Quantitative PCR-Based Diagnosis and Follow-up of Chagas Disease Primary Infection After Solid Organ Transplant: A Multicentre Study.

Chagas disease in solid organ transplant recipients may present as a primary infection (PI). Early detection is crucial for timely treatment. This is the largest observational multicentre study evaluating qPCR for early diagnosis and treatment monitoring of PI in seronegative recipients of organs from seropositive donors. Of 34 patients admitted at 5 health centers, PI was detected by qPCR in 8 (23.5%) within a posttransplant period of 40 days (interquartile range [IQR], 31-50 days). No PI was detected by the Strout test or clinical symptoms/signs. All patients had favorable treatment outcome with negative qPCR 31 days (IQR, 18-35 days) after treatment, with no posttreatment relapse episodes.

Loop-Mediated Isothermal Amplification of Trypanosoma cruzi DNA for Point-of-Care Follow-Up of Anti-Parasitic Treatment of Chagas Disease.

A loop-mediated isothermal amplification assay was evaluated as a surrogate marker of treatment failure in Chagas disease (CD). A convenience series of 18 acute or reactivated CD patients who received anti-parasitic treatment with benznidazole was selected-namely, nine orally infected patients: three people living with HIV and CD reactivation, five chronic CD recipients with reactivation after organ transplantation and one seronegative recipient of a kidney and liver transplant from a CD donor. Fifty-four archival samples (venous blood treated with EDTA or guanidinium hydrochloride-EDTA buffer and cerebrospinal fluid) were extracted using a Spin-column manual kit and tested by T. cruzi Loopamp kit (Tc-LAMP, index test) and standardized real-time PCR (qPCR, comparator test). Of them, 23 samples were also extracted using a novel repurposed 3D printer designed for point-of-care DNA extraction (PrintrLab). The agreement between methods was estimated by Cohen's kappa index and Bland-Altman plot analysis. The T. cruzi Loopamp kit was as sensitive as qPCR for detecting parasite DNA in samples with parasite loads higher than 0.5 parasite equivalents/mL and infected with different discrete typing units. The agreement between qPCR and Tc-LAMP (Spin-column) or Tc-LAMP (PrintrLab) was excellent, with a mean difference of 0.02 [CI = -0.58-0.62] and -0.04 [CI = -0.45-0.37] and a Cohen's kappa coefficient of 0.78 [CI = 0.60-0.96] and 0.90 [CI = 0.71 to 1.00], respectively. These findings encourage prospective field studies to validate the use of LAMP as a surrogate marker of treatment failure in CD.

Hypercalcemia as an Early Finding of Opportunistic Fungal Pneumonia in Renal Transplantation: A Case Series Report.

BACKGROUND: Pneumonia caused by opportunistic fungi is a serious complication in immunocompromised patients. Hypercalcemia has been described in renal transplantation associated with Pneumocystis jirovecii (PJP) or Histoplasma capsulatum (HCP) pneumonia. METHODS: We describe 5 patients who underwent kidney transplant between 2014 and 2019 and developed hypercalcemia before the diagnosis of pulmonary fungal infection: 4 patients with PJP and 1 with HCP. We assessed calcium metabolism and kidney function by total and ionized calcium, phosphorus, intact parathormone (iPTH), 25-OH vitamin D, 1,25(OH)2 vitamin D, and serum creatinine levels. RESULTS: Mean albumin-corrected calcium and ionized calcium were 12.56 mg/dL (range, 10.8-13.8 mg/dL) and 1.57 mmol/L (range, 1.43-1.69 mmol/L). Patients were normocalcemic, at 10.12 mg/dL (range, 9.6-10.5 mg/dL), before diagnosis and resolved hypercalcemia after antifungal treatment, at 8.86 mg/dL (range, 8.0-9.5 mg/dL). All patients had low or normal iPTH values, at 29.1 pg/mL (range, <3-44 pg/mL), with higher PTH levels 3 months before diagnosis and after treatment, at 147.3 pg/mL (range, 28.1-479 pg/mL) and 117.5 pg/mL (range, 18.2-245 pg/mL), respectively. The mean value for 25-OH vitamin D was 30.8 ng/mL (range, 14.6-62.8 ng/mL). This supports a PTH-independent mechanism, and we postulated an extrarenal production of 1,25(OH)2 vitamin D. CONCLUSION: In kidney transplant patients, hypercalcemia independent of PTH and refractory to treatment should alert for the possibility of opportunistic fungal pneumonia.

Spontaneous bacterial peritonitis recurrence in patients with cirrhosis receiving secondary prophylaxis with norfloxacin.

OBJECTIVE: Few studies carried out more than 20 years ago have evaluated spontaneous bacterial peritonitis (SBP) recurrence in patients receiving secondary antibiotic prophylaxis. These studies reported a 1-year recurrence rate of 20-26%. Changes in the bacteriology of SBP over the last few years might have negative effects on secondary prophylaxis. Our primary aim was to estimate the incidence of SBP recurrence in patients with cirrhosis receiving secondary prophylaxis with norfloxacin and to explore the factors associated with SBP recurrence. PATIENTS AND METHODS: This was a retrospective cohort study of patients receiving norfloxacin for the secondary prophylaxis of SBP from 1 March 2003 to 31 March 2016. Follow-up was performed for 365 days after secondary prophylaxis was started. A competing risk analysis approach was used. RESULTS: A total of 115 patients were included. The prevalence of quinolone-resistant and multiresistant bacteria in the first episode of SBP among patients with culture-positive SBP was 70.96% [95% confidence interval (CI): 51.96-85.77%] and 12.90% (95% CI: 3.63-29.83%), respectively. The cumulative incidence of SBP recurrence was 28.53% (95% CI: 20.15-37.45%) after 365 days. Male patients showed an estimated subhazard ratio of SBP recurrence of 2.52 (95% CI: 1.07-5.91, P=0.034). No other risk factors for SBP recurrence were identified. The overall cumulative incidence of death after 365 days was 21.57% (95% CI: 14.14-30.04%), without significant differences among patients with or without SBP recurrence. CONCLUSION: Even though changes in the bacteriology of SBP occurred over time, its recurrence rate in patients receiving norfloxacin remains similar to what was reported in the initial studies.

Pandemic influenza A/H1N1 virus infection in solid organ transplant recipients: a multicenter study.

BACKGROUND: The 2009 novel influenza A/H1N1 virus pandemic did not spare solid organ transplant (SOT) recipients. We aimed to describe the behavior of pandemic influenza infection in a group of SOT recipients in Argentina. METHODS: Data from 10 transplant (Tx) centers were retrospectively collected for SOT that presented with a respiratory illness compatible with pandemic influenza A infection, between May and September 2009. Cases were defined as suspected, probable, or confirmed according to diagnostic method. RESULTS: Seventy-seven cases were included. No significant differences in presenting symptoms, pulmonary infiltrates, and graft involvement were found among 35 suspected, 19 probable, and 23 confirmed cases. The 33 ambulatory cases had significantly more sore throat and headache when compared with 34 cases admitted to medical ward (MW) and 10 admitted to intensive care unit (ICU), 9 of whom required ventilatory support. MW and ICU cases had significantly more dyspnea, hypoxemia, pulmonary infiltrates, and graft dysfunction. Time from onset of symptoms to first visit and to treatment was significantly longer in MW and ICU cases (P=0.008). Coinfections were found in six cases. Most cases received oseltamivir for 5 to 10 days. Six patients (7.8%) died from viral infection at a median of 15 days from admission. No differences in outcome were seen related to the transplanted organ, the immunosuppressive regimen, time from Tx, or confirmation of diagnosis. CONCLUSIONS: Mortality is higher in Tx recipients than in the general population. Poor outcome seems to be related to a delay in the beginning of treatment.

Agreement analysis of variables involved in lipodystrophy syndrome definition in HIV-infected patients.

BACKGROUND: Lipodystrophy studies in HIV-infected patients have usually defined abnormalities in body fat by clinical evaluation and patient questionnaires. Despite the risk for bias with these subjective approaches, agreement analysis among the large number of variables employed was seldom performed. OBJECTIVE: To analyze consistency between the usual approaches for definition of abnormalities in body fat distribution. DESIGN: We evaluated agreement between the clinical and questionnaire findings for abnormalities in body fat in an HIV patient population under antiretroviral treatment followed in our institution, using different criteria for definitions of body fat abnormalities within the same data set. METHODS: Kappa analysis for consistency and receiver-operator characteristic (ROC) curve analysis were performed. RESULTS: Low levels of agreement between clinical and patient perspectives were observed. Only one combination of criteria showed adequate agreement results. The waist/hip ratio showed low levels of agreement with all other variables, and no clear discriminative point was observed by ROC curve analysis. The ratio between the trunk fat content and the leg fat content assessed by dual energy x-ray absorptiometry (DEXA) scan demonstrated better agreement and more clear discriminative values for both male and female patients. CONCLUSION: Agreement analyses may help in the selection of the subjective variable methodology and in the inclusion of consistent and nonredundant objective measurements for diagnosis of abnormalities in body fat.

Toxoplasma gondii pneumonia in liver transplantation: survival after a severe case of reactivation.

Toxoplasmosis is an infrequent infection in solid organ transplantation, except in heart transplantation, where the grafting of a positive organ in a negative recipient transmits the infection in a high percentage of cases, in the absence of prophylaxis. We report a case of pneumonia by Toxoplasma gondii in a woman who received a liver transplant and had pre-transplant positive serology. Diagnosis was made by cytologic examination of bronchoalveolar lavage fluid, where the parasite was observed with hematoxylin-eosin and Giemsa staining. That finding was confirmed by direct immunofluorescence and positive polymerase chain reaction. The patient had a favorable outcome, although she had not initially received first-choice drugs. This was a case of severe illness secondary to reactivation of Toxoplasma infection, diagnosed pre-mortem and with a favorable outcome. Duration of treatment and need for secondary prophylaxis in these patients are discussed in the literature. Although infrequent, toxoplasmosis must be considered among the differential diagnoses of pulmonary infiltrates in solid organ transplantation.