serologic test result. If a screening test result is positive, the recipient should receive prophylaxis with ivermectin to reduce the risk after transplantation. Considerations to timing for prophylaxis must include assurance of ivermectin absorption. Therefore prophylaxis can occur during the pretransplant period or soon after transplantation, depending on recipient or donor seropositivity.

Diagnosis

The gold standard for diagnosis is isolation of larvae from stool specimens. However, the sensitivity of this method remains low, ranging from 15% to 30%. Serial stool examinations can be submitted to increase the sensitivity. Based on the life cycle of this organism, larvae may not be present during the time of stool examinations. Additionally, the gastrointestinal function of the individual needs to be considered. Recently serologic testing has become more popular and has become the method of choice for screening. ^{, ,} Sensitivity varies depending on the assay performed; indirect immunofluorescence assays having the highest sensitivity. However, these are not commercially available. Sensitivity ranges from 80% up to 96% and specificity ranges from 90% up to 96%. ^, Serologic test results may remain positive even after appropriate treatment for Strongyloides infection . Experimentally, investigators have attempted to use immunoglobulin Ig A levels in saliva as an alternative, but serologic testing has higher sensitivity. Polymerase chain reaction (PCR) has been investigated as well and demonstrates potential, but it is not commercially available and the reliability needs to be evaluated in larger clinical trials. Eosinophilia may only be present in 30% of cases, but if present and unexplained, it should prompt screening immediately. An approach to risk-based screening and symptom-based diagnostic testing for Strongyloides in organ donors and organ recipients is shown in Fig. 32.1 .

Treatment

The drug of choice is ivermectin for the treatment of asymptomatic disease, hyperinfection, and disseminated disease. Treatment may be prolonged in immunocompromised patients. Prophylactic dosing is 200 μg/kg once daily for 2 days; some experts recommend repeating the dose 2 weeks apart. Albendazole is an alternative treatment for Strongyloidiasis infection for 3 to 7 days. However, some experts recommend the combination of ivermectin and albendazole in hyperinfection and disseminated disease in the SOT population. ^, Parenteral formulations are not approved and may not be available; however, the veterinary formulation may be used subcutaneously. The pediatric and adult dosing for ivermectin and albendazole is shown in Table 32.1 .

Infection prevention and anticipatory guidance

The best preventative effort to avoid infection is to wear shoes while walking on soil in endemic areas. Human-to-human transmission is extremely rare except in donor-derived infections in SOT recipients. Standard precautions such as hand hygiene after stool contact are recommended in hospitalized patients. Screening for Strongyloides infection should be performed in patients who will receive immunosuppressive therapy.

Epidemiology and risk factors

Cryptosporidium is an intracellular parasite that has become one of the leading causes of diarrheal disease worldwide. The first human Cryptosporidium infection was noted in 1976. Since that time, it has increasingly become recognized as a common cause for diarrheal disease, with the Centers for Disease Control and Prevention (CDC) estimating approximately 750,000 cases occur annually, only a fraction of which are reported. From 2001 to 2010, Cryptosporidium was the leading cause of all waterborne outbreaks of diarrheal disease in the United States. Per the CDC, Cryptosporidium -related disease hospitalizations cost $45.8 million dollars per year. Estimated Cryptosporidium seroprevalence in North America ranges from 25% to 35%. ^,

Although there are many species of Cryptosporidium , the species that most commonly infect humans are C. parvum and C. hominis , with some studies noting that C. parvum causes nearly 97% of Cryptosporidium infections ^, C. hominis primarily causes human-to-human infection, whereas C. parvum can cause both human-to-human disease and animal-to-human infection. Cattle and sheep seem to serve as the primary animal reservoirs for human disease, with animal waste contaminating ground water. ^{, ,}

Fecal-to-oral transmission occurs via contaminated drinking water, food, recreational water, and indirectly via fomites. ^{, ,} In the United States, Cryptosporidium oocysts are estimated to be in 55% to 87% of surface water tested. Individuals participating in recreational water activities are at increased risk for Cryptosporidium infection, with 90% of recreational outbreaks from 1991 to 2000 linked to swimming pools and water parks. Some studies report a seasonal increase from June to September, thought to be due to increased exposures to contaminated water via recreational activities. Exposure to contaminated drinking water has also led to many Cryptosporidium -related outbreaks; one of the largest was the 1993 Milwaukee outbreak, the in which nearly 400,000 individuals were affected. ^{, ,} As an intracellular parasite, once Cryptosporidium oocysts are ingested, they infect intestinal epithelial cells. Cryptosporidium undergoes both asexual replication, resulting in merozoites that infect neighboring epithelial cells, and sexual replication, which results in oocysts. Once excreted, oocysts are immediately infectious and can lead to autoinfection and contamination of the immediate environment. Oocysts do not reproduce outside the host. Infection can result from a very small number of oocysts; some studies note as few as 10 oocysts result in infection. With an infected individual shedding up to 10 ⁸ oocysts per day, outbreaks occur easily. ^,

Although Cryptosporidium infections affect all people, both immunocompetent and immunocompromised, children and immunosuppressed individuals are at higher risk for disease. Children 2 to 11 years old are at increased risk for person-to-person transmission, with the highest number of cases in children younger than 5 years. ^{, ,} Immunosuppressed individuals are also at increased risk for disease; one study showed Cryptosporidium spp. as the cause for 21% of diarrheal cases in SOT patients compared with only 3% of cases in the control group.