Cryptosporidiosis In AIDS Patients Research Articles

1588 A Case of Suspected Adalimumab-Induced Apoptotic Colonopathy

INTRODUCTION: Adalimumab is an anti-TNFa monoclonal antibody used for the treatment of multiple autoimmune diseases including IBD. Although it has shown a great benefit minimizing the burden of symptoms, it carries multiple side effects such as headache, nausea, vomiting, abdominal pain, rash, gastrointestinal hemorrhage and even diverticulitis. We present a rare side effect associated to this immune modulator. CASE DESCRIPTION/METHODS: A 40-year-old female with a PMH of Crohn's disease presented for a routine visit to the GI clinic. The patient had been undergoing treatment with adalimumab for past eight months, with non-adherence to treatment. She reported one loose bowel movement per day but denied any tenesmus, urgency, abdominal pain, bleeding or extra-intestinal manifestations. A follow-up colonoscopy showed a stricture in the ileo-cecal valve and a 0.5 centimeter aphthous ulcer in the ascending colon (Figure 1). Biopsies of the ileocecal valve and rectal area showed active chronic inflammation, while the ascending, transverse and descending colon showed inactive chronic colitis. Furthermore, the biopsy of the ileocecal and ascending colon revealed drug-induced apoptosis (Figure 2). She was switched to infliximab due to mentioned histopathological findings of apoptotic colopathy. She was also referred to colorectal surgery for evaluation of stricture and fistula formation. DISCUSSION: Apoptotic enteropathy describes a type of injury to the gastrointestinal mucosa, characterized by epithelial cell apoptosis. This characteristic histological feature can be caused by different etiologies like GI Graft versus host disease (GVHD), infections (CMV, adenovirus and cryptosporidiosis in AIDS patients) and drug induced injury. Medications linked to these histopathological changes are mainly immuno modulators: MMF, CTLA-4 inhibitors (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab and avelumab), idelalisib, tumor necrosis alpha inhibitors (etanercept, infliximab) and anti-metabolites (methotrexate, capecitabine). Furthermore, there is only one case report elucidating the relation between adalimumab with apoptotic colopathy, which showed affectation of the right colon, being the same location of our patient's injury. We present this case to make physicians aware of this entity, since is an important feature to monitor in patients needing biologics. Furthermore, a repeated endoscopic evaluation should be done in order to assess resolution of pathology.

Approximate Bayesian evaluations of measurement uncertainty

The Guide to the Expression of Uncertainty in Measurement (GUM) includes formulas that produce an estimate of a scalar output quantity that is a function of several input quantities, and an approximate evaluation of the associated standard uncertainty.This contribution presents approximate, Bayesian counterparts of those formulas for the case where the output quantity is a parameter of the joint probability distribution of the input quantities, also taking into account any information about the value of the output quantity available prior to measurement expressed in the form of a probability distribution on the set of possible values for the measurand.The approximate Bayesian estimates and uncertainty evaluations that we present have a long history and illustrious pedigree, and provide sufficiently accurate approximations in many applications, yet are very easy to implement in practice. Differently from exact Bayesian estimates, which involve either (analytical or numerical) integrations, or Markov Chain Monte Carlo sampling, the approximations that we describe involve only numerical optimization and simple algebra. Therefore, they make Bayesian methods widely accessible to metrologists.We illustrate the application of the proposed techniques in several instances of measurement: isotopic ratio of silver in a commercial silver nitrate; odds of cryptosporidiosis in AIDS patients; height of a manometer column; mass fraction of chromium in a reference material; and potential-difference in a Zener voltage standard.

An advanced uracil DNA glycosylase-supplemented loop-mediated isothermal amplification (UDG-LAMP) technique used in the sensitive and specific detection of Cryptosporidium parvum, Cryptosporidium hominis, and Cryptosporidium meleagridis in AIDS patients

The rapid and accurate detection of Cryptosporidium spp. is critically important for the prevention and timely treatment of cryptosporidiosis in AIDS patients (APs). This study was conducted to examine a UDG-LAMP technique for the first time to diagnose cryptosporidiosis in APs. After collecting demographic and clinical data, three stool samples were collected from the participants (120 volunteering APs). The microscopic examination of stained smears using the acid-fast method and the UDG-LAMP assay were performed for each sample. 10% of APs were infected with Cryptosporidium spp. The number of detected cryptosporidiosis cases using the acid-fast staining and UDG-LAMP methods were significantly different (P < 0.001). Diarrhea and weight loss were found to be significantly associated with cryptosporidiosis in patients (P < 0.05). The pretreatment of LAMP reagents with UDG successfully eliminated the likelihood of product re-amplification remaining from previous reactions. The UDG-LAMP technique could detect cryptosporidiosis in APs with high sensitivity and rapidity without carryover contamination.

Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cryptosporidium parvum.

With the spread of the human immunodeficiency virus in the early 1980s, cryptosporidiosis was regarded as an AIDS-defining disease. As an opportunistic pathogen, the intestinal parasite Cryptosporidium parvum became an important cause of chronic diarrhoea, leading to high morbidity and mortality in immunocompromised patients. To date, no effective chemotherapy is available. With the introduction of protease inhibitors (PIs) in highly active antiretroviral therapy (HAART), the incidence of cryptosporidiosis in AIDS patients has declined substantially in western countries. We have therefore tested the effect of five PIs used in HAART on the excystation, invasion and development of the parasite in a cell culture system. The human ileocaecal adenocarcinoma cell line HCT-8 served as a host cell. None of the substances had an effect on the excystation rate, and only nelfinavir moderately, but statistically significantly, inhibited the host cell invasion over a period of 2 h. There were more pronounced inhibitory effects when PIs were present over the total time of intracellular development (48 h). Indinavir, nelfinavir and ritonavir inhibited parasite development significantly. The inhibitory effect was increased when the aminoglycoside paromomycin was combined with the PIs indinavir, ritonavir, and to a lesser extent saquinavir, compared to the PIs alone.

Analysis of the spatial distribution of cryptosporidiosis in AIDS patients in San Francisco using density equalizing map projections (DEMP)

Environmental transmission of cryptosporidiosis has occurred repeatedly in defined spatial areas during outbreaks of disease attributed, for example, to drinking water contamination. Little work has been done to investigate the possibility of cryptosporidiosis infection in defined spatial areas in non-outbreak (i.e., endemic) settings. This study applies a novel approach to the investigation of the spatial distribution of cryptosporidiosis in AIDS patients in San Francisco. Density equalizing map projection (DEMP) maps were created for nine race/ethnicity-age groups of AIDS patients based on census tract of residence. Additionally, census tracts with a “high density” of cryptosporidiosis cases were identified by applying smoothing techniques to the DEMP maps, and included as a covariate in multivariate Poisson regression analyses of other known risk factors for cryptosporidiosis. These analyses suggest: (1) cases of cryptosporidiosis among Black and Hispanic AIDS patients, but not among Whites, show a statistically significant non-random spatial distribution (p<0.05) even after adjustment for the underlying spatial distribution of AIDS patients for these demographic groups, and (2) the risk of residence in these high density census tracts, adjusted for other known risk factors, was not statistically significant (relative risk=1.27, 95% confidence interval 0.15, 10.53). These results do not support an independent effect of spatial distribution on the transmission of cryptosporidiosis among AIDS patients.

Epidemiology of cryptosporidiosis among European AIDS patients.

To study epidemiology and possible risk factors associated with the development of cryptosporidiosis among European patients with AIDS. An inception cohort of 6548 patients with AIDS, consecutively diagnosed from 1979 to 1989, from 52 centres in 17 European countries was studied. Data on all AIDS defining events were collected retrospectively from patients' clinical records. Kaplan-Meier estimates, log rank tests and Cox proportional hazard models were used to examine for possible risk factors associated with cryptosporidiosis. Cryptosporidiosis was diagnosed in 432 (6.6%) patients, 216 at time of the AIDS diagnosis and 216 during follow-up. The probability of being diagnosed with cryptosporidiosis at AIDS diagnosis was significantly lower for intravenous drug users (1.3%) than for homosexual men (4.1%) and for patients belonging to other transmission categories (4.0%) (p < 0.001). The probability was also higher for patients from Central Europe compared with patients from South Europe (4.1% versus 2.5%, p = 0.005). The rate of developing cryptosporidiosis after the diagnosis of AIDS was 3 per 100 patient years of follow-up. The rate was significantly lower for intravenous drug users than for homosexual men (relative risk 0.34, 95% confidence limits 0.22-0.54) and for women compared with men (RR 0.43 (0.21-0.87)). The risk was higher in North Europe than in South and Central Europe. In a multivariate analysis only transmission category remained a significant predictor for the development of cryptosporidiosis. The development of cryptosporidiosis in AIDS patients may be associated with sexual risk behaviour.

Microbiological findings about pulmonary cryptosporidiosis in two AIDS patients

There is no known treatment for pulmonary cryptosporidiosis, a rare complication of intestinal cryptosporidiosis in AIDS patients. We report two cases of cryptosporidiosis which were unusual because (i) extracellular invasive forms of the parasite were found in the bronchoalveolar lavage and (ii) the outcome was favorable in one patient after treatment with azithromycin.

Intestinal and extraintestinal cryptosporidiosis in AIDS patients.

In a prospective study in AIDS patients with chronic diarrhea, the overall prevalence of intestinal cryptosporidiosis was 15.6% (43/275). The prevalence was higher in homosexual patients (33.3%) than in intravenous drug abusers (10.6%) (p < 0.001). Extraintestinal infection was present in 30% (13/43) of the patients with known intestinal cryptosporidiosis. Eight of the 13 (61.5%) patients with extraintestinal cryptosporidiosis had Cryptosporidium in the bile and 7 of 13 (16.28%) had it in the sputum. Of the seven patients with Cryptosporidium in the sputum, four had respiratory symptoms and an abnormal chest radiograph, although another pulmonary pathogen was isolated simultaneously. Two other patients from whom Cryptosporidium was the sole respiratory pathogen isolated had no respiratory symptoms and normal chest radiographs. The seventh patient had pulmonary symptoms, interstitial infiltrate on chest radiograph and excessive activity on a pulmonary Gallium scan; Cryptosporidium was the only organism detected in induced sputum and bronchoalveolar lavage specimens. The mean CD4+ lymphocyte count in patients with extraintestinal cryptosporidiosis was 55 cells/mm3.

Treatment of Cryptosporidial Diarrhea in an AIDS Patient with Paromomycin

To report a case of diarrhea caused by Cryptosporidium in an AIDS patients which was successfully treated with paromomycin. An AIDS patient with a 12-month history of cryptosporidial diarrhea unresponsive to other treatment measures was treated with paromomycin 500 mg q6h for 14 days. Before initiating therapy, the patient was experiencing, on average, 20 bowel movements per day and had lost more than 25 kg. After therapy was initiated, the number of bowel movements dropped to 1-2 per day and the patient began to gain weight. The diarrhea recurred when therapy was discontinued. After retreatment for 14 days with paromomycin 500 mg q6h, the diarrhea stopped. The patient has not had a recurrence of Cryptosporidium diarrhea, stool cultures remain negative for Cryptosporidium oocysts, and the patient has regained most of the weight. Literature concerning the use of paromomycin for the treatment of cryptosporidiosis is discussed. A treatment algorithm for the management of cryptosporidiosis in AIDS patients is presented. We believe that we have presented a clear example of a case in which paromomycin was effective in treating and eradicating intestinal cryptosporidiosis in an AIDS patient. Paromomycin is the most effective agent available to date for the treatment of this devastating complication of AIDS.

Multiple drug regimen for severe diarrhea associated with Cryptosporidium in aids patients

Cryptosporidium is one of the most common identified causes of chronic diarrhea and malabsorption in AIDS patients. The severity of human cryptosporidiosis in AIDS patients may be correlated with the degree of immune dysfunction that they present. No effective treatment however exists against this disease. An alternative association therapy is therefore suggested to control severe diarrhea in AIDS patients with cryptosporidiosis. A patient with Cryptosporidium-induced diarrhea was first treated with spiramycin without success. Co-trimoxazole and doxycycline were then introduced for prophylaxis of Pneumocystis carinii pneumonia while the subjects chlamydial urethritis was also treated. This regimen brought about a complete recovery of symptoms. Based upon these results the authors went on to treat 5 consecutive patients with Cryptosporidium-induced diarrhea with a combination of 50 mg/kg/day of spiramycin 4 mg/kg/day of doxycycline and co-trimoxazole (25/5 mg/kg/day TMP-SMX). All 5 had a history of 30-45 days of diarrhea with 10-15 episodes daily and weight loss of more than 10%. Further only Cryptosporidia had been identified in their stool prior to treatment. After completing treatment over a period of approximately 1 week all subjects presented with stool samples negative for Cryptosporidium and remained asymptomatic after 3 months of follow-up. The medication was well-tolerated and no significant side-effects were observed. this therapy may therefore be useful in treating cryptosporidiosis in AIDS patients but it requires further evaluation.

Nosocomial outbreak of cryptosporidiosis in AIDS patients.

To describe a nosocomial outbreak of cryptosporidiosis during four months after June 1989. A department of infectious diseases in Copenhagen, seeing about half the patients with AIDS in Denmark. 73 HIV antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak (20 June-14 August), of whom 18 (17 with AIDS, one with AIDS related complex), developed cryptosporidiosis. Two further HIV negative subjects (one departmental secretary, one visiting relative) developed cryptosporidiosis. Cryptosporidia in stool samples, clinical symptoms, CD4 cell count, HIV antigen concentration, chemotherapeutic treatment. The source of the outbreak was identified as ice from an ice machine in the ward, contaminated by an incontinent, psychotic patient with cryptosporidiosis picking out ice for cold drinks. The mean incubation time was at least 13 days-that is, twice that in HIV-negative patients. Of the 18 patients with AIDS who developed cryptosporidiosis, five recovered, two were symptomless carriers, three died of unrelated causes, and eight died after prolonged diarrhoea. Among the 57 exposed HIV antibody positive inpatients (excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere), significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not (91%, 10/11 v 48%, 21/44, p less than 0.05). The clinical and epidemiological findings indicate that infection was the consequence of very small inocula. Increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with AIDS.

No treatment for cryptosporidiosis in AIDS patients

No treatment for cryptosporidiosis in AIDS patients