Diarrhea after kidney transplantation: A study of risk factors and outcomes.

Background: Diarrhea in kidney transplant recipients (KTRs) can be associated with significant morbidity. Material and Methods: We evaluated 198 KTRs for a history of diarrhea post-kidney transplant at a tertiary care center in western India over 1 year. A protocol-based evaluation of diarrhea was done with respect to clinical features, diagnostic evaluation, associated acute allograft dysfunction, and its impact on long-term allograft function. Primary outcomes of interest were: chronic allograft injury (CAI) and the need for mycophenolate mofetil (MMF) withdrawal. We also assessed the effect of MMF withdrawal on the risk of the development of CAI. Results: Eighty-five of 198 (42.5%) recipients experienced diarrhea and a total of 140 diarrheal episodes were evaluated. The mean age of these 85 recipients was 38 ± 12 years and 72 (84.7%) were males. 73 of 85 recipients were on MMF at the time of diarrhea and in 35 (48%) of them MMF withdrawal was needed for chronic and persistent symptoms. Diarrhea was attributed to infective etiologies in 90 of 140 (64.2%) cases. Among the microbiologically confirmed infective diarrheal episodes, giardia and cryptosporidium were the common pathogens in 11/28 (39%) and 6/28 (21.4%) episodes respectively. One hundred and twenty-eight episodes out of 140 (91.4%) episodes were complicated by acute allograft dysfunction. Forty-one of 85 recipients (48.2%) developed chronic allograft injury and 12 (14.1%) developed allograft rejection (acute and/or chronic). Probability of chronic allograft injury was higher in those with MMF withdrawal. Conclusion: Diarrhea post-kidney transplant adversely affects graft function, especially after MMF withdrawal.

Epidemiology of Cryptosporidiosis, New York City, New York, USA, 1995-20181.

Cryptosporidiosis is a parasitic diarrheal infection that is transmitted by the fecal-oral route. We assessed trends in incidence and demographic characteristics for the 3,984 cases diagnosed during 1995-2018 in New York City, New York, USA, and reported to the New York City Department of Health and Mental Hygiene. Reported cryptosporidiosis incidence decreased with HIV/AIDS treatment rollout in the mid-1990s, but the introduction of syndromic multiplex diagnostic panels in 2015 led to a major increase in incidence and to a shift in the demographic profile of reported patients. Incidence was highest among men 20-59 years of age, who consistently represented most (54%) reported patients. In addition, 30% of interviewed patients reported recent international travel. The burden of cryptosporidiosis in New York City is probably highest among men who have sex with men. Prevention messaging is warranted for men who have sex with men and their healthcare providers, as well as for international travelers.

Cryptosporidiosis among solid organ transplant recipient attendees at a summer camp.

We report a cluster of pediatric cryptosporidiosis infections among solid organ transplant recipients at a summer camp in Georgia, USA. A retrospective cohort study was conducted to investigate the risk factors for infection. A total of 118 campers attended the camp during July 23-28, 2017. The overall attack rate among campers during the outbreak was 11% (13/118). Sanger-based amplicon sequencing of stool specimens from 7 (80%) campers identified Cryptosporidium hominis as the suspected etiologic agent. All infected campers were heart or kidney transplant recipients receiving immunosuppressive therapy. The median reported symptom duration was 12 days (range 6-18 days) and 9 (69.2%) were hospitalized for at least one night (median length of stay 5 days, range 2-16 days). There were no deaths or acute rejection events attributed to infection. The results of the epidemiologic and environmental investigation suggest a recreational pool as the presumed source, although there was no direct evidence to support this. Many long-term interventions were implemented, and there have been no further outbreaks at the camp in the following two years. This outbreak demonstrates that cryptosporidiosis may be associated with notable burden in pediatric transplant recipients, and illustrates the challenges associated with source identification and containment.

Intestinal parasites including Cryptosporidium, Cyclospora, Giardia, and Microsporidia, Entamoeba histolytica, Strongyloides, Schistosomiasis, and Echinococcus: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of intestinal parasites in the pre- and post-transplant period. Intestinal parasites are prevalent in the developing regions of the world. With increasing travel to and from endemic regions, changing immigration patterns, and the expansion of transplant medicine in developing countries, they are increasingly recognized as a source of morbidity and mortality in solid-organ transplant recipients. Parasitic infections may be acquired from the donor allograft, from reactivation, or from de novo acquisition post-transplantation. Gastrointestinal multiplex assays have been developed; some of the panels include testing for Cryptosporidium, Cyclospora, Entamoeba histolytica, and Giardia, and the performance is comparable to conventional methods. A polymerase chain reaction test, not yet widely available, has also been developed to detect Strongyloides in stool samples. New recommendations have been developed to minimize the risk of Strongyloides donor-derived events. Deceased donors with epidemiological risk factors should be screened for Strongyloides and recipients treated if positive as soon as the results are available. New therapeutic agents and studies addressing the optimal treatment regimen for solid-organ transplant recipients are unmet needs.

Amixicile Reduces Severity of Cryptosporidiosis but Does Not Have In Vitro Activity against Cryptosporidium.

Cryptosporidium species cause significant morbidity in malnourished children. Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ has diminished effectiveness during malnutrition. Here, we show that amixicile, a highly selective water-soluble derivative of NTZ diminishes Cryptosporidium infection severity in a malnourished mouse model despite a lack of direct anticryptosporidial activity. We suggest that amixicile, by tamping down anaerobes associated with intestinal inflammation, reverses weight loss and indirectly mitigates infection-associated pathology.

Case Report: A Cryptosporidium infection in a patient with relapsed T-lymphoblastic lymphoma undergoing allogeneic stem cell transplantation.

Cryptosporidium infection is a rare cause of enterocolitis. In immunocompromised patients, cryptosporidiosis may lead to debilitating and life-threatening diarrhea and malabsorption, occasionally with multi-organ involvement. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) requires long-term immunosuppressive therapy, while cellular immunity is usually compromised due to intensive conditioning chemotherapy. Diarrhea in patients who underwent allo-HSCT may be a sign of an infection, but can also be the result of intestinal graft-versus-host disease (GvHD). Here, we describe the case of a patient who developed severe diarrhea following allo-HSCT for relapsed T-lymphoblastic lymphoma. Initially, GvHD was suspected and treatment was initiated accordingly. However, a colon biopsy showed signs of cryptosporide oocysts alongside only low-grade GvHD. Following molecular confirmation of the diagnosis of cryptosporidiosis, an intensive treatment regimen was started. Despite the severe clinical course, the patient recovered and was discharged with only residual symptoms.

Symptoms and risk factors of Cryptosporidium hominis infection in children: data from a large waterborne outbreak in Sweden.

Cryptosporidium is a major cause of diarrheal disease worldwide. In developing countries, this infection is endemic and in children, associated with growth faltering and cognitive function deficits, with the most severe impact on those aged <2 years. Little has been reported about symptoms and risk factors for children in industrialized countries, although the disease incidence is increasing in such regions. In November 2010, a large waterborne outbreak of C. hominis occurred in the city of Östersund in Sweden. Approximately 27,000 of the 60,000 inhabitants were symptomatic. We aimed to describe duration of symptoms and the risk factors for infection with C. hominis in children aged <15 years in a Western setting. Within 2 months after a boil water advisory, a questionnaire was sent to randomly selected inhabitants of all ages, including 753 children aged <15 years. Those with ≥3 loose stools/day were defined as cases of diarrhoea. The response rate was 70.3%, and 211 children (39.9%) fulfilled the case definition. Mean duration of diarrhoea was 7.5 days (median 6, range 1-80 days). Recurrence, defined as a new episode of diarrhoea after ≥2 days of normal stools, occurred in 52.5% of the cases. Significant risk factors for infection, besides living within the distribution area of the contaminated water plant, included a high level of water consumption, male sex, and a previous history of loose stools. The outbreak was characterized by high attack and recurrence rates, emphasizing the necessity of water surveillance to prevent future outbreaks.

Cryptosporidiosis Outbreak Associated With a Single Hotel.

We investigated a gastrointestinal illness cluster among persons who attended a baseball tournament (>200 teams) during July 2015. We interviewed representatives of 19 teams; illness was reported among only the 9 (47%) teams that stayed at Hotel A (p < .01). We identified 55 primary cases. A case-control study demonstrated that pool exposure at Hotel A was significantly associated with illness (odds ratio: 7.3; 95% confidence interval: 3.6, 15.2). Eight out of nine (89%) stool specimens tested were positive for Cryptosporidium, with C. hominis IfA12G1 subtype identified in two specimens. The environmental health assessment detected a low free available chlorine level, and pool water tested positive for E. coli and total coliforms. A possible diarrheal contamination event, substantial hotel pool use, and use of cyanuric acid might have contributed to this outbreak and magnitude. Aquatic facilities practicing proper operation and maintenance (e.g., following the Centers for Disease Control and Prevention's Model Aquatic Health Code) can protect the public's health.

Allograft biopsy findings in patients with small bowel transplantation.

In this study, we sought to determine the incidence of post-transplant complications including acute cellular rejection (ACR), infection, and post-transplant lymphoproliferative disease (PTLD) in mucosal allograft biopsies in patients with small bowel transplant at our institution. We retrospectively reviewed pathology reports from 5675 small bowel allograft biopsies from 99 patients and analyzed the following: indications for biopsy, frequency and grade of ACR, the presence of infectious agents, results of workup for potential PTLD, results of C4d immunohistochemistry (IHC), features of chronic mucosal injury, and findings in concurrent native bowel biopsies. Findings from 42 allograft resection specimens were also correlated with prior biopsy findings. Indeterminate, mild, moderate, and severe ACR were seen in 276 (4.9%), 409 (7.2%), 100 (1.8%), and 207 (3.6%) of biopsies, respectively. Although ACR may show histologic overlap with mycophenolate mofetil toxicity, we found the analysis of concurrent native bowel biopsies to be helpful in this distinction. Adenovirus was the most common infectious agent seen (11%), and we routinely performed adenovirus IHC on biopsies. Eighteen patients (18%) developed PTLD, 83% of which were EBV associated, but only 28% of PTLD cases were diagnosed on mucosal allograft biopsies. C4d IHC did not correlate with the presence of donor-specific antibodies in limited cases.

Febrile neutropenia and refeeding syndrome.

We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues.

Multiple Simultaneous Gastrointestinal Parasitic Infections in a Patient with Human Immunodeficiency Virus.

Patients with the human immunodeficiency virus (HIV) infection are at high risk for gastrointestinal infections causing diarrhea, particularly when those infections are parasitic in nature. This propensity is more pronounced in AIDS, where opportunistic parasitic infections may cause severe diarrhea, marked absorptive dysfunction, and significant risk of mortality. There are scant data regarding parasitic infections among HIV patients in the developed world; most studies and research come from povertystricken areas of South Africa, India, Iran, and the South Pacific. Although multiple infections with the same or different parasites have been reported, simultaneous infections are rare. We present the case of a 35-year-old man who developed a co-infection with Giardia, Cryptosporidium, and Strongyloides, simultaneously, the diagnosis being made after the judicious evaluation of a stool sample. Given the associated morbidity, prompt diagnosis and treatment are needed to avoid further complications in patients with HIV. To our knowledge this is the first reported case of triple parasitic infection in a patient with HIV.

Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience.

BACKGROUND: X-linked hyper-IgM syndrome (X-HIGM) due to mutations in the gene encoding CD40 ligand results in failure of Ig class switching and an increased propensity for recurrent sinopulmonary and other infections, and thus decreased life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is curative, but long-term follow-up data are limited. PROCEDURES: We conducted a retrospective analysis of seven patients who have undergone allogeneic HSCT for HIGM syndrome at Duke University Medical Center. RESULTS: Median age at transplant was 5.2 years (range 0.7-19.3). None of the patients had active hepatic or pulmonary disease immediately prior to transplant, but all had a history of serious infections. Five patients received myeloablative conditioning, and two patients received reduced intensity conditioning. Graft sources included bone marrow, peripheral blood, and unrelated umbilical cord blood. Post-transplantation complications included veno-occlusive disease, hemorrhagic cystitis, adenoviremia, and cryptosporidium recurrence in one patient each. Two patients developed acute GVHD grades II-IV that resolved promptly with treatment and none developed extensive chronic GVHD. All patients are intravenous IgG-independent and 6/7 have normal antibody titers. Immunoglobulin (Ig) A levels normalized in all but one patient and T and B cell numbers and function are otherwise normal in all. All patients are alive at a median follow-up of 9.7 (range 9.7-16.1) years post-transplantation with predominantly donor chimerism and no recurrent infections. CONCLUSIONS: Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.

Aetiology and epidemiology of human cryptosporidiosis cases in Galicia (NW Spain), 2000-2008.

Cryptosporidium infects millions of people worldwide causing acute gastroenteritis, but despite its remarkable epidemiological and economic impact, information on the epidemiological trends of human cryptosporidiosis is still scarce in most countries. Here we investigate a panel of 486 cases collected in Galicia (NW Iberian Peninsula) between 2000 and 2008, which sheds new light on the epidemiology in this region of the South Atlantic European façade. Incidence rates in Galicia are one order of magnitude higher than those reported in other regions of Spain, suggesting that this parasite remains largely underdiagnosed in this country, and are also larger than those typical of other European countries with available data. Two species dominate our dataset, Cryptosporidium hominis (65%) and C. parvum (34%). The sex ratio of patients infected by either species was 0·5, but C. hominis was significantly more common in younger males. C. parvum infections were more acute and required more specialized medical attention, which suggests a differential adaptation of each species to human hosts. The parasites display strong seasonal and geographical variation. C. parvum incidence peaked during summer and was mainly detected in rural areas while C. hominis infections were more frequent in autumn and exhibited a more even geographical distribution. Such differences probably reflect their distinct sources of infection - C. parvum is mainly zoonotic and C. hominis anthroponotic - and the effects of climatic variables, like temperature and rainfall.

Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses.

Cryptosporidium infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure. Cryptosporidium parvum virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by Cryptosporidium spp. Here we show that intestinal epithelial conditional Ifnar1-/- mice (deficient in type I IFN receptor) are resistant to C. parvum infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas C. parvum infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvum defense and Cryptosporidium uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.

Multi-pathogen waterborne disease outbreak associated with a dinner cruise on Lake Michigan.

We report an outbreak associated with a dinner cruise on Lake Michigan. This took place on the same day as heavy rainfall, which resulted in 42·4 billion liters of rainwater and storm runoff containing highly diluted sewage being released into the lake. Of 72 cruise participants, 41 (57%) reported gastroenteritis. Stool specimens were positive for Shigella sonnei (n=3), Giardia (n=3), and Cryptosporidium (n=2). Ice consumption was associated with illness (risk ratio 2·2, P=0·011). S. sonnei was isolated from a swab obtained from the one of the boat's ice bins. Environmental inspection revealed conditions and equipment that could have contributed to lake water contaminating the hose used to load potable water onto the boat. Knowledge of water holding and distribution systems on boats, and of potential risks associated with flooding and the release of diluted sewage into large bodies of water, is crucial for public health guidance regarding recreational cruises.

The epidemiology of sporadic human infections with unusual cryptosporidia detected during routine typing in England and Wales, 2000-2008.

Routine typing of 14 469 isolates from human cryptosporidiosis cases between 2000 and 2008 revealed that 7439 (51·4%) were Cryptosporidium (C.) hominis, 6372 (44·0%) C. parvum, 51 (0·4%) both C. hominis and C. parvum, 443 (3·1%) were not typable and 164 (1·1%) were other Cryptosporidium species or genotypes. Of the latter, 109 were C. meleagridis, 38 C. felis, 11 C. ubiquitum, one C. canis, two horse, two novel and one skunk genotype. C. hominis monkey genotype and C. cuniculus were identified in a separate study. Patients with unusual infections were older than those with C. hominis (P<0·01) or C. parvum (P<0·01) and were more likely to be immunocompromised (Fisher's exact P<0·01). Forty-one percent of unusual cases had travelled abroad, mainly to the Indian subcontinent. Significant risk factors in those with unusual species were travel abroad (C. meleagridis, P<0·01), being immunocompromised (C. felis, Fisher's exact P=0·02), and contact with cats (C. felis, Fisher's exact P=0·02).

Cryptosporidium enteritis in solid organ transplant recipients: multicenter retrospective evaluation of 10 cases reveals an association with elevated tacrolimus concentrations.

BACKGROUND: Cryptosporidial enteritis, a diarrheal infection of the small intestine caused by the apicomplexan protozoa Cryptosporidium, is infrequently recognized in transplant recipients from developed countries. METHODS: A retrospective review of all cases of cryptosporidiosis in solid organ transplant (SOT) recipients at 2 centers from January 2001 to October 2010 was performed and compared with transplant recipients with community-onset Clostridium difficile infection (CDI). A literature search was performed with regard to reported cases of cryptosporidiosis in SOT recipients. RESULTS: Eight renal, 1 liver, and 1 lung transplant recipient were diagnosed with cryptosporidiosis at median 46.0 months (interquartile range [IQR] 25.2-62.8) following SOT. Symptoms existed for a median 14 days (IQR 10.5-14.8) before diagnosis. For the 9 patients receiving tacrolimus (TAC), mean TAC levels increased from 6.3 ± 1.1 to 21.3 ± 9.2 ng/mL (P = 0.0007) and median serum creatinine increased temporarily from 1.3 (IQR 1.1-1.7) to 2.4 (IQR 2.0-4.6) mg/dL (P = 0.008). By comparison, 8 SOT recipients (6 kidney, 2 liver) hospitalized with community-onset CDI had a mean TAC level of 10.8 ± 2.8 ng/dL during disease compared with 9.2 ± 2.3 ng/mL at baseline (P = 0.07) and had no change in median creatinine. All patients recovered from Cryptosporidium enteritis after receiving various chemotherapeutic regimens. CONCLUSIONS: Cryptosporidiosis should be recognized as an important cause of diarrhea after SOT and is associated with elevated TAC levels and acute kidney injury. Increased TAC levels may reflect altered drug metabolism in the small intestine.

Cryptosporidiosis: a rare and severe infection in a pediatric renal transplant recipient.

Cryptosporidium is an intracellular protozoan parasite that causes gastroenteritis in human. In immunocompromised individuals, cryptosporidium causes far more serious disease. There is no effective specific therapy for cryptosporidiosis, and spontaneous recovery is the rule in healthy individuals. However, immunocompromised patients need effective and prolonged therapy. Here, we present our clinical experience in a six-yr-old boy who underwent living-related donor renal transplantation and who was infected with Cryptosporidium spp. Our patient was successfully treated with antimicrobial agents consisting of spiramycin, nitazoxanide, and paromomycin. At the end of second week of therapy, his stool became negative for Cryptosporidium spp. antigen and spiramycin was discontinued. Nitazoxanide and paromomycin treatment was extended to four wk. With this case, we want to emphasize that cryptosporidiosis should be considered in the differential diagnosis of severe or persistent diarrhea in solid organ transplant recipients where rigorous antimicrobial therapy is needed.

Participatory probabilistic assessment of the risk to human health associated with cryptosporidiosis from urban dairying in Dagoretti, Nairobi, Kenya.

We carried out a participatory risk assessment to estimate the risk (negative consequences and their likelihood) from zoonotic Cryptosporidium originating in dairy farms in urban Dagoretti, Nairobi to dairy farm households and their neighbours. We selected 20 households at high risk for Cryptosporidium from a larger sample of 300 dairy households in Dagoretti based on risk factors present. We then conducted a participatory mapping of the flow of the hazard from its origin (cattle) to human potential victims. This showed three main exposure pathways (food and water borne, occupational and recreational). This was used to develop a fault tree model which we parameterised using information from the study and literature. A stochastic simulation was used to estimate the probability of exposure to zoonotic cryptosporidiosis originating from urban dairying. Around 6 % of environmental samples were positive for Cryptosporidium. Probability of exposure to Cryptosporidium from dairy cattle ranged from 0.0055 for people with clinical acquired immunodeficiency syndrome in non-dairy households to 0.0102 for children under 5 years from dairy households. Most of the estimated health burden was born by children. Although dairy cattle are the source of Cryptosporidium, the model suggests consumption of vegetables is a greater source of risk than consumption of milk. In conclusion, by combining participatory methods with quantitative microbial risk assessment, we were able to rapidly, and with appropriate 'imprecision', investigate health risk to communities from Cryptosporidium and identify the most vulnerable groups and the most risky practices.