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Zhang, J., Teh, M., Kim, J., Eva, M. M., Cayrol, R., Meade, R., Nijnik, A., Montagutelli, X., Malo, D., Jaubert, J.
Salmonella are intracellular bacteria found in the gastrointestinal tract of mammalian, avian, and reptilian hosts.. Mouse models have been extensively used to model in vivo distinct aspects of the human Salmonella infections and have led to the identification of several host susceptibility genes. We have investigated the susceptibility of Collaborative Cross strains to intravenous infection with Salmonella Typhimurium as a model of human systemic invasive infection. In this model, strain CC042 displayed extreme susceptibility with very high bacterial loads and mortality. CC042 mice showed lower spleen weight and decreased splenocyte numbers before and after infection, affecting mostly CD8+ T cells, B cells, and all myeloid populations. Uninfected mice also had lower thymus weight with reduced total number of thymocytes and double negative and (CD4+, CD8+) double positive thymocytes. Analysis of bone marrow resident hematopoietic progenitors showed a strong bias against lymphoid primed multipotent progenitors. An F2 cross between CC042 and C57BL/6N identified two loci on chromosome 7 (Stsl6 and Stsl7) associated with differences in bacterial loads. In the Stsl7 region, CC042 carries a loss-of-function variant unique to this strain in the integrin alpha L (Itgal) gene, which causative role was confirmed by a quantitative complementation test. Notably Itgal loss of function increased the susceptibility to S. Typhimurium in a (C57BL/6JxCC042)F1 background, but not in a C57BL/6J inbred background. These results further emphasize the utility of the Collaborative Cross to identify new host genetic variants controlling susceptibility to infections and improve our understanding of the function of the Itgal gene.
Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions.
We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed.
Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis.
Rockenschaub P, Hayward A, Shallcross L.
AbstractBackgroundComorbidities like diabetes or COPD increase patients’ susceptibility to infections, but it is unclear how the onset of comorbidity impacts antibiotic use. We aimed to estimate rates of antibiotic use before and after diagnosis of comorbidity in primary care to identify opportunities for antibiotic stewardship.MethodsWe analysed UK primary care records from the Clinical Practice Research Datalink (CPRD) database. Adults registered between 2008-2015 without prior comorbidity diagnoses were eligible for inclusion. Monthly adjusted rates of antibiotic prescribing were estimated for patients with new-onset stroke, coronary heart disease, heart failure, peripheral arterial disease, asthma, chronic kidney disease, diabetes or COPD in the 12 months before and after diagnosis, and for controls without comorbidity.Results106,540 / 1,071,94 (9.9%) eligible patients were diagnosed with comorbidity. Antibiotic prescribing rates increased 1.9-2.3 fold in the 4-9 months preceding diagnosis of asthma, heart failure and COPD, before declining to stable levels within 2 months after diagnosis. A less marked trend was seen for diabetes (Rate ratio 1.55, 95%-CI: 1.48-1.61). Prescribing rates for patients with vascular conditions increased immediately before diagnosis and remained 30-39% higher than baseline afterwards. Rates of prescribing to controls increased by 17-28% in the months just before and after consultation.ConclusionsAntibiotic prescribing increased rapidly before diagnosis of conditions presenting with respiratory symptoms (COPD, heart failure, asthma), and declined afterwards. This suggests onset of respiratory symptoms may be misdiagnosed as infection. Earlier diagnosis of these comorbidities could reduce avoidable antibiotic prescribing.
Mack I, Sharland M, Berkley J, et al.
AbstractThe reduction in childhood mortality noted in trials investigating azithromycin mass drug administration (MDA) for trachoma control has been confirmed by a recent large randomized controlled trial. Population-level implementation of azithromycin MDA may lead to selection of multiresistant pathogens. Evidence suggests that repeated azithromycin MDA may result in a sustained increase in macrolide and other antibiotic resistance in gut and respiratory bacteria. Current evidence comes from standard microbiological techniques in studies focused on a time-limited intervention, while MDA implemented for mortality benefits would likely repeatedly expose the population over a prolonged period and may require a different surveillance approach. Targeted short-term and long-term surveillance of resistance emergence to key antibiotics, especially those from the World Health Organization Access group, is needed throughout any implementation of azithromycin MDA, focusing on a genotypic approach to overcome the limitations of resistance surveillance in indicator bacteria.Azithromycin mass drug administration results in a sustained increase in antimicrobial resistance when implemented at a population level. Targeted risk-based metagenomics approaches complementing traditional microbiological methods are recommended for surveillance of emerging short- and long-term antimicrobial resistance.
The classic Lemierre’s syndrome refers to a septic thrombosis of the internal jugular vein, usually caused by a Fusobacterium necrophorum infection starting in the oral cavity, and typically complicated by pulmonary emboli. However, unusual forms of the disorder have been rarely reported.
We describe an unusual case of a previously healthy 58-year-old male with Lemierre’s syndrome, manifesting with lumbar pain and fever. A thrombosis of the iliac veins and abscesses in the right iliac and the left psoas muscles was diagnosed by a computed tomography scan, together with a right lung pneumonia complicated by pleural effusion and an L4-L5 spondylodiscitis. Blood culture and pus drainage were positive for Fusobacterium nucleatum and an atypical Lemierre’s syndrome was suspected. The patient was treated with anticoagulant therapy for 12 weeks and intravenous antibiotic therapy for 6 weeks with a good evolution and resolution of the thrombosis.
This case illustrates the thrombogenic and thromboembolic tendency of Fusobacterium nucleatum and its potential invasiveness, regardless of the site of primary infection. The concept of an atypical Lemierre’s syndrome is redefined here to take into consideration non-cervical sites.
In Yemen, the underlying causes of infectious vaginitis have been neglected. Therefore, this study aimed to determine the prevalence and risk factors associated with bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomonal vaginitis (TV) among non-pregnant reproductive-aged women.
A cross-sectional study was conducted among 347 non-pregnant reproductive-aged women seeking primary healthcare in Sana’a city, Yemen. Data about sociodemographic characteristics, lifestyle-related behaviors, routine hygienic practices, menstrual care and history and type of contraceptive intake were collected using a structured questionnaire. Vaginal discharge samples were collected and examined for discharge characteristics and pH by a gynecologist. Then, samples were examined for BV, VVC and TV. Data were analyzed using suitable statistical tests.
Vaginal infections were prevalent among 37.6% of reproductive-aged women, where BV was the most prevalent (27.2%). VVC was significantly higher among symptomatic women and significantly associated with itching (P = 0.005). Using bivariate analysis, the age of
Antibiotic resistance is a leading cause of treatment failure in Helicobacter pylori infection. In Africa, there are very little data concerning the susceptibility of Helicobacter pylori isolates to antibiotics. The purpose of this study was to evaluate the resistance prevalence of Helicobacter pylori strains circulating in Cameroon, and to assess overexpression of efflux pump as a possible multi-drug resistance mechanisms.
A total of 140 H. pylori isolates were recovered from gastric biopsies of dyspeptic patients in two reference hospitals in Cameroon and analyzed for their antimicrobial susceptibility to amoxicillin, co-amoxiclav, ampicillin, penicillin, imipenem, metronidazole, rifabutin, erythromycin, clarithromycin, azithromycin, levofloxacin, ciprofloxacin, norfloxacin, tetracycline, doxycycline and minocycline. Antibiotic sensitivity was tested by disk diffusion method. Phe-Arg-naphthylamide (PAßN) was used as efflux pump inhibitor. INT broth microdilution method in supplemented Brain Heart Infusion broth was used to determine the MIC of ampicillin, amoxicillin, metronidazole, erythromycin, clarithromycin and doxycycline in the absence and the presence of PAßN against 32 selected MDR isolates.
Overall H. pylori resistance rate was 100% to ampicillin, penicillin and co-amoxiclav; 97.14% to amoxicillin, 97.85% to metronidazole, 47.85% to erythromycin, 13.57% to clarithromycin; 5, 2.86 and 0.71% to doxycycline, tetracycline and minocycline respectively. No resistance to azithromycin, rifabutin, imipenem, ciprofloxacin, norfloxacin and levofloxacin was detected among H. pylori isolates. Seventy percent (70%) of the tested isolates elicited a multiple drugs resistance pattern; 42.57% double, 15.71% triple and 5.71% quadruple drugs resistance. Metronidazole and amoxicillin were more concerned with double resistance pattern (86.76%). The spectrum of activity recorded with metronidazole, doxycycline, clarithromycin and erythromycin ranged from 0 to 100% in the absence to the presence of PAßN against the tested MDR isolates. An 8 to 128-fold increase in potency was also noticed with these antibiotics in the presence of PAßN.
With regard to the high resistance rate to both amoxicillin and metronidazole, these drugs should be avoided as components of triple therapy in our milieu. In contrast, ciprofloxacin, norfloxacin, levofloxacin and tetracyclines could be used to achieve a better eradication rate and to reduce the risk of selection of H. pylori resistant strains.
Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients.
We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses.
The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality.
Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.
Kaan Kocer, Sébastien Boutin, Alexander H. Dalpke, Klaus Heeg, Nico T. Mutters, Dennis Nurjadi
Conjugative gene transfer has been considered as one of the driving factors in transmission and dissemination of multidrug-resistant bacteria. The abundance of antimicrobial resistance genes and bacteria in the gut microbiome may provide the ideal platform for plasmid exchange. Systematic data on in vivo horizontal gene transfer (HGT) and its frequency are scarce.
Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU).
A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed.
Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] μg/L/h, P = 0.029),
CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.
The original version of this article unfortunately contained a mistake. The name of the author Mara Caroprese was rendered wrongly. The correct name is shown above.
After publication of the original article , we were notified in Table 1 a column should be removed.
Colasanti J, del Rio C.
Bendamustine, used for the treatment of indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, is known to cause prolonged myelosuppression and lymphocytopenia and has been associated with the risk of developing serious and fatal infections. While reports of localized CMV infections in asymptomatic patients exist, disseminated CMV disease has not been described.
We report the first case of disseminated CMV infection in a 75-year-old male diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with massive bone marrow infiltration. Despite 6-cycle R-bendamustine chemotherapy resulted in a good partial response, the patient developed persistent fever and severe weight loss. Analysis of cerebrospinal fluid and peripheral blood revealed the presence of CMV-DNA, while the fundus oculi examination revealed bilateral CMV retinitis. Treatment with induction and maintenance drugs was complicated by neutropenia and deterioration of renal function with electrolyte imbalance. From an immunological standpoint, we observed a profound imbalances in phenotype and function of B- and T-cell subsets, with a high proportion of circulating total, activated CD69+ and CD80+ B-cells, a low γ/δ T-cell frequency with a high proportion of CD69- and CD38-expressing cells, and hyperactivated/exhausted CD4+ and CD8+ T-cell phenotypes unable to face CMV challenge.
We hereby describe a severe form of disseminated CMV disease after R-bendamustine treatment. Our observations strongly support the careful clinical monitoring of CMV reactivation/infection in oncologic patients undergoing this therapeutic regimen.
Jae-Hoon Ko, Jeong Uk Lim, Joon Young Choi, Hong Sang Oh, Hongseok Yoo, Byung Woo Jhun, Kyungmin Huh, Kyong Ran Peck
To compare outcomes of early and delayed treatment of cidofovir for human adenovirus (HAdV) pneumonia.
Bjerum C, Ouattara A, Aboulaye M, et al.
AbstractBackgroundImproved drug regimens are needed to accelerate elimination of lymphatic filariasis in Africa. This study is to determine whether a single co-administered dose of a new triple drug regimen (ivermectin plus diethylcarbamazine plus albendazole, IDA) is non-inferior to three annual doses of ivermectin plus albendazole (IA) used in many LF endemic areas of Africa.MethodsTreatment-naïve adults with Wuchereria bancrofti microfilaremia in Agboville district of Côte d’Ivoire were randomized to receive either a single dose of IDA (N=43) or 3 annual doses of IA (N=52) in an open-label, single-blinded trial. The primary endpoint was the proportion of participants microfilaria (Mf)-negative at 36 months. Secondary endpoints were Mf clearance at 6, 12 and 24 months, inactivation of adult worm nests, and safety.ResultsAt 36 months post-treatment with IDA, 18/33 (55%, 95%CI 38-72) cleared Mf versus 33/42 (79%, 67-91) with IA (P=0.045). At 6 and 12 months IDA was superior to IA in clearing Mf (89%, CI 77-99, and 71%, CI 56-85) respectively versus 34% CI 20-48, and 26%, CI 14-42, P
P.J. Toliman, S. Phillips, S. de Jong, T. O’Neill, G. Tan, J.M.L. Brotherton, M. Saville, J.M. Kaldor, A.J. Vallely, S.N. Tabrizi
To compare the performance of dual immunostaining of p16INK4a and Ki-67 proteins performed on self-collected vaginal specimens and clinician-collected cervical specimens, as well as its performance in predicting high-grade disease.
Gökhan Cildir, John Toubia, Kwok Ho Yip, Mingyan Zhou, Harshita Pant, Pravin Hissaria, Jingxian Zhang, Wanjin Hong, Nirmal Robinson, Michele A. Grimbaldeston, Angel F. Lopez, Vinay Tergaonkar
Cildir et al. map the genomic and transcriptomic changes in human mast cells upon diverse stimuli, defining chromatin changes associated with activation and Ca2+ flux and revealing potential effectors of mast cell function. Disease-associated SNPs mapped onto cis-regulatory regions of mast cells suggest that mast cell function may impact a broad range of pathologies.
Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective.
In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection.
After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB.
We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.
Schulte B, Schmidt C, Strada L, et al.
AbstractBackgroundHepatitis C virus (HCV) infection is highly prevalent among people who inject drugs (PWID). Accurate data on HCV prevalence and incidence rates among patients receiving opioid substitution treatment (OST) are needed to estimate the current and future burden of HCV infections in this high-risk population.MethodsBaseline data from routine care were collected between October 2014 and June 2016 from randomly selected OST facilities in Germany. The primary outcome measure was the HCV status (antibody and RNA prevalence). Patients who were HCV antibody–negative at baseline were followed up after 12 months to calculate the HCV incidence rate.ResultsSixty-three facilities from 14 German Federal States provided clinical data for a total of 2466 OST patients. HCV antibody and HCV RNA prevalence were 58.8% (95% confidence interval [CI], 56.8%–60.8%) and 27.3% (95% CI, 25.5%–29.2%), respectively. At baseline, a total of 528 patients (21.4%) had previously undergone antiviral treatment. Moreover, lower HCV RNA prevalence was associated with female gender, employment, younger age, and shorter duration of OST and opioid dependence. The HCV incidence rate was 2.5 cases per 100 person-years.ConclusionsThe low HCV RNA prevalence and HCV incidence rates confirm that OST in Germany is an effective setting both for treating chronic HCV infections and for preventing new infections among PWID. Scaling up the provision of OST, HCV testing, and HCV treatment among OST patients are important public health strategies for reducing HCV infections in this high-risk population.This nationwide prospective cohort study supports the protective effects of opioid substitution treatment by confirming a low hepatitis C virus (HCV) RNA prevalence rate (27.3%) and low HCV incidence rate (2.5 cases per 100 person-years) among 2467 opioid-substituted patients in Germany.
Davy-Mendez T, Napravnik S, Wohl D, et al.
AbstractBackgroundAdvances in antiretroviral therapy, aging, and comorbidities impact hospitalization rates in HIV-infected populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes.MethodsStudy population included patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving clinical care 1996–2016. We estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine and Gray, and log-binomial regression models.Results4323 patients (29% women, 60% African-American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI] 32.4, 36.4) with a mean change of -3% per year (95% CI -4%, -2%). Thirty-day readmission risk was 18.9% (95% CI 17.7%, 20.2%) and stable over time (P=0.21 and P=0.44 for 2010–2016 and 2003–2009, respectively, compared to 1996–2002). Patients who were Black (compared to White), older, had HIV RNA >400 copies/mL, or had CD4 count
Garcia Garrido H, Mak A, Wit F, et al.
AbstractBackgroundAlthough people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations.MethodsWe identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART.ResultsIncidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts 500 cells/μL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts
F.Y.S. Kong, J.S. Hocking, C.K. Fairley
Effective treatment for Neisseria gonorrhoeae is an ongoing concern because of its growing resistance to all current recommended treatments. Infections at extragenital sites, particularly the oropharynx, are important to cure because of their role in ongoing transmission and because resistance is believed to originate at this site. This commentary reports on the results of a randomised control trial (RCT) that compared ceftriaxone 500mg plus 2g of azithromycin or gentamicin 240mg plus 2g azithromycin for the treatment of extragenital gonorrhoea infection, and found 100% microbial cure for both treatment regimens.
Salazar-Austin N, Cohn S, Lala S, et al.
AbstractBackgroundBoth pregnancy and HIV increase the risk of tuberculosis disease which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among HIV-infected individuals in high-burden settings, but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy.MethodsIn this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight and congenital anomaly) in HIV-infected pregnant women enrolled as controls in the Tshepiso study, a prospective observational cohort of HIV-infected pregnant women with and without TB disease in Soweto, South Africa from 2011-2014.ResultsThere were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed participants, 11 (16%) had an adverse pregnancy outcome compared to 23 of 82 (23%) IPT-unexposed participants. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95%CI: 1.0, 6.5; p=0.048) times higher in IPT-unexposed women compared to IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index and anemia.ConclusionsIPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for relevant demographic, clinical and HIV-related factors. These results may provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to confirm both the safety of IPT and new short-course TB preventive therapies during pregnancy.
Kariyawasam D, , Peries M, et al.
AbstractBackgroundPerinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied.MethodsAdrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1–exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells.ResultsAt week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells.ConclusionsLopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation.Giving lopinavir to infants during their first year of life induces early, asymptomatic adrenal disruption compatible with the combined inhibition of CYP 21 and CYP 17 enzymes. The impact of prolonged treatment on the adrenal glands may require further attention.
John F. McNamara, Patrick NA. Harris, Mark D. Chatfield, Penelope Lorenc, David L. Paterson
To evaluate the sequential organ failure assessment (SOFA), modified SOFA scoring and a novel performance score based on the Karnofsky score for measuring outcome following a bloodstream infection.
There have been no reports regarding the molecular characteristics, virulence features, and antibiotic resistance profiles of Staphylococcus aureus (S. aureus) from Hainan, the southernmost province of China.
Two hundred twenty-seven S. aureus isolates, consisting of 76 methicillin-resistant S. aureus (MRSA) and 151 methicillin-susceptible S. aureus (MSSA), were collected in 2013–2014 and 2018–2019 in Hainan, and investigated for their molecular characteristics, virulence genes, antibiotic resistance profiles and main antibiotic resistance genes.
Forty sequence types (STs) including three new STs (ST5489, ST5492 and ST5493), and 79 Staphylococcal protein A (spa) types were identified based on multilocus sequence typing (MLST) and spa typing, respectively. ST398 (14.1%, 32/227) was found to be the most prevalent, and the prevalence of ST398-MSSA increased significantly from 2013 to 2014 (5.5%, 5/91) to 2018–2019 (18.4%, 25/136). Seventy-six MRSA isolates were subject to staphylococcus chromosomal cassette mec (SCCmec) typing. SCCmec-IVa was the predominant SCCmec type, and specifically, ST45-SCCmec IVa, an infrequent type in mainland China, was predominant in S. aureus from Hainan. The antibiotic resistance profiles and antibiotic resistance genes of S. aureus show distinctive features in Hainan. The resistant rates of the MRSA isolates to a variety of antibiotics were significantly higher than those of the MSSA isolates. The predominant erythromycin and tetracycline resistance genes were ermC (90.1%, 100/111) and tetK (91.8%, 78/85), respectively. Eleven virulence genes, including the Panton-Valentine leukocidin (pvl) and eta, were determined, and the frequency of eta and pvl were found to be 57.3 and 47.6%. Such high prevalence has never been seen in mainland China before.
S. aureus isolates in Hainan have unique molecular characteristics, virulence gene and antibiotic resistance profiles, and main antibiotic resistance genes which may be associated with the special geographical location of Hainan and local trends in antibiotic use.
Blastocystis is one of the most common intestinal protozoa in human faecal samples with uncertain impact on public health. Studies on the prevalence of Blastocystis in HIV-positive patients are limited and dated.
A cross-sectional study was carried out involving 156 HIV-positive patients to evaluate the prevalence of Blastocystis-subtypes by molecular amplification and sequencing the small subunit rRNA gene (SSU rDNA), to identify the risk factors for its transmission, to examine the relationship between the presence of the protist and gastrointestinal disorders. Furthermore, the evaluation of the faecal calprotectin by immunoassay from a sample of subjects was performed to evaluate the gut inflammation in Blastocystis-carriers.
Blastocystis-subtypes ST1, ST2, ST3, ST4 were identified in 39 HIV-positive patients (25%). No correlation was found between the presence of the protist and virological or epidemiological risk factors. Blastocystis was more frequently detected in homosexual subjects (p = 0.037) infected by other enteric protozoa (p = 0.0001) and with flatulence (p = 0.024). No significant differences in calprotectin level was found between Blastocystis-carriers and free ones.
Blastocystis is quite common in HIV-positive patients on ART showing in examined patients 25% prevalence. Homosexual behaviour may represent a risk factor for its transmission, while CD4 count and viremia didn’t correlate with the presence of the protist. The pathogenetic role of Blastocystis remains unclear and no gut inflammation status was detected in Blastocystis-carriers. The only symptom associated with Blastocystis was the flatulence, evidencing a link between the presence of the protist and the composition and stability of gut microbiota.
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana.
This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis.
Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations – K10Q and R70Q – were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments.
Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.
Yang, D., Li, S., Stabenow, J., Zalduondo, L., Kong, Y.
Mycobacterium tuberculosis (Mtb) Rv3775 (LipE) was annotated as a putative lipase. However, its lipase activity has never been characterized and its precise role in tuberculosis (TB) pathogenesis has not been thoroughly studied to date. We overexpressed and purified the rLipE protein and demonstrated that LipE has a lipase/esterase activity. rLipE prefers medium-chain ester substrates, with the maximal activity on hexanoate. Its activity is the highest at 40 °C and pH=9. We determined that rLipE hydrolyzes trioctanoate. Using site-directed mutagenesis, we confirmed that the predicted putative activity triad residues Ser97, Gly342, and His363 are essential for the lipase activity of rLipE. Expression of lipE gene was induced under stressed conditions mimicking Mtb's intracellular niche. The gene-disrupting mutation of lipE led to significantly reduced bacterial growth inside THP-1 cells and human peripheral blood mononuclear cell derived macrophages, and attenuated Mtb infection in mice (with ~8-fold bacterial load reduction in mouse lungs). Our data suggest that LipE functions as a lipase and is important for Mtb intracellular growth and in vivo infection.
On 7th June, 2018, a primary school in Beijing, China notified Shunyi CDC of an outbreak of acute respiratory disease characterized by fever and cough among students and resulting in nine hospitalization cases during the preceding 2 weeks. We started an investigation to identify the etiologic agent, find additional cases, develop and implement control measures.
We defined probable cases as students, teachers and other staffs in the school developed fever (T ≥ 37.5 °C) with cough or sore throat; or a diagnosis of pneumonia during May 1–June 31, 2018. Confirmed cases were probable cases with Mycoplasma pneumoniae detected in oropharyngeal (OP) swabs by quantitative real-time polymerase chain reaction (qPCR). We searched case by reviewing school absenteeism records and interviewing students, teachers and staff in this school. Oropharyngeal swabs were collected from symptomatic students. Two qPCR) assay, a duplex qPCR assay, and sequencing were performed to determine the pathogen, genotype and macrolide resistance at the gene level, respectively.
From May 1st to June 31st, 2018, we identified 55 cases (36 probable and 19 confirmed), of whom 25 (45%) were hospitalized for complications. All cases were students, none of the teachers and other staffs in the school were with similar symptoms. The attack rate (AR) was 3.9% (55/1398) for all students. The cases were mainly male (58%), with an age range of 7–8 years (median: 7 years). 72% (18/25) of inpatients had radiograph findings consistent with pneumonia, and some cases were hospitalized for up to 4 weeks. Pathogen detection results indicated that Mycoplasma pneumonia (M. pneumoniae) P1 type 1 was the causative agent in this outbreak, and the strain harbored one point mutation of A to G at position 2063.
The infections by macrolide-resistant M. pneumoniae are not always mild and pneumonia was common and M. pneumoniae could causes serious complications which require long-term hospitalization. In the future infectious disease prevention and control practice, M. pneumoniae should be paid more attention. It is necessary to establish and improve the pathogen and drug resistance surveillance system in order to prevent and control such mutated strains of M. pneumoniae from causing future outbreaks or epidemics in China.
, Le Gal S, Toubas D, et al.
AbstractThe burden of nosocomial Pneumocystis infections in transplantation units in France was evaluated through a retrospective survey. Over 12 years, 16 outbreaks occurred, including 13 among renal transplant recipients (RTRs). We performed Pneumocystis jirovecii genotyping in 5 outbreaks, which suggested that specific strains may have been selected by RTRs.
Pandoraea species is a newly described genus, which is multidrug resistant and difficult to identify. Clinical isolates are mostly cultured from cystic fibrosis (CF) patients. CF is a rare disease in China, which makes Pandoraea a total stranger to Chinese physicians. Pandoraea genus is reported as an emerging pathogen in CF patients in most cases. However, there are few pieces of evidence that confirm Pandoraea can be more virulent in non-CF patients. The pathogenicity of Pandoraea genus is poorly understood, as well as its treatment. The incidence of Pandoraea induced infection in non-CF patients may be underestimated and it’s important to identify and understand these organisms.
We report a 44-years-old man who suffered from pneumonia and died eventually. Before his condition deteriorated, a Gram-negative bacilli was cultured from his sputum and identified as Pandoraea Apista by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS).
Pandoraea spp. is an emerging opportunistic pathogen. The incidences of Pandoraea related infection in non-CF patients may be underestimated due to the difficulty of identification. All strains of Pandoraea show multi-drug resistance and highly variable susceptibility. To better treatment, species-level identification and antibiotic susceptibility test are necessary.
Bergmann, R., Jentsch, M.-C., Uhlig, A., Müller, U., van der Linden, M., Rasmussen, M., Waller, A., von Köckritz-Blickwede, M., Baums, C. G.
Streptococcus equi subsp. zooepidemicus (SEZ) is an important pathogen in horses causing severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent and contact to horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among SEZ strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different SEZ strains that the M-like protein SzM is crucial for binding of fibrinogen to the bacterial surface and for survival in equine and human blood. SEZ isolates of equine and human origin were compared with regard to SzM sequences and binding of equine and human fibrinogen. The N-terminal 216 amino acids (aa) of the mature SzM were found to exhibit a high degree of diversity, but the majority of human isolates grouped in three distinct SzM clusters. Plasma protein absorption assays and flow cytometry analysis revealed that pronounced binding of human fibrinogen is a common phenotype of human SEZ isolates but much less so in equine SEZ isolates. Furthermore, binding of human fibrinogen is associated with specific SzM types. These results suggest that SzM-mediated binding of human fibrinogen is an important virulence mechanism of zoonotic SEZ isolates.
Reens, A. L., Nagy, T. A., Detweiler, C. S.
To survive and replicate during infection, pathogens utilize different carbon and energy sources depending on the nutritional landscape of their host microenvironment. Salmonella enterica serovar Typhimurium (Salmonella) is an intracellular bacterial pathogen that occupies diverse cellular niches. While it is clear that Salmonella requires access to glucose during systemic infection, data on the need for lipid metabolism are mixed. We report that Salmonella strains lacking lipid metabolism genes were defective for systemic infection of mice. Bacterial lipid import, β-oxidation and glyoxylate shunt genes were required for tissue colonization upon oral or intraperitoneal inoculation. In cultured macrophages, lipid import and β-oxidation genes were required for bacterial replication and/or survival only when the cell culture medium was supplemented with non-essential amino acids. Removal of glucose from tissue culture medium further enhanced these phenotypes and, in addition, conferred a requirement for glyoxylate shunt genes. We also observed that Salmonella needs lipid metabolism genes in pro-inflammatory but not anti-inflammatory macrophages. These results suggest that during systemic infection, the Salmonella that rely upon host lipids to replicate are within pro-inflammatory macrophages that have access to amino acids, but not glucose. An improved understanding of the host microenvironments in which pathogens have specific metabolic requirements may facilitate the development of targeted approaches to treatment.
Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys.
We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time.
The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady.
This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.
Silke Huber, Benjamin Hetzer, Roman Crazzolara, Dorothea Orth-Höller
Bloodstream infections (BSI) are a major cause of morbidity and mortality in pediatric patients. For fast and accurate diagnosis, blood culture (BC) is the gold standard. However, the procedure for blood sampling in pediatric patients, particularly the optimal blood volume, is the subject of controversy stemming from a lack of knowledge on the bacterial load and because of several obstacles such as low intravascular volume with the risk of causing anemia.
The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters.
Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF.
The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity.
The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Lack of weight gain during the first two months of treatment and HIV independently predict unsuccessful treatment outcomes in tuberculosis
14.11.2019The Journal of Infectious Diseases Advance Access
Diverse HIV-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line ART in Resource Limited Settings
14.11.2019Clinical Infectious Diseases Advance Access
Tuberculosis outbreaks among students in mainland China: a systematic review and meta-analysis
14.11.2019Latest Results for BMC Infectious Diseases
Correction to: Malaria control across borders: quasi-experimental evidence from the Trans-Kunene malaria initiative (TKMI)
14.11.2019Latest Results for Malaria Journal
Analysis on external competency assessment for malaria microscopists in China
14.11.2019Latest Results for Malaria Journal
Hvorfor anbefaler Professor Troels Lillebæk artiklen"The global prevalence of latent tuberculosis: a systematic review and meta-analysis."?
Hvad tænker Professor Lars Østergaard om"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial."?
Hvorfor synes Professor Thomas Benfield, at du bør læse"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvorfor synes Professor Niels Obel, at du bør læse"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
Hvad tænker Professor Thomas Benfield om"Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial."?
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