Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

Disseminated toxoplasmosis is a life-threatening infection in transplant recipients, which results either from reactivation of latent infection or from organ-transmitted primary infection. Preventive measures and diagnostic screening methods differ between countries and are related to the seroprevalence of Toxoplasma spp. in the general population. Here we report a case of disseminated toxoplasmosis in a heart transplant recipient with previous immunity that occurred after cotrimoxazole prophylaxis for the prevention of Pneumocystis jirovecii pneumonia was stopped. Quantitative PCR proved useful for the diagnosis and monitoring of Toxoplasma infection. Decreasing parasitic burdens in sequential samples of cerebrospinal fluid, blood, and bronchoalveolar lavage fluid correlated with a favorable outcome and allowed modulation of the immunosuppressive drug regimen. The duration of anti-Toxoplasma treatment and the need for maintenance prophylaxis are discussed, as well as prophylaxis for solid-organ transplant recipients. Although a rare event in heart transplant recipients, Toxoplasma reactivation must be investigated promptly, since early treatment improves the prognosis.Toxoplasmosis is a worldwide parasitic disease caused by the intracellular protozoan Toxoplasma gondii. After infection, acquired mostly through contaminated vegetables or undercooked meat, the parasite can persist for life, encysted in different sites such as the muscles, heart, brain, eye, and, more rarely, other organs. Whereas clinical symptoms are usually absent or mild in primarily infected immunocompetent individuals, the infection is life-threatening for immunocompromised patients (17). In transplant patients, severe or disseminated toxoplasmosis can result either from reactivation of latent infection in the recipient or from organ-transmitted infection from a seropositive donor to a seronegative recipient (6, 29), a situation where heart transplants carry the highest risk (16, 19, 22, 32). Reactivation of a chronic infection may occur in the recipient irrespective of the type of graft, but the risk is closely related to the duration and degree of immunosuppression. The risk also differs according to the immunosuppression protocol and therefore according to the graft, with hematopoietic stem cell transplantation (HSCT) carrying the highest risk (10). Furthermore, the incidence of Toxoplasma reactivation is greater in countries with higher seroprevalences. The diagnosis of acute toxoplasmosis in immunocompromised patients relies on PCR detection of parasite DNA in blood, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) samples, or biopsy specimens. Serology performs poorly in the diagnosis of reactivation of infection, due to a lack of sensitivity (in HSCT patients) or poor correlation with clinical reactivation (for solid-organ transplantation [SOT]).Here we report a case of disseminated toxoplasmosis in a previously seropositive heart transplant recipient who underwent several severe infectious complications leading to interruption of cotrimoxazole prophylaxis and subsequently to Toxoplasma reactivation. After the initial diagnosis, the infection was monitored by quantitative PCR on blood, CSF, and pulmonary samples. A decrease in parasite load correlated with a favorable clinical outcome upon treatment. Quantitative PCR is considered to be a valuable tool for the diagnosis and monitoring of acute toxoplasmosis in SOT recipients. Our results reemphasize the need to monitor Toxoplasma reactivation in seropositive recipients, particularly in countries with high seroprevalences. Potential drug regimens for anti-Toxoplasma chemoprophylaxis in heart transplant patients are discussed.     

Anti-herpesvirus prophylaxis,pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis

BackgroundHerpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients.ObjectivesTo study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT.Data sourcesCochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries.Study eligibility criteriaRandomized controlled trials (RCTs).ParticipantsAdults with haematological malignancy undergoing allo-HCT.InterventionsAntiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent.MethodsRandom-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I²). The certainty of the evidence was appraised by GRADE.ResultsWe included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7–0.99; 15 trials, I² = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34–0.85; n = 15, I² = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2–0.43; n = 13, I² = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/– pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6–1.02; n = 8, I² = 0%), CMV disease (RR 0.47, 95% CI 0.23–0.97; n = 9, I² = 30%) and HSV disease (RR 0.41, 95% CI 0.24–0.67; n = 4, I² = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events.ConclusionsAntiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.     

Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis

ObjectivesReactivation of latent toxoplasmosis may be life-threatening in haematopoietic stem cell transplant (HSCT) recipients. We conducted an 8-year-long prospective study on the diagnosis and monitoring of reactivated toxoplasmosis in paediatric HSCT recipients. The primary objective was to determine the incidence of reactivated toxoplasmosis in a setting that withholds prophylaxis until engraftment. The second objective was to identify the subgroups of HSCT recipients particularly prone to reactivation who may benefit the most from regular PCR follow-up.MethodsSerological and qPCR screening targeting the Toxoplasma 529 bp gene was performed before HSCT, and continued by weekly monitoring after HSCT for a median time of 104 days.ResultsReactivated toxoplasmosis was diagnosed in 21/104 (20.2%), predominantly in allo- (19/75) and rarely in auto-HSCT (2/29) recipients. Over 50% (14/21) of cases were diagnosed during the first month after HSCT, while awaiting engraftment without prophylaxis. Toxoplasma disease evolved in only three (14.3%, 3/21) patients, all treated by allo-HSCT. Reactivation was more frequent in patients treated for acute lymphoblastic leukaemia (3/27, p 0.03) and especially, in recipients of haploidentical stem cells (10/20, p 0.005). Seronegative status of the donor (where was known) contributed to 75% (12/16) cases of reactivated toxoplasmosis after allo-HSCT.DiscussionThe presented results show that peripheral blood-based qPCR, both before and after HSCT, is a valuable asset for the diagnosis of reactivated toxoplasmosis, whereas the results of serology in recipients should be interpreted with caution. Weekly qPCR monitoring, at least until successful engraftment and administration of prophylaxis, allows for prompt introduction of specific treatment.     

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study

ObjectivesWe aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity.MethodsThis was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2–4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity.ResultsOf 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2–4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5–163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m², 95% confidence interval (CI) 1.014–1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782–3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015–1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146–3.443, p 0.014). No serious adverse events resulting from the vaccine were reported.ConclusionsKidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.     

Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study

IntroductionAlthough solid organ transplant (SOT) recipients with pretransplant serology for cytomegalovirus (CMV-R+) are considered at intermediate risk for CMV infection post transplantation, CMV infection remains a major cause of morbidity in this population. We prospectively characterized whether having pretransplant CMV-specific cellular immunity is independently associated with controlling infection after transplantation in R + SOT recipients.MethodsA prospective cohort of consecutive R + SOT recipients that received pre-emptive treatment for CMV infection was monitored after transplantation and variables were recorded during the follow-up. The cytomegalovirus-specific T-cell immune response was characterized by intracellular cytokine staining and viral loads determined using real-time PCR.ResultsOne hundred and thirty-five R + SOT recipients were included (67 kidney, 64 liver, four liver–kidney). Only one-third of the patients (42; 31.85%) had CMV-specific T-cell immunity (CD8⁺CD69⁺INF-γ⁺ T cells >0.25%) before transplantation. Patients with negative pretransplant immunity had more CMV infection (49, 52.7% vs. 15, 35.7%; p 0.07) and received more antiviral therapy than those with immunity (32, 34.4% vs. 6, 14.3%, p 0.016). Having CMV specific immunity was an independent factor for protection from developing viraemia ≥2000 IU/mL (OR 0.276, 95% CI 0.105–0.725, p < 0.01) and lower administration of treatment (OR 0.398, 95% CI 0.175–0.905, p 0.028). Only patients with no pretransplant CMV-specific T-cell response were diagnosed with CMV-disease (8, 8.6% vs. 0, 0%, p 0.05).Discussion.Our results show that having a pretransplant CMV specific T-cell response may be associated with a lower rate of CMV viraemia and less antiviral treatment after transplantation; however, more prospective studies are needed to confirm these findings.     

The Effect of Flavonoids on Chronic Prostatitis: A Meta-analysis of Published Randomized Controlled Trials

ObjectiveTo assess the effect of flavonoids on chronic prostatitis, a meta-analysis of randomized controlled trials was performed.MethodsThrough using subject word and random word, PubMed, Scopus, Web of Science, and Cochrane Library were searched for related records up to July 2018. The response rate and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) were used to evaluate the therapeutic efficacy of the flavonoids. The Cochrane handbook for systematic reviews of interventions version was used to evaluate the quality of included studies. The model of determining odds ratio (OR) was chose according to the value of I².ResultsA total of 11 studies involving 975 subjects (experiment 516, control 459) were included. The overall OR of response rate was 0.31 (95%CI 0.11–0.89, P = 0.03). At the subgroup analysis, the OR of response rate of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) was 0.57 (95%CI 0.18–1.77, P = 0.33), while the OR of response rate of chronic bacterial prostatitis (CBP) was 0.08 (95%CI 0.02–0.33, P = 0.0005). The OR of response rate of CP/CPPS (control was placebo) was 0.29 (95%CI 0.16–0.52, P < 0.0001). The overall OR of baseline NIH-CPSI was ?0.1 (95%CI -0.61–0.41, P = 0.70). The overall OR of posttreatment NIH-CPSI was ?6.96 (95%CI -8.32～ ?5.60, P < 0.00001).ConclusionsThis meta-analysis indicates that the flavonoids may be clinically beneficial through significantly improving the response rate and NIH-CPSI in chronic prostatitis patients and short-lasting antibiotics therapy in association with the flavonoids could be a better choose for CBP. Moreover, the flavonoids therapy has an excellent safety profile with minor adverse effects.     

Prevalence and associated factors of pneumonia among under-fives with acute respiratory symptoms: a cross sectional study at a Teaching Hospital in Bushenyi District,Western Uganda

ObjectivesThis study assessed the prevalence and associated factors of pneumonia among children under-five years presenting with acute respiratory symptoms.MethodologyThis was a cross sectional study at the Pediatric Department of Kampala International University – Teaching Hospital, from the month of April to August 2019. The study included 336 children aged 2 to 59 months presenting with acute respiratory symptoms to the pediatric clinic. Pneumonia diagnosis was made according to the World Health Organization definition, modified by a chest radiograph. Structured questionnaires were used to collect data on socio-demographic, environmental and nutrition factors and multivariate logistic regression analysis using STATA version 13.0 was done to assess for the factors independently associated with pneumonia.ResultsOf the 336 children with acute respiratory symptoms, eighty-six, 86 (25.6%) had pneumonia. Factors significantly associated with pneumonia included: age below 6 months (OR=3.2, 95%CI=1.17–8.51, p=0.023), rural residence (OR=5.7, 95%CI=2.97–11.05, p <0.001), not up-to-date for age immunization status (OR=2.9, 95%CI=1.05–7.98, p=0.039), severe acute malnutrition (OR=10.8, 95%CI=2.01–58.41, p=0.006), lack of exclusive breastfeeding during the first six months (OR=2.9, 95%CI=1.53–5.53, p=0.001) and exposure to cigarette smoke (OR=3.0, 95%CI=1.35–6.80, p=0.007).ConclusionThe prevalence of pneumonia in children under-five years was high. Most of the factors associated with pneumonia are modifiable; addressing these factors could reduce this prevalence.     

Risk of lower respiratory tract infections: a genome-wide association study with Mendelian randomization analysis in three independent European populations

ObjectiveLower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide. Few studies have previously investigated genetic susceptibility and potential risk factors for LRTI.MethodsWe used data from the UK Biobank, Trøndelag Health Study (HUNT), and FinnGen to conduct a genome-wide association study (GWAS). Cases were subjects hospitalized with LRTI, and controls were subjects with no such hospitalization. We conducted stratification and interaction analyses to evaluate whether the genetic effect of LRTI differed by sex or smoking. Mendelian randomization (MR) analyses were conducted to identify the unconfounded relationship between cardiometabolic risk factors and LRTI.ResultsA total of 25 320 cases and 575 294 controls were included. The 15q25.1 locus reached genome-wide significance in the meta-analysis (rs10519203: OR 0.94, p 3.87e-11). The protective effect of effect allele of rs10519203 was present among smokers (OR 0.90, 95%CI 0.87–0.92, p 1.38e-15) but not among never-smokers (OR 1.01, 95%CI 0.97–1.06, p 5.20e-01). In MR analyses, we found that increasing body mass index (OR 1.31, 95%CI 1.24–1.40, p 3.78e-18), lifetime smoking (OR 2.83, 95%CI 2.34–3.42, p 6.56e-27), and systolic blood pressure robustly increased the risk of LRTIs (OR 1.11, 95%CI 1.02–1.22, p 1.48e-02).ConclusionA region in 15q25.1 was strongly associated with LRTI susceptibility. Reduction in the prevalence of smoking, overweight, obesity, and hypertension may reduce the disease burden of LRTIs.     

Humoral serological response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation

ObjectivesTo assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT).MethodsThis is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4–6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies.ResultsThe cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4–439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7–21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19–35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1–4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97–11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2–29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination.ConclusionA significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population.     

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study

ObjectiveTo investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT).MethodsProspective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT.ResultsWe analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21).ConclusionsCPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.     

Comparative clinical manifestations and immune effects of cytomegalovirus infections following distinct types of immunosuppression

BackgroundCytomegalovirus (CMV) infection is a well-recognised complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency virus infection, previously immunocompetent intensive care unit patients, and individuals on immunosuppressive medications for various underlying diseases.ObjectivesThis review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression.SourcesSelected peer-reviewed publications on CMV infections published until December 2021.ContentCMV infection affects various organ systems through direct cytolytic mechanisms but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations but also mitigate various immunopathological processes to reduce graft-vs.-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the intensive care unit. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation.ImplicationsA large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with human immunodeficiency virus infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomised controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.     

Clinical usefulness of gastric adenocarcinoma predictive long intergenic noncoding RNA in human malignancies: A meta-analysis

BackgroundGastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC), a newly identified lincRNA, was reported to be aberrantly expressed in several kinds of cancers and played an important role in tumor progression. This study was performed to systematically estimate the prognostic role of GAPLINC expression in cancer patients.MethodsSeveral electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for potential literature (updated to September 3, 2018). The pooled hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a fixed effects model using Stata12.0 software.ResultsThe pooled results indicated that elevated GAPLINC was significantly related to shorter overall survival (OS) (HR = 1.66, 95%CI: 1.40–1.93, p < 0.001), which was further validated using The Cancer Genome Atlas (TCGA) dataset. Furthermore, high GAPLINC expression was correlated with higher tumor grade (OR = 1.91, 95%CI: 1.35–2.70, p < 0.001), positive lymph node metastasis (OR = 2.80, 95%CI: 1.69–4.64, p < 0.001), deeper infiltration depth (OR = 2.44, 95%CI: 1.43–4.17, p = 0.001) and advanced clinical stage (OR = 3.54, 95%CI: 2.13–5.88, p < 0.001).ConclusionsOur results suggest that elevated GAPLINC was associated with poor clinical outcomes and might serve as a promising prognostic biomarker in cancer survivors.     

Predictors for treatment outcomes among patients with drug-susceptible tuberculosis in the Netherlands: a retrospective cohort study

ObjectivesWe evaluated treatment outcomes and predictors for poor treatment outcomes for tuberculosis (TB) among native- and foreign-born patients with drug-susceptible TB (DSTB) in the Netherlands.MethodsThis retrospective cohort study included adult patients with DSTB treated from 2005 to 2015 from a nationwide exhaustive registry. Predictors for unsuccessful treatment outcomes (default and failure) and TB-associated mortality were analysed using multivariate logistic regression.ResultsAmong 5674 identified cases, the cumulative incidence of unsuccessful treatment and mortality were 2.6% (n/N = 146/5674) and 2.0% (112/5674), respectively. Although most patients were foreign-born (71%; 4042/5674), no significant differences in these outcomes were observed between native- and foreign-born patients (p > 0.05). Significant predictors for unsuccessful treatment were aged 18–24 years (odds ratio (OR), 2.04; 95% CI 1.34–3.10), homelessness (OR, 2.56; 95% CI 1.16–5.63), prisoner status (OR, 5.39; 95% CI 2.90–10.05) and diabetes (OR, 2.02; 95% CI 1.03–3.97). Furthermore, predictors for mortality were aged 74–84 years (OR, 5.58; 95% CI 3.10–10.03) or ≥85 years (OR, 9.35, 95% CI 4.31–20.30), combined pulmonary and extra-pulmonary TB (OR, 4.97; 95% CI 1.42–17.41), central nervous system (OR, 120, 95% CI 34.43–418.54) or miliary TB (OR, 10.73, 95% CI 2.50–46.02), drug addiction (OR, 3.56; 95% CI 1.34–9.47) and renal insufficiency/dialysis (OR, 3.23; 95% CI 1.17–8.96).ConclusionsNative- and foreign-born patients exhibited similar TB treatment outcomes. To further reduce disease transmission and inhibit drug resistance, special attention should be given to high-risk patients.     

Primary Sjögren's syndrome and occupational risk factors: A case–control study

ObjectivesA case–control study was carried out to investigate the relation between primary Sjögren's syndrome (pSS) and occupational exposure.MethodsOne hundred seventy five cases of pSS followed up into the internal medicine departments of three French university hospitals from 2010 to 2013 were included. For each case, two age and gender matched controls were selected during the same period in the same departments. Occupational exposure was assessed retrospectively by industrial hygienists and occupational practitioners. Exposure to occupational factors such as organic solvents or silica was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment.ResultsSignificant associations with pSS were observed for dichloromethane (OR 9.28, 95%CI 2.60–33.03), perchlorethylene (OR 2.64, 95%CI 1.20–5.77) chlorinated solvents (OR 2.95, 95%CI 1.77–4.93), benzene (OR 3.30, 95%CI 1.07–10.26), toluene (OR 4.18 95%CI 1.41–12.43), white spirit (OR 3.60, 95%CI 1.39–9.33), aromatic solvents (OR 3.03, 95%CI 1.41–6.50) and any types of solvents (OR 2.76, 95%CI 1.70–4.47). Risk of pSS was significantly associated with a high cumulative exposure score of occupational exposure to toluene (OR 4.69, 95%CI 1.42–15.45), white spirit (OR 3.30, 95%CI 1.07–10.26), aromatic solvents (OR 2.50, 95%CI 1.06–5.91) and any types of solvents (OR 2.25, 95%CI 1.20–4.22).ConclusionThis work suggests the influence of occupational risk factors in the occurrence of pSS.     

Prospective long-term study on primary CMV infections in adult liver transplant (D+/R−) patients after valganciclovir prophylaxis

BackgroundCytomegalovirus (CMV) can cause severe infections in transplanted patients. To prevent CMV infection, most liver centers use prophylaxis for CMV-seronegative recipients receiving an organ from a seropositive donor (D+/R−). Valganciclovir is mostly given for 3–6 months after transplantation. However, the patients may develop primary CMV infection after the cessation of prophylaxis and late-onset CMV disease may occur.ObjectivesA prospective long-term follow-up of CMV (D+/R−) adult liver transplant recipients after 3 months valganciclovir prophylaxis was investigated.Study designOf 154 consecutive adult liver recipients transplanted from 2006 to 2009, 20 (13%) were CMV D+/R− and received antiviral prophylaxis up to 3 months after transplantation. After excluding the recipients with incomplete prophylaxis or monitoring, 13 (D+/R−) patients with follow-up of >4 years after the 3-month period of valganciclovir prophylaxis were included in the study.The patients were monitored for CMV by real-time quantitative plasma PCR.ResultsNo break-through CMV infections were recorded during the prophylaxis period. After cessation of valganciclovir prophylaxis 12/13 (90%) patients demonstrated CMV-DNAemia following a post transplantation mean interval of 165 days (range 95–320). Ten patients with high viral loads (peak viral load mean 81,510, range 1900–648950 cps/ml) were successfully treated, 6 with valganciclovir, and 4 with ganciclovir. Two patients with low level CMV-DNAemia (<1000 cps/ml) were asymptomatic and not treated. No intragraft infection was seen, but one patient developed gastrointestinal CMV infection verified from ileum biopsy. During long-term follow-up, 3 patients demonstrated low-level viral replication, but no symptomatic recurrences occurred. One patient died of bacterial sepsis, but no patient or graft was lost due to CMV.ConclusionsPrimary CMV infections after cessation of prophylaxis were common, but were successfully treated with valganciclovir or ganciclovir.     

Brucellosis and its associated risk factors to humans and domestic ruminants in Kagera Ecosystem,Tanzania

BackgroundBrucellosis is an important disease for both veterinary and public health. A study was conducted to understand the seroprevalence of brucellosis and its associated risk factors in pastoral areas of Kagera, Tanzania.MethodsSera from 156 patients with malaria-like symptoms were analyzed using the commercial rapid agglutination test (specific for B.abortus and B.melitensis detection) and Fluorescence Polarization Assay (FPA). Sera from 426 cattle, 206 goats and 197 sheep were analyzed using Rose Bengal Plate (RBPT) and Competitive ELISA (c-ELISA) tests.ResultsIn humans, overall brucellosis, B. abortus, and B. melitensis sero-prevalences were 7.7% (95%CI: 3.8–12.2%), 1.9% (95% CI: 0.4–4.5%), and 5.8 % (95%CI: 2.6–10.6%), respectively. At animal level, seropositivity was 5.9% (95%CI: 4.0–8.6%), 2.5% (95%CI: 0.8–5.7%) and 0.5% (95%CI: 0.01–2.8%) in cattle, goats and sheep, respectively. At herd level, seropositivity was 18.2% (95%CI: 12.0–25.8%) in cattle and 6.9% (95%CI: 2.2–15.3%) in small ruminants. Brucellosis was associated with assisting in parturition without wearing protective gears (OR= 5.6; p= 0.02) in humans, herds of 50–200 animals (OR= 4.2, p= 0.01) and cattle (OR=3.5; p=0.01). The knowledge of brucellosis among pastoralists (OR=0.1; p<0.01) was a protective factor.ConclusionBrucella infections could be occurring in pastoralists and domestic ruminants in Kagera. Community health education is necessary for the control of brucellosis in Tanzania.     

Infections due to alphaherpesviruses in early post-transplant period after allogeneic haematopoietic stem cell transplantation: Results of a 5-year survey

BackgroundInfections caused by human α-herpesviruses usually have a benign course with recurrencies. However, they may become dangerous in immunocompromised hosts. In this case, molecular methods constitute a reliable diagnostic tool enabling rapid assessment of the efficacy of antiviral treatment strategies.ObjectivesWe estimated the frequency of alphaherpesviral DNAemia and the viral load during early post-transplantation period after alloHSCT; we also analyzed association of the DNAemia and chosen parameters of the patients.Study designA cohort of 190 alloHSCT recipients from two hospitals in Warsaw, Poland, was examined weekly during 100-day early post-transplantation period using quantitative real time PCR assays. A total of 2475 sera samples were evaluated for the presence of α-herpesviral DNA in patients, of whom 117 (62%) received unrelated grafts, while the remaining 73 (38%) received grafts from sibling donors. All patients received standard antiviral prophylaxis with acyclovir. In the examined group, anti-HSV-1, anti-HSV-2 and anti-VZV IgGs were examined prior to transplantation,ResultsWithin the study period, DNA of α-herpesviruses was detected in 44 patients (23.2%). Most patients tested positive for HSV-1 DNA (43 patients, 22.6%), single patient for HSV-2, and no patient positive for VZV. Clinical symptoms such as pneumonia, skin changes, elevated levels of aminotransferases were observed in five patients, four of these patients presented symptoms of GvHD at the same time. (2,6%). Statistics shows that GvHD (P < 0.001) and matched unrelated donor as a source of HSCT (P = 0.048) are associated with the development of HSV-1 DNAemia.ConclusionsAlthough our data demonstrate frequent reactivation of HSV-1 in the early post-transplant period, the rate of symptomatic infections was low. We did not find association between HSV-1 viremia and mortality, but significant association with GvHD and donor source was observed.     

Effect of the immunosuppressive regimen on the incidence of cytomegalovirus infection in 378 heart transplant recipients: A single centre,prospective cohort study

BackgroundCytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection.ObjectivesTo evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols.Study designSingle centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease.ResultsMost recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p < 0.0001). Major opportunistic infections were significantly more common in groups B and C.ConclusionIn a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease.     

Microbiology of hip and knee periprosthetic joint infections: a database study

ObjectivesKnowledge of the microbiological aetiology of periprosthetic joint infection (PJI) is essential to its management. Contemporary literature from the United States on this topic is lacking. This study aimed to identify the most common microorganisms associated with types of arthroplasty, the timing of infection, and clues to polymicrobial infection.MethodsWe performed an analytical cross-sectional study of patients 18 years of age or older with hip or knee PJI diagnosed at our institution between 2010 and 2019. PJI was defined using the criteria adapted from those of the Musculoskeletal Infection Society. Cases included PJI associated with primary or revision arthroplasty and arthroplasty performed at our institution or elsewhere.ResultsA total of 2067 episodes of PJI in 1651 patients were included. Monomicrobial infections represented 70% of episodes (n = 1448), with 25% being polymicrobial (n = 508) and the rest (5%, n = 111) culture-negative. The most common group causing PJI was coagulase-negative Staphylococcus species (other than S. ludgunensis) (37%, n = 761). The distribution of most common organisms was similar regardless of arthroplasty type. The S. aureus complex, Gram-negative bacteria, and anaerobic bacteria (other than Cutibacterium species) were more likely to be isolated than other organisms in the first year following index arthroplasty (OR 1.7, 95%CI 1.4–2.2; OR 1.5, 95%CI 1.1–2.0; and OR 1.5, 95%CI 1.0–2.2, respectively). The proportion of culture-negative PJIs was higher in primary than revision arthroplasty (6.5% versus 3%, p 0.0005). The presence of a sinus tract increased the probability of the isolation of more than one microorganism by almost three-fold (OR 2.6, 95%CI 2.0–3.3).ConclusionsJoint age, presence of a sinus tract, and revision arthroplasties influenced PJI microbiology.