The latest medical research on Infectious Disease
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Association between cytomegalovirus infection and allograft rejection in a large contemporary cohort of heart transplant recipients.Transplant Infectious Disease
Cytomegalovirus (CMV) infection remains a common complication after heart transplantation (HTx). The association between CMV infection and allograft rejection is debated in the era of efficient prophylactic antiviral therapies.
This single-center cohort study utilized a highly phenotyped database of HTx recipients (2012-2016). The primary endpoint was the analysis of the association between CMV infection (CMV load ≥500 IU/mL whole blood) and the risk of allograft rejection (cellular rejection ≥1R1B, antibody-mediated rejection ≥pAMR1). Secondary endpoints included the analysis of a higher CMV load threshold (≥10,000 IU/mL) and different risk periods after PCR positivity. A mixed effect logistic regression model with a random intercept was applied. Results were adjusted for important risk factors of rejection.
Overall, 384 patients were included and 6,388 CMV loads and 3,494 endomyocardial biopsies were analyzed. CMV infections ≥500 IU/mL were diagnosed on 1,223 (19.2%) blood samples from 284 (72.1%) patients and allograft rejections on 246 biopsies (7%) from 149 patients (38.8%). We did find not any association between CMV infection ≥500 IU/mL and rejection (univariable: OR 0.94, 95% CI [0.61, 1.45], p = 0.78, multivariable: OR 0.86, 95% CI [0.55, 1.33], p = 0.85). These results were consistent when analyzing a higher CMV load threshold and different periods of risk, reinforced by internal validation procedures and a posteriori calculation of the power (primary endpoint: power = 0.82, 95% CI [0.79-0.84]) and reproducible across different clinical scenarios.
CMV infection was not associated with an increased risk of rejection in a contemporary cohort of HTx recipients.
Usefulness of PCR for Trypanosoma cruzi DNA in blood and endomyocardial biopsies for detection of Chagas disease reactivation after heart transplantation: a comparative study.Transplant Infectious Disease
Chagas disease reactivation (CDR) after heart transplantation is characterized by relapse of the infectious disease with proliferation and dissemination of Trypanosoma cruzi parasites. Serial blood PCR testing is consensually recommended for CDR monitoring, but there is uncertainty about the incremental value in performing the molecular tests in endomyocardial biopsies (EMB).
We compared qualitative and quantitative results of PCR for T. cruzi DNA in 62 pairs of blood and EMB collected with a maximum time interval of 7 days, from 34 heart-transplanted, chagasic patients.
Blood PCR resulted positive in 39/62 (62.9%) samples, with PL ranging from 0.14 to 1,610.73 (median: 3.31). PCR resulted positive in 8/60 (13.3%) EMB, with PL ranging from 2.82 to 1,670.55 (median: 65.63). All blood samples which tested negative presented a paired EMB which also tested negative. However, 31/39 (79.5%) blood samples which tested positive presented a paired EMB which tested negative. There was poor agreement between blood and EMB PCR (kappa=0.153). CDR affecting the myocardium (myo-CDR) was diagnosed in three occasions. PCR resulted positive in both blood and EMB at the time of myo-CDR, with PL ranging from 0.61 to 1,610.73 in blood and 13.8 to 1,670.55 in EMB.
Negative PCR for T. cruzi in blood rules out myo-CDR, with no value of testing EMB. Positive PCR in blood with high PL is diagnostic for myo-CDR. If PCR in blood results positive with low PL, testing EMB is useful: negative PCR turns unlikely, and positive PCR reinforces greatly the possibility of myo-CDR.
Evaluation of targeted versus universal prophylaxis for the prevention of invasive fungal infections following lung transplantation.Transplant Infectious Disease
Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI.
Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18 months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts.
Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51-12.38), P = .0064.
Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.
Impact and outcomes of primary cytomegalovirus disease in seronegative abdominal solid organ transplant recipients of cytomegalovirus unexposed donors (d-/r-).Transplant Infectious Disease
Primary cytomegalovirus (CMV) disease in high risk (D+/R-) abdominal solid organ transplant recipients (aSOTRs) is well described, however little is known of primary CMV disease in low risk (D-/R-) patients.
Observational study of adult aSOTRs between 1/1/2009-9/1/2019 screened based on serostatus at transplant; D-/R- and D+/R- patients were included.
compare infectious and transplant related outcomes of primary CMV disease in the first 90 days (early CMV) between D-/R- and D+/R-.
Of 782 D-/R- aSOTRs in the study period, 13 developed CMV at any time after transplant to last follow-up. Of 671 D+/R- patients, 186 developed CMV. Early CMV disease was significantly more common in the D-/R- group (54% vs 15.6%, p=0.0005) despite populations being similar demographically, including allograft subtype. D-/R- patients with early CMV disease had median viral load >100,000 IU/mL and 42.9% had end-organ manifestations; 71.4% required hospital admission. Immunosuppressive therapy was adjusted in 100% of patients, there was an approximately 14.3% rate of antiviral resistance and 28.6% had concomitant opportunistic infection. These findings were similar to D+/R- patients. There was no difference in risk of rejection or all-cause mortality associated with early CMV disease, however graft loss was significantly higher in D-/R- CONCLUSION: D-/R- aSOTRs infrequently develop CMV, however when it occurs, they present with disease manifestations similar to and graft outcomes inferior to D+/R- with CMV. Additionally, the majority of CMV disease in D-/R- occurs in the first 90 days after transplant, suggesting possible donor subclinical infection or transfusion source. The complicated course in D-/R- is likely due to low clinical suspicion. Awareness of disease severity and aggressive upfront management may promote positive outcomes.
Targeted caspofungin prophylaxis for invasive aspergillosis in high-risk liver transplant recipients, a single center experience.Transplant Infectious Disease
Invasive aspergillosis (IA) is a rare but highly lethal complication after orthotopic liver transplantation (OLT). Targeted antifungal prophylaxis has been proposed as a strategy to prevent IA among orthotopic liver transplant recipient (OLTr), but limited data is available to support its efficacy.
We conducted a single center, retrospective, before and after cohort study, comparing IA incidences among OLTr who did not receive antifungal prophylaxis after transplantation (cohort 1) to OLTr who received targeted antifungal prophylaxis after liver transplantation (cohort 2). Patients in cohort 2 received caspofungin prophylaxis if they presented one of the following risk factors: retransplantation, acute liver failure, dialysis or Aspergillus colonization prior to transplantation. The primary outcome was IA at 90 days after transplantation.
A total of 391 OLTr were included in the study; 181 patients in the cohort 1 (no prophylaxis) and 210 patients in the cohort 2 (targeted prophylaxis). Among patients in cohort 2, 19% (40/ 210) were considered at high risk for IA and 85% (34/40) of those received caspofungin prophylaxis. The incidence of IA at 90 days was 3.3% (6/ 181) and 0.5% (1/ 210), in cohort 1 and 2 respectively (OR 0.14; 95%CI 0.01-0.83; P= 0.03). Ninety-day mortality was similar among the two cohorts (3.9% (7/181) and 2.4% (5/210) in cohort 1 and 2, respectively (OR 0.61; 95% 0.18-1.93; P=0.40)). The 90-day mortality among the OLTs with IA was 71% (5/7).
Targeted caspofungin prophylaxis was associated with lower rate of IA.
Disseminated Legionella micdadei Infection in a Liver Transplant Patient Presenting as Pulmonary Nodules and a Laryngeal Lesion.Transplant Infectious Disease
We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. T...
Donor derived herpes simplex virus hepatitis in a kidney transplant recipient and review of the literature.Transplant Infectious Disease
Donor derived (DD) herpes simplex virus (HSV) hepatitis in solid organ transplant (SOT) recipients is extremely uncommon but carries a high mortali...
Malaria and encephalopathy in a heart transplant recipient: a case report in the context of multiorgan donation.Transplant Infectious Disease
Malaria is an endemic infection in tropical circles. It can be transmitted from mosquitoes bite, but exceptional cases have been attributed to multiorgan transplantation.
This is a 34 years-old woman who received a heart transplant for final stage dilated cardiomyopathy. Over the hospitalization, she developed fever, cephalalgia, and tonic-clonic seizures with MRI findings compatible with posterior reversible encephalopathy. A thick blood smear revealed hemoparasitic forms of Plasmodium vivax. Afterward, malaria was also diagnosed in recipients of one kidney and liver of the same organ-donor. First-line treatment with artesunate was prescribed for three days and chloroquine with primaquine thereafter for fourteen days. The patient was discharged and returned to the emergency department five days later, complaining of gastrointestinal symptoms and develop multiorgan failure that led to death.
We report a case of malaria transmission through heart transplantation. Despite adequate and supervised treatment, it can be related to a fatal outcome. Malaria screening in organ donors should be considered in regions where endemicity can lead to rare cases of transmission by transplantation.
Using longitudinal genetic-network study to understand HIV treatment-as-prevention: a population-based observational study.AIDS
The World Health Organization (WHO) has recommended that antiretroviral therapy be provided to all HIV patients to reduce future HIV transmission rates. However, few studies have examined this public health strategy at the population level in a real-world setting.
In this longitudinal genetic-network study in Guangxi, China, the baseline and follow-up data were collected from HIV patients in 2014 and newly diagnosed HIV patients from 2015 to 2018, respectively. The prevention efficacy (PE) was used to estimate the effect of treatment-as-prevention in reducing HIV secondary transmission.
Among 804 newly diagnosed HIV patients during 2015-2018, 399 (49.6%) of them genetically linked to HIV patients at baseline during 2014-2017. The overall proportion of genetic linkage between newly diagnosed HIV patients during 2015-2018 with untreated and treated HIV patients at baseline during 2014-2017 was 6.2% and 2.9%, respectively. The PE in HIV transmission for treated HIV patients was 53.6% (95% CI: 42.1%-65.1%). Subgroup analyses indicated an 80.3% (95% CI: 74.8%-85.8%) reduction in HIV transmission among HIV patients who were treated for 4 years or more and had viral loads <50 copies/ml. There was no significant reduction in HIV transmission among treated HIV patients who dropped out or who had missing viral load measures.
Our study results support the feasibility of treating all HIV patients for future reductions in HIV transmission at the population level in real-world settings. Comprehensive intervention prevention programs are urgently needed.
Incidence of dyslipidemia in people with HIV who are treated with integrase inhibitors versus other antiretroviral agents.AIDS
To compare the incidence of dyslipidemia in people with HIV (PLWH) receiving integrase inhibitors (INSTI) versus boosted protease inhibitors (PI/b) and non-nucleoside reverse transcriptase inhibitors (NNRTI) within RESPOND consortium of prospective cohorts.
Participants were eligible if they were ≥18 years, without dyslipidemia and initiated or switched to a three-drug ART-regimen consisting of either INSTI, NNRTI or PI/b for the first time, between 01/01/2012 and 31/12/2018. Dyslipidemia was defined as random total cholesterol >240 mg/dL, high-density lipoprotein < 35 mg/dL, triglyceride >200 mg/dL, or initiation of lipid-lowering therapy. Poisson regression was used to determine the adjusted incidence rate ratios (aIRR). Follow-up was censored after three years or upon ART-regimen discontinuation or last lipid measurement or 31/12/2019, whichever occurred first.
Overall, 4577 PLWH were eligible (INSTI = 66.9%, PI/b = 12.5%, and NNRT = 20.6%), 1938 (42.3%) of whom were ART-naive. During 1.7 (interquartile range, 0.6-3.0) median years of follow-up, 1460 participants developed dyslipidemia (incidence rate: 191.6 per 1000 person-years, 95% confidence interval [CI] 182.0-201.7). Participants taking INSTI had a lower incidence of dyslipidemia compared to those on PI/b (aIRR 0.71; CI 0.59-0.85), but higher rate compared to those on NNRTI (1.35; CI 1.15-1.58). Compared to dolutegravir, the incidence of dyslipidemia was higher with elvitegravir/cobicistat (1.20; CI 1.00-1.43) and raltegravir (1.24; CI 1.02-1.51), but lower with rilpivirine (0.77; CI 0.63-0.94).
In this large consortium of heterogeneous cohorts, dyslipidemia was less common with INSTI than with PI/b. Compared to dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir, but less common with rilpivirine.
HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART.HIV Medicine
Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed-death-1 (PD-1) has been linked to the HIV reservoir and T-cell immune dysfunction. We thus evaluated PD-1 expression and cell-associated HIV DNA in memory CD4 T-cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV-positive patients to identify associations between PD-1 and HIV reservoir in other sites.
Using mononuclear cells from PB, TI and RE of untreated HIV-positive (N = 6), treated (n = 18) HIV-positive and uninfected individuals (n = 16), we identified and sorted distinct memory CD4 T-cell subsets by flow cytometry, quantified their cell-associated HIV DNA using quantitative PCR and assessed PD-1 expression levels using geometric mean fluorescence intensity. Combined HIV-1 RNA in situ hybridization and immunohistochemistry was performed on ileal biopsy sections.
Combined antiretroviral therapy (cART)-treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD-1 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment-naïve patients HIV DNA levels in memory CD4 T-cell subsets were high in PB and TI.
Elevated PD-1 expression on memory CD4 T-cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T-cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis.
Differences in hypertension and prehypertension among people living with and without HIV in China: role of HIV infection and antiretroviral therapy.HIV Medicine
Hypertension is a growing health concern in people living with HIV (PLWH). However, association between HIV infection and hypertension is equivocal.
In all, 1472 PLWH and 2944 HIV-negative individuals frequency-matched by age and sex were derived from the baseline survey of Comparative HIV and Aging Research in Taizhou (CHART), China. Prehypertension was defined as systolic blood pressure (BP) of 120-139 mmHg and/or diastolic blood pressure of 80-89 mmHg.
Despite the fact that prevalence of hypertension was overall lower among PLWH than among HIV-negative people (21.1% vs. 29.1%, P < 0.001), it was similar at ages 18-29 (7.6% vs. 8.5%) and 30-44 years (17.1% vs. 18.5%) but significantly lower in PLWH at ages 45-59 (26.1% vs. 40.7%) and 60-75 years (37.1% vs. 57.3%). Prehypertension prevalence was consistently higher in PLWH across all age groups. In the model adjusting for traditional risk factors, HIV infection was associated with hypertension (adjusted odds ratio [aOR] = 1.27, 95% confidence interval: 1.04-1.55) and prehypertension (aOR = 1.77, 95% CI: 1.51-2.08), and attenuated after additional adjustment for abdominal obesity. Age-stratified analysis showed that these associations of HIV with hypertension were observed at ages 18-29 and 30-44 years and associations with prehypertension were observed at ages 18-29, 30-44 and 45-59 years only. Years since HIV diagnosis and stavudine use were the HIV-specific factors independently associated with hypertension or/and prehypertension.
HIV infection is independently associated with prehypertension and hypertension especially at younger ages, and this risk may increase as treatment becomes prolonged. Our findings reinforce the urgent necessity for active BP screening and control strategies be adopted for PLWH in China.