Case Report: Refractory Cryptosporidiosis after CAR T-Cell Therapy for Lymphoma.

Cryptosporidial diarrhea is uncommon in immunocompetent individuals, more often seen in severely immunocompromised patients. Severe refractory cases have been described in patients with HIV/AIDS before the advent of modern antiretroviral therapy due to an inability to mount an adequate cellular immune response. We describe an 85-year-old patient post-chimeric antigen receptor T-cell therapy relapsed lymphoma who developed refractory Cryptosporidium spp. diarrhea in the setting of persistent CD4+ cytopenia. Despite receiving multiple antiparasitic agents, including failure of a prolonged course of nitazoxanide, the patient experienced persistent symptoms for 9 months with repeatedly positivity stool Cryptosporidium spp. direct fluorescent antibody (DFA) test. We highlight this case of refractory Cryptosporidium spp. and the importance of recognizing the pathogen in a non-HIV-infected immunosuppressed host.

Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: Evidence from the Global Enteric Multicenter Study.

Diarrhea is a leading cause of antibiotic consumption among children in low- and middle-income countries. While vaccines may prevent diarrhea infections for which children often receive antibiotics, the contribution of individual enteropathogens to antibiotic use is minimally understood. We used data from the Global Enteric Multicenter Study (GEMS) to estimate pathogen-specific incidence of antibiotic-treated diarrhea among children under five years old residing in six countries of sub-Saharan Africa and South Asia before rotavirus vaccine implementation. GEMS was an age-stratified, individually-matched case-control study. Stool specimens were obtained from children presenting to sentinel health clinics with newly-onset, acute diarrhea (including moderate-to-severe and less-severe diarrhea) as well as matched community controls without diarrhea. We used data from conventional and quantitative molecular diagnostic assays applied to stool specimens to estimate the proportion of antibiotic-treated diarrhea cases attributable to each pathogen. Antibiotics were administered or prescribed to 9,606 of 12,109 moderate-to-severe cases and 1,844 of 3,174 less-severe cases. Across all sites, incidence rates of clinically-attended, antibiotic-treated diarrhea were 12.2 (95% confidence interval: 9.0-17.8), 10.2 (7.4-13.9) and 1.9 (1.3-3.0) episodes per 100 child-years at risk at ages 6 weeks to 11 months, 12-23 months, and 24-59 months, respectively. Based on the recommendation for antibiotic treatment to be reserved for cases with dysentery, we estimated a ratio of 12.6 (8.6-20.8) inappropriately-treated diarrhea cases for each appropriately-treated case. Rotavirus, adenovirus serotypes 40/41, Shigella, sapovirus, Shiga toxin-producing Escherichia coli, and Cryptosporidium were the leading antibiotic-treated diarrhea etiologies. Rotavirus caused 29.2% (24.5-35.2%) of antibiotic-treated cases, including the largest share in both the first and second years of life. Shigella caused 14.9% (11.4-18.9%) of antibiotic-treated cases, and was the leading etiology at ages 24-59 months. Our findings should inform the prioritization of vaccines with the greatest potential to reduce antibiotic exposure among children.

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.

Colorectal cancer and Cryptosporidium spp. infection.

Transient or constant impaired immunity is often associated with neoplastic disease or oncological treatment. Among the most common pathogens found in patients with HIV or patients undergoing chemotherapy are protozoans of the Cryptosporidium genus, which cause diarrhea in humans and animals. The present study determined the frequency of Cryptosporidium spp. infections in patients with colorectal cancer (N = 108; 42 women; 66 men; median age, 65 years), before beginning oncological treatment, compared to a control group (N = 125; 56 women, 69 men; median age, 63 years) without colorectal cancer or a history of oncological disease. We also assessed whether Cryptosporidium spp. infections were associated with age, gender, cancer stage (based on Astler-Coller or TNM classification), histological grade, or cancer location. Patients were treated at the Pomeranian Medical University, in 2009-2014. The presence of Cryptosporidium spp. antigen was determined in stool samples, analyzed with a commercial immunoenzymatic test. Cryptosporidium spp. infections occurred significantly more often (p = 0.015) in patients (13%) compared to controls (4%). The patient group showed no significant relationship between Cryptosporidium spp. infection and sex, age, tumor location, cancer grade, or stage. A multivariate logistic regression analysis adjusted for age and sex that included all subjects (patient + control groups, n = 233) showed that the odds of a Cryptosporidium spp. infection were more than three-fold higher in patients than in controls, and more than six-fold higher among men than among women. CONCLUSIONS: 1) Cryptosporidium spp. infections occurred significantly more frequently in patients with colorectal cancer (before oncological treatment) compared to controls, independent of age and sex. 2) Cryptosporidium spp. infections were not associated with the colorectal cancer stage, grade, or location or with patient age. 3) Male gender was significantly related to the frequency of Cryptosporidium spp. infections, independent of age and the presence of colorectal cancer.

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.

Prevalence of Cryptosporidium species and subtypes in paediatric oncology and non-oncology patients with diarrhoea in Jordan.

Cryptosporidiosis is a protozoan parasitic disease which affects human and animals worldwide. In adult immunocompetent individuals, cryptosporidiosis usually results in acute and self-limited diarrhoea; however, it can cause life threatening diarrhoea in children and immunocompromised individuals. In the present study, we compared the prevalence of Cryptosporidium species and gp60 subtypes amongst paediatric oncology patients with diarrhoea (n=160) from King Hussein Medical Centre for Cancer in Jordan, and non-oncology paediatric patients with diarrhoea (n=137) from Al-Mafraq paediatric hospital. Microscopy results using modified acid fast staining identified a significantly (p≤0.05) higher prevalence of Cryptosporidium in paediatric oncology patients with diarrhoea (14.4% - 23/160), compared to non-oncology paediatric patients with diarrhoea only (5.1% - 7/137). With the exception of one sample, all microscopy-positive samples (n=29) and an additional 3/30 microscopy-negative controls were typed to species and subtype level at the 18S and gp60 loci, respectively. All Cryptosporidium positives were typed as C. parvum. Of the 22 typed Cryptosporidium positives from the paediatric oncology patients, 21 were subtyped as IIaA17G2R1 and one as IIaA16G2R1 C. parvum subtypes. The 7 typed positives from the paediatric patients from Al-Mafraq hospital were subtyped as IIaA17G2R1 (n=5) and IIaA16G2R1 (n=2). The 3 additional positives from the 30 microscopy negative control samples were subtyped as IIaA17G2R1. The high prevalence of the IIaA17G2R1 subtype, particularly amongst oncology patients, suggests that an outbreak of cryptosporidiosis may have been occurring in oncology patients during the collection period (April to December, 2016). New therapies for cryptosporidiosis in immunocompromised patients are urgently required.

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.

Cryptosporidium infections in birds - a review / Infecção por Cryptosporidium em aves - uma revisão

Cryptosporidiosis is one of the main protozoan infections in birds. It manifests as either a respiratory or a digestive illness, and it affects a very large number of avian species across several continents. The aim of this review is to report on the main results of studies on cryptosporidiosis among birds and the importance of these results to veterinary medicine and public health.

A criptosporidiose constitui-se em uma das principais infecções por protozoários em aves, manifestando-se como enfermidade respiratória ou digestiva, em dezenas de espécies aviárias, em vários continentes. O objetivo desse trabalho foi relatar, por meio de revisão de literatura, os principais resultados de estudos sobre criptosporidiose em aves e sua importância para a medicina veterinária e saúde pública.

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.

Prevalencia y factores de riesgo de Cryptosporidium spp. y Giardia spp. en terneros de ganado lechero de la zona noroccidental de la Sabana de Bogotá / Cryptosporidium spp. and Giardia spp. prevalence and risk factors in dairy calves of the north-western zone of the Bogota Savanna

Objetivo Estimar la prevalencia de Cryptosporidium spp. y Giardia spp. en terneros de 0 a 2 meses de ganado lechero de la zona noroccidental de la Sabana de Bogotá. Se estimaron los factores de riesgo de la producción lechera que puedan incurrir en la infección de personas y animales. Métodos Estudio de corte transversal, mediante la toma de materia fecal de terneros. Se determinó la prevalencia de punto para Giardia spp. y Cryptosporidium spp. a través los resultados de los coprológicos (Ritchie para Giardia spp. y Ziehl-Neelsen modificada para Cryptosporidium spp.). Se calcularon Odds Ratio para establecer los factores de riesgo asociados entre estos dos géneros de protozoarios y el manejo de las Buenas Prácticas Ganaderas. Resultados Se evaluaron 33 fincas dedicadas a la producción lechera, donde se muestrearon 308 terneros. La prevalencia para Giardia spp. fue de 37,3 %, 115 animales positivos y para Cryptosporidium spp. fue de 4,9 % 15, animales positivos. Conclusión Existe un foco de Giardia spp. y Cryptosporidium spp. en el noroccidente de la Sabana de Bogotá, del cual no se tenía conocimiento previo. La prevalencia de Giardia spp. para la región estudiada, está en el límite alto del rango reportado para Sudamérica. En el caso de Cryptosporidium spp. la situación es distinta, la prevalencia se encuentra en el limite bajo del rango reportado para Sudamérica. Los factores de riesgo asociados a Giardia spp. y Cryptosporidium spp. en las explotaciones lecheras del noroccidente de la Sabana de Bogotá, dependen de Buenas Prácticas Ganaderas.

Objective The present study was aimed to establishing Cryptosporidium spp. and Giardia spp. prevalence in 0 to 2 months old dairy calves of the north-western zone of the Bogota Savanna. In addition, associated factors related to a failure in Good Practices of Livestock could incur in human and animal infection. Methods This was a cross-sectional study; calves' fecal samples were used. Farms' Good Practices of Livestock were observed by means of an observation blank. Giardia spp. and Cryptosporidium spp. prevalence was determinate by means of laboratory results (Ritchie for Giardia spp. and modified Ziehl-Neelsen for Cryptosporidium spp.). Odds Ratios (OR) were calculated in association between this two genera of protozoa and Good Practices of Livestock. Results Thirty three dairy farms were evaluated, where fecal samples of 308 calves were taken. Giardia spp. prevalence was 37.7 %, 115 infected animals; Cryptosporidium spp. prevalence was 4.9 %, 15 infected animals. Conclusion There is an important Giardia spp. and Cryptosporidium foci in the north-western zone of the Bogota Savanna, without a previous knowledge. Giardia spp. prevalence for this zone is in the highest rank reported for South-America and Cryptosporidium spp. prevalence is in en the lowest one. Associated risk factors of Giardia spp. and Cryptosporidium spp. in dairy farms of the north-western zone of the Bogota Savanna depend of a Good Practices of Livestock performance.

[Epidemiological aspects of gastrointestinal infections]. / Epidemiologische Aspekte gastrointestinaler Infektionen.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate seasonal patterns and age-associated trends of the main bacterial, viral, and parasitic enteric pathogens in Southwest Germany. PATIENTS AND METHODS: From January 2002 through December 2008 a total of 99,057 patients were tested for Norovirus, Rotavirus, bacterial pathogens, Cryptosporidium parvum (C. parvum), and Giardia lamblia (G. lamblia). RESULTS: All these pathogens were detected throughout the whole year. But there were distinctive seasonal patterns of activity of the following pathogens being detected: norovirus was detected mainly from September through April. The highest rotovirus activity was observed from December through June. But bacterial pathogens und C. parvum were found mainly from June to November. The percentage of positive results during the months with the highest activity was 10 - 49% for norovirus, 25% - 41% for rotavirus, 14 - 18% for bacterial infection and 3 - 4 % for C. parvum. G. lamblia and adenovirus were found throughout the year in 7 - 15% and 3 - 10% of samples, respectively. Moreover, the detection rate of different pathogens depended on patient age. In infants younger than one year, rotavirus, norovirus and adenovirus were most frequently isolated pathogenes. Stool samples from kindergarden- and school-age children were positive largely for bacterial pathogens such as Salmonella and Campylobacter particularly in late summer or early autum. In patients older than 60 years, norovirus, rotavirus, and toxin producing Clostridium difficile strains were the most common pathogens. CONCLUSIONS: In view of the age and season related frequency of detection of enteric pathogens, a step-by-step diagnosis of gastrointestinal tract infections is recommended. Considering that most pathogens are detected sporadically over the whole year, the analysis of negative samples should be appropriately expanded. The knowledge of seasonal occurrence can also be applied to improve the application of hygienic measures.

Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study.

Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

Criptosporidiosis broncopulmonar en pacientes infectados por el virus de la inmunodeficiencia humana / Pulmonary cryptosporidiosis in AIDS patients

La criptosporidiosis pulmonar es una rara complicación de la enfermedad intestinal causada por este agente en pacientes con SIDA. En este trabajo se describen las características epidemiológicas, clínicas, radiológicas, microbiológicas e inmunológicas de 5 pacientes con SIDA y criptosporidiosis pulmonar. El diagnóstico de la localización pulmonar se basó en el hallazgo de ooquistes de Cryptosporidium spp. en muestras de esputo o lavado broncoalveolar utilizando la coloración de Kinyoun. Los laboratorios de microbiología deben estar alerta ante la posibilidad de identificar ooquistes de Cryptosporidium spp. en secreciones broncopulmonares de pacientes con enfermedad VIH/SIDA avanzada.

Pulmonary cryptosporidiosis is a rare complication of intestinal cryptosporidiosis in AIDS patients. We report the epidemiological, clinical, radiological, microbiological and immunological findings in 5 AIDS patients with pulmonary cryptosporidiosis. Diagnosis was based on the detection of acid-fast oocysts in sputum or aspirated bronchial material using the Kinyoun technique. Microbiology laboratories should be alert to the possibility of Cryptosporidium spp oocysts presence in respiratory specimens from patients with advanced HIV/AIDS disease and pulmonary involvement.

Cryptosporidium hominis infection of the human respiratory tract.

Cryptosporidium oocysts, observed in a natural sputum sample of a patient with HIV, were further studied by using DNA markers to determine the species of the parasite. C. hominis was identified as the species infecting the patient's respiratory tract, a finding that strengthens evidence regarding this pathogen's role in human disease.