Safe living after transplantation or chemotherapy

Prevention of infections by direct contact

Children are particularly prone to infections acquired by direct contact. Frequently, children engage in behaviors that place them at risk, such as placing their hands in their nose or mouth and then touching surfaces, playing in close proximity to others, and coughing or sneezing without observing adequate etiquette. Studies have shown that hand hygiene rates among children and adolescents in schools are low, sometimes not surpassing 50%. However, interventions to improve hygiene in children can be done and have proven to be effective. Increasing handwashing compliance may involve implementation of educational strategies and creativity, especially when educating younger ones who are not knowledgeable or attentive to diseases transmitted through contact. In addition, engagement of people who interact with these children outside the hospital environment is key, especially teachers and day care workers. Social media has become a useful tool for educating children on hand hygiene practices. A myriad of videos geared toward teaching children proper hand hygiene are available online and their use is encouraged.

Many infections, including respiratory viral infections, are transmitted through direct contact. For these microbes, handwashing is the mainstay of infection prevention, particularly in the vulnerable immunocompromised host. There are no pediatric studies that address hand hygiene compliance after transplantation or in immunocompromised patients. An adult survey of lung transplant recipients focusing on safe living strategies after transplant found that the majority of patients surveyed would wash hands before eating or preparing food (87.7%); however, patients younger than 40 years of age were less likely to be compliant with safe living recommendations than older patients.

To prevent infections children should be taught and encouraged to wash hands at the following times:

• Before eating or preparing food

• During and after preparing food

• After coughing, sneezing, or blowing their nose

• After touching animals or handling pet treats

• After playing outside

• After using the toilet

• After touching garbage

Unless dealing with contact with Clostridiodes difficile or visibly soiled hands, alcohol rubs are acceptable alternatives to soap and water hand hygiene.

Percutaneous exposures may also lead to infections in children. Walking barefoot is discouraged in children after transplantation as it exposes their feet to a wide variety of hazards that may lead to infection. Organisms such as Nocardia and Alternaria and other dematiaceous fungi, commonly found in the soil, plants, and decomposing debris, can lead to infections after penetrating injuries. In countries where sanitation is not perfect, parasitic infections such as Strongyloides and cutaneous larva migrans may be acquired by walking barefoot. Warts, which may be extensive and difficult to treat in transplant recipients, may also be acquired by ambulating barefoot as the virus is ubiquitous in the environment and can penetrate through small abrasions. If children want to help with gardening chores, using protective gloves is a must to avoid injuries.

Tattoos and piercings are increasingly popular among adolescents and young adults, including immunocompromised patients. Unfortunately, many are performed by unlicensed personnel, increasing the risk of infection acquisition. Tattoos have been associated with infections with organisms such as Staphylococcus aureus, Aspergillus, and nontuberculous mycobacteria, among others. Potential transmission of HIV, hepatitis B, and hepatitis C through unsafe tattooing practices is another concern. Piercings, especially tongue piercings, have equally been implicated in the development of severe infections, such as endocarditis, cellulitis, and perichondritis. Even though few reports are available of these infections specifically occurring in transplant or immunocompromised recipients, counseling regarding the potential for infection is critical. Stilley and colleagues noted that the prevalence of tattoos and piercings in adolescent and young adult heart transplant recipients mirrored that of the general adolescent population. Of the 27 patients in their study, 26% had more than two piercings and 33% had tattoos. If body piercing or tattoos are to be obtained, timing should be discussed with the transplant physician and should be avoided until immunosuppression is more stable. In addition, these body modification practices should only be performed by licensed personnel who should be made aware of the immunocompromised status of the patient so they can observe the highest hygiene measures. Home tattoos and piercings should be avoided.

Prevention of respiratory infections

Respiratory tract infections are a significant cause or morbidity and mortality in the immunocompromised hosts. Organisms causing these infections enter the body either through direct contact with contaminated secretions (including fomites) or through inhalation of organisms in the form of aerosols or droplets. Lung transplant and hematopoietic stem cell transplant (HSCT) patients are the most vulnerable because of the high frequency of progression to pneumonia, but all organ transplant recipients are at risk of high severity, especially infants or during times of increased immunosuppression. In an attempt to reduce the transmission and prevent respiratory infections, children should exercise handwashing when in contact with secretions and follow coughing and sneezing etiquette. In periods of high immunosuppression it is prudent to avoid crowded areas. Face masks are frequently used in this population to prevent the acquisition of infections. Several trials have been conducted in community settings evaluating the effectiveness of masks in preventing respiratory infections and are summarized in a comprehensive review by MacIntyre and Chughtai. Most trials had as an endpoint the prevention of influenza in households, and face masks were often combined with hand hygiene strategies. This practice was shown to be useful if wearing the mask was initiated shortly after a case of influenza or other respiratory infection was identified in the household and if patients were compliant. If possible, the immunocompromised host should remain separated from a household contact. In addition, vaccination of patients and their households has been proven to be the best method for influenza prevention.

Molds and endemic fungi may also be acquired via inhalation. Similar to solid organ transplant (SOT) and HSCT patients, those receiving chemotherapy or tumor necrosis factor alpha inhibitors should be counseled about histoplasmosis and coccidioidomycosis. Exposure to caves, chicken coops, bird roosts, and wood piles presents risk for histoplasmosis and should be avoided if possible. For coccidioidomycosis, patients who travel or live in endemic areas should additionally avoid construction and excavation sites and stay inside during dust storms. Extrapolating from infection prevention experience at hospitals where fungal outbreaks have been reported during construction and renovation, it may be prudent to avoid construction and renovation at times of higher levels of immunosuppression.

With the legalization of cannabis in a number of countries and parts of the United States and its increased medical use, adolescents may have easier access to this drug. There are many case reports in the medical literature of HSCT and SOT recipients and cancer patients in whom Aspergillus have developed after smoking contaminated marijuana, and therefore its use should be avoided. Information suggests that baked marijuana (at 300°F for 15 minutes) may be safer.

Water safety/exposure to Cryptosporidium

Exposure to contaminated drinking and recreational waters is a common source of infections in the general population. Waterborne infections may result from ingestion, inhalation, or direct contact with contaminated water sources. Direct consumption of contaminated drinking water or inadvertent ingestion or contact with contaminated water during activities such as bathing or swimming place immunocompromised patients at risk of acquiring pathogens that cause important morbidity. In the United States, during the period ranging from 2000 to 2014, approximately 500 outbreaks occurred involving contact with treated recreational waters, such as swimming pools, sprinklers, and fountains. Centers for Disease Control and Prevention (CDC) surveillance studies also identified 42 outbreaks in 19 states in 2013 and 2014 related to drinking water; 83% were associated with public community and non-community waters.

Organisms frequently associated with contaminated water include Escherichia coli, Salmonella spp., Giardia lamblia, Ascaris lumbricoides, Pseudomonas spp., and Cryptosporidium spp. Legionella can also be transmitted but is less frequently encountered in children. Viral agents such as human noroviruses, which can cause protracted diarrhea in transplant recipients, have been associated with contaminated water sources, including private wells and contaminated drinking water ( Table 13.1 ).

Cryptosporidium infection deserves special attention as it is now considered one of the major etiologies of diarrhea in childhood and has increasingly been identified as a cause of diarrhea in transplant recipients. More than 15 species have been identified, but the majority of human infections are caused by either Cryptosporidium parvum or C. hominis . The oocysts are chlorine resistant and ingestion of a small inoculum (approximately 50 cysts) can lead to clinically significant infection. Moreover, not all water filters are capable of removing Cryptosporidium. The CDC website provides useful information on water filters. Labels stating an absolute pore size (as opposed to a nominal pore size) of 1 μm or less will filter Cryptosporidium oocysts. Similarly, filters that use reverse osmosis protect against Cryptosporidium . Manufacturers who have had their filters tested specifically against Cryptosporidium label them as National Sanitation Foundation/American National Standards Institute (NSF/ANSI) Standard 53 or 58. Several case reports and series of Cryptosporidium infections in pediatric transplant recipients have been published. Exposure to recreational waters was the most common risk factor recognized for those few reports in which a common source was identified. A pediatric cohort study of renal transplant recipients by Bandin and colleagues identified Cryptosporidium as the etiologic agent of diarrhea in 18% of the patients studied. Forty-three percent of these children had had a recent exposure to swimming pools and 14% traveled to an area with increased rates of infection. In another pediatric case reported by Hong and colleagues, a 7-year-old kidney transplant recipient with Cryptosporidium -related diarrhea had exposure to a swimming pool at a resort in the United States before the onset of symptoms. Data from a nationwide French study of Cryptosporidium infections in SOT recipients (the TRANSCRYPTO study) identified 47 SOT recipients with cryptosporidiosis over 4 years. Seven were patients younger than 15 years of age. Environmental risk factors for infections were found in 18 patients, 2 patients drank nonpotable water, 4 used recreational water, and 10 traveled to endemic areas where poor water sanitation is common. The American Society for Transplantation Infectious Disease Community of Practice and the CDC recommendations for water safety in immunocompromised patients are summarized in Table 13.2 .

Many transplant centers advocate for the consumption of bottled water. The bottled water industry is regulated by the U.S. Environmental Protection Agency and Food and Drug Administration requiring certain standards to be met. However, bottled water undergoes less scrutiny than tap water. Studies have shown that bacteria will grow in noncarbonated bottled water several days after it has been bottled and stored at room temperature. In a study of the diversity of bacteria in bottled water identified by 16S ribosomal ribonucleic acid sequences, 80% to 98% of the bacteria detected were members of the Betaproteobacteria family (Burkholderiales order). Other studies have identified gram-negative organisms such as Stenotrophomonas spp. and Pseudomonas spp., bacteria associated with severe infections in immunocompromised hosts. Outbreaks related to contaminated bottled water have also been described. Eckmanns and colleagues reported an outbreak of Pseudomonas aeruginosa in six different intensive care units in Germany linked to still bottled water. Pulsed-field gel electrophoresis of the organisms recovered in 15 infected and 4 colonized patients indicated they were identical to each other and matched the environmental sample obtained from an unopened bottled water. The outbreak was terminated by the removal of the remainder of commercial bottled waters existing in the intensive care unit. More recently, an outbreak of norovirus in Spain was also sourced to still bottled water with the detection of high norovirus GI and GII ribonucleic acid levels (10 ³ and 10 ⁴ genome copies/L) in the samples obtained.

Although bottled water has not been specifically identified as being contaminated with Cryptosporidium , its consumption does not completely eliminate the risk, especially in areas of high prevalence. Sarkar and colleagues conducted a study in a highly endemic area for Cryptosporidium with the goal of determining if a protected water source could delay infection transmission. A total of 176 children were enrolled; approximately half were given either bottled water or municipal drinking water. They found that drinking bottled water was not protective against acquisition of the organism, suggesting multiple modes of transmission. The Environmental Protection Agency encourages immunocompromised patients who want to be absolutely safe about bottled water to check the labels or to call the bottling company to inquire about the techniques used to treat the water. Water bottles labeled with any of the following terms “treated with reverse osmosis, distillation, filtration through an absolute 1-μm or smaller filter” are all considered protective against Cryptosporidium . In addition, bottled waters that are derived from rivers and lakes tend to be more contaminated than those obtained from protected well or spring water sources.

Food safety

According to the CDC, 1 in 6 Americans becomes ill every year due to the ingestion of a contaminated food product. However, the incidence of these infections in SOT recipients or children with cancer is unknown. A study by Boyle and colleagues evaluated the burden of this problem in their HSCT population including children and adults over an 11-year period and found bacterial foodborne events occurred infrequently at a rate of 1/100,000 patient days. However, when contrasted to the number of cases in the general population for the same time periods, the rate in HSCT patients was 10-fold higher than that of the general population, acknowledging that this difference was likely overestimated owing to the lack of reporting in the general population. Younger age and type of transplant may influence the adherence to safer living recommendations. For example, Jain and colleagues found that in lung transplant recipients, younger age was associated with less compliance with hand hygiene and other safer living practices, although in their study almost all patients avoided raw or undercooked meat, poultry, and unpasteurized dairy products. In a small study examining the knowledge and perceptions of food safety in transplant recipients, HSCT patients were more knowledgeable than the SOT patients surveyed and expressed more willingness to adhere to recommendations. In this study, SOT patients viewed themselves as “healthy” more often than HSCT patients after transplantation and found less need to be compliant with safety recommendations.

In addition to transplant recipients (hematopoietic or solid organ) and patients receiving chemotherapy, patients receiving biological agents for the treatment of conditions such as rheumatoid arthritis and Crohn disease are also vulnerable to foodborne pathogens. For example, patients on tumor necrosis factor alpha inhibitors are at increased risk for acquiring infections with foodborne organisms such as Listeria spp. and Salmonella spp.

Although hepatitis A virus (HAV) has long been recognized as a potential contaminant of foods, other viruses such as norovirus and hepatitis E virus (HEV) have been more recently recognized as potential foodborne infections that can threaten the transplant population. Norovirus has become the leading cause of foodborne illness in the United States, with 58% of cases caused by this organism. This organism has been increasingly reported as a cause of chronic diarrhea in the adult and pediatric transplant population, as previously mentioned. Leafy green vegetables, fresh fruits, and shellfish have been commonly linked to outbreaks, and food service workers are the most common sources of infection. HEV is also transmitted via the fecal-oral route and is suspected to be a zoonosis as strains of this virus are prevalent in wild boars and swine. Kamar and colleagues reported on 14 adult patients from France in whom acute HEV developed several years after transplantation. The infection evolved into chronic hepatitis in 57% of the patients. The testing for this virus was prompted by an increased number of cases in normal hosts in the southwest region of France at the time of presentation. Subsequently, researchers from Canada demonstrated the occurrence of such infection in children after liver transplant. A child in this study who lived in semirural area of Quebec had an HEV infection with serotype 3a, a strain that shares similarities with the swine HEV 3a strain, suggesting that a zoonotic transmission likely occurred in this child. These reports highlight the importance of transplant recipients from abstaining from consuming raw or undercooked meat products. HAV risk is diminished significantly by vaccination, but caution is still needed as outbreaks continue to occur nationally and internationally

Immunocompromised patients should follow basic food safety handling recommendations by the U.S. Department of Agriculture when shopping, preparing, and storing food. The four steps for Food Safe Families are as follows:

• Clean: Wash hands and surfaces frequently.

• Separate: Do not cross-contaminate foods.

• Cook: Always cook to the correct temperature.

• Chill: Refrigerate products promptly.

Eating the following products places patients at risk of a foodborne infection and should be avoided:

• 1.

  Unpasteurized milk, fruit, or vegetable juice/cider or cheeses made from unpasteurized milk: E. coli O157:H7, Salmonella spp., Brucella , Listeria , Yersinia enterocolitica, and Cryptosporidium .

• 2.

  Raw or undercooked eggs: Salmonella spp.

• 3.

  Raw dough: Children often are allowed to play with and eat raw dough that is intended to be cooked or to be craft dough. These may be harmful as flour can be contaminated with organisms such as Salmonella spp. and E. coli .

• 4.

  Raw or undercooked meat, poultry or fish: In addition to any bacterial contamination, parasitic infections such as Taxoplasma gondii and tapeworms and viruses such as HEV may also be acquired by consuming these raw food products . De novo toxoplasmosis is of particular concern in seronegative transplant recipients, particularly in areas where the disease is endemic.

• 5.

  Raw or undercooked seafood (oysters, clams, mussels): Vibrio spp., HAV, HEV, Cryptosporidium spp ., Campylobacter jejuni.

Comprehensive recommendations, including a printable resource for transplant recipients, are available at the U.S. Department of Health and Human Services at https://www.fda.gov/food/foodborneillnesscontaminants/peopleatrisk/ucm312570.htm .

Probiotics have been increasingly used by the general population and parents often ask about their use in the immunocompromised population. In a recent trial of Lactobacillus plantarum given to children and adolescents undergoing HSCT, no cases of bacteremia or other adverse effects were documented. The Lactobacillus was administered orally starting at day −7 of transplant and continued to day +14 after transplantation. However, multiple case reports of sepsis, bacteremia, and endocarditis linked to the use of probiotics have been reported. Most of these infections have occurred in immunocompromised patients, patients with intestinal insufficiency syndrome or valvular heart disease, and in patients with central venous catheters. At this time, until further information is available regarding the safety of these products in the immunocompromised population, they should generally be avoided unless participating in a clinical trial.