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Latest Results for BMC Infectious Diseases, 16.08.2019
Tilføjet 16.08.2019 17:59
A case report of Coccidioides posadasii meningoencephalitis in an immunocompetent host
Coccidioides spp. are dimorphic fungi endemic to Central America, regions of South America and southwestern USA. Two species cause most human disease: Coccidioides immitis (primarily California isolates) and Coccidioides posadasii. Coccidioidomycosis is typically acquired through inhalation of soil or dust containing spores. Coccidioidal meningitis (CM), most common in the immunocompromised host, can also affect immunocompetent hosts.
We report a case of C. posadasii meningoencephalitis in a previously healthy 42-year-old Caucasian male who returned to Canada after spending time working in New Mexico. He presented with a 3-week history of headache, malaise and low-grade fevers. He developed progressive confusion and decreasing level of consciousness following hospitalization. Evidence of hydrocephalus and leptomeningeal enhancement was demonstrated on magnetic resonance imaging (MRI) of his brain. Serologic and PCR testing of the patient's CSF confirmed Coccidioides posadasii. Despite appropriate antifungal therapy he continues to have significant short-term memory deficits and has not returned to his full baseline functional status.
Travel to endemic regions can result in disease secondary to Coccidioides spp. and requires physicians in non-endemic areas to have a high index of suspicion. Effective therapeutic options have reduced the mortality rate of CM, however, it is still associated with significant morbidity and requires life-long therapy.
Latest Results for BMC Infectious Diseases, 21.10.2019
Tilføjet 21.10.2019 15:57
A case report of multiple cerebral abscess formation complicating serogroup B Neisseria meningitidis meningitis
Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality.
We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation.
Longstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.
Latest Results for BMC Infectious Diseases, 14.09.2019
Tilføjet 14.09.2019 10:25
A rare case of Colistin-resistant Salmonella Enteritidis meningitis in an HIV-seropositive patient
Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa.
We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism.
Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.
Latest Results for BMC Infectious Diseases, 5.08.2019
Tilføjet 05.08.2019 18:17
A systematic review of cases of meningitis in the absence of cerebrospinal fluid pleocytosis on lumbar puncture
Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF.
Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject.
Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values.
A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases.
Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.
The American Journal of Tropical Medicine and Hygiene: Most Recent Articles, 2.10.2019
Tilføjet 03.10.2019 08:25
Application of Recombinant Angiostrongylus cantonensis Galectin-2 Protein for Serodiagnosis of Human Angiostrongyliasis by Immunoblotting
Angiostrongyliasis is a foodborne disease caused by a zoonotic nematode, Angiostrongylus cantonensis, which produces eosinophilic meningitis or meningoencephalitis (EOM) in humans. Definitive diagnosis is rarely possible because worms are almost never recovered from patients. Human disease can be diagnosed by clinical symptoms and serological tests. Presently, diagnosis is performed by serological detection of antibodies against specific somatic antigens (molecular mass 29–31 kDa) extracted from female worms. The life cycle of A. cantonensis must be maintained in the laboratory to provide a source of this diagnostic antigen. Here, we cloned and expressed recombinant A. cantonensis galectin-2 (rAcGal2) corresponding to a 31-kDa antigenic peptide. Recombinant protein was purified and used in immunoblot tests, which showed reactions with human serum panels consisting of six confirmed angiostrongyliasis and 24 clinically diagnosed cases of EOM-associated with angiostrongyliasis, 160 samples from patients with other parasitic infections, and 30 samples from normal healthy subjects. Accuracy, sensitivity, specificity, and positive and negative predictive values were 95.0%, 93.3%, 95.3%, 75.7%, and 98.9%, respectively. The test was nonreactive with sera of human gnathostomiasis and cysticercosis, two diseases that could present similar neurological symptoms. Recombinant AcGal2 has potential as a diagnostic antigen and could replace native parasite antigens in further development of an angiostrongyliasis serodiagnostic test kit.
Latest Results for BMC Infectious Diseases, 15.10.2019
Tilføjet 15.10.2019 18:19
Case report: chronic relapsing cryptococcal meningitis in a patient with low mannose-binding lectin and a low naïve CD4 cell count
Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category.
A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts.
We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis.
Latest Results for BMC Infectious Diseases, 13.08.2019
Tilføjet 13.08.2019 18:49
Clinical benefits of FilmArray meningitis-encephalitis PCR assay in partially-treated bacterial meningitis in Israel
Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM.
Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay.
The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01).
The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis.
The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center (0378–17-TLV, 10/17/2017) and Rabin Medical Center (0270–18-RMC, 11/11/2018) Ethics committees and conforms to recognized standards.
Latest Results for BMC Infectious Diseases, 27.11.2019
Tilføjet 28.11.2019 02:11
Clinical diversity of invasive cryptococcosis in AIDS patients from central China: report of two cases with review of literature
Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis.
We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient’s treatment, but unfortunately, he died three days later.
Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy.
Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.
Clinical Infectious Diseases Advance Access, 12.07.2019
Tilføjet 15.07.2019 18:37
Community-Acquired Bacterial Meningitis In Adults With Cerebrospinal Fluid Leakage
AbstractBackgroundCerebrospinal fluid (CSF) leakage is a risk factor for developing bacterial meningitis.Materials/methodsWe analyzed episodes of community-acquired bacterial meningitis associated with CSF leakage from a prospective nationwide cohort study.ResultsCSF leakage was identified in 65 episodes of 2022 episodes (3%) in 53 patients. The cause of CSF leakage was identified in 49 of 65 episodes (75%), most and most commonly consisted of ear-nose-throat surgery (19 of 49 episodes [29%]) and remote head trauma (15 of 49 episodes [23%]). The episode was a recurrent meningitis episode in 38 patients (59%). Of the recurrent episodes, 27 had known CSF leakage (71%) of whom 20 (53%) had previous surgery aiming to close the leak. Nine patients (38%) with known CSF leakage had been vaccinated (23-valent pneumococcal vaccine in 9 patients, meningococcal serogroup C vaccine in 2, meningococcal serogroup A and Haemophilus influenzae type b vaccine each in 1 patient). Streptococcus pneumoniae was cultured in 33 episodes (51%) and H. influenzae in 11 episodes (17%). Most common pneumococcal serotype were 3 (4 episodes), 35B, 9N, 38 and 15C (each 2 episodes). H. influenzae was unencapsulated in all 10 episodes with known capsule type. The outcome was unfavorable in 8 episodes (12%) and no patient died.ConclusionBacterial meningitis in patients with CSF leakage have a high recurrence rate, despite surgical repair or vaccination, and outcome is generally favorable. CSF leakage should be suspected in patients with bacterial meningitis presenting with liquorrhoea, recurrent meningitis or with disease caused by H. influenzae.
Clinical Microbiology and Infection,
Tilføjet 14.09.2019 00:31
Community-acquired pneumonia in patients with bacterial meningitis: A prospective nationwide cohort study
Pneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission.
The Lancet Infectious Diseases,
Tilføjet 10.11.2019 18:52
Correction to Lancet Infect Dis 2019; 19: 429–38
Simon F, Boutin J-P, Milleliri J-M, Tournier J-N. Cerebrospinal meningitis: lessons learnt from Africa. Lancet Infect Dis 2019; 19: 1056—In this Correspondence, the email address of the corresponding author should be firstname.lastname@example.org. This correction has been made to the online version as of Oct 9, 2019.
Clinical Infectious Diseases Advance Access, 3.11.2019
Tilføjet 04.11.2019 04:32
Cryptococcal Antigenemia in HIV therapy-experienced Ugandans with Virologic Failure
AbstractBackgroundDetectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization (WHO) recommends CrAg screening for HIV infected people with CD4
Clinical Infectious Diseases Advance Access, 1.09.2019
Tilføjet 01.09.2019 21:04
Cytomegalovirus viremia associated with increased mortality in cryptococcal meningitis in sub-Saharan Africa
AbstractBackgroundCryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced HIV/AIDS. Cytomegalovirus (CMV) viremia may be associated with increased mortality in HIV-infected persons with tuberculosis. It is unknown if concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections.MethodsWe prospectively enrolled HIV-infected Ugandans with cryptococcal meningitis from 2010–2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival among those with and without CMV viremia.ResultsOf 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL; IQR, 259–2390). All samples tested were positive on IgG serology. The median CD4+ T cell count was 19 cells/µL (IQR, 9–70) and did not differ by the presence of CMV viremia (P=.47). The 10-week mortality was 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (Hazard Ratio=2.19; 95%CI, 1.07–4.49; P=.03), which remained significant after multivariate adjustment for known risk factors of mortality (adjusted Hazard Ratio=3.25; 95%CI, 1.49–7.10; P=.003). Serum and CSF cytokine levels were generally similar, and cryptococcal antigen-specific immune stimulation responses did not differ.ConclusionHalf of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with over two-fold higher mortality. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect underlying immune dysfunction (i.e. cause vs. effect).
AAC Accepts: Articles Published Ahead of Print,
Tilføjet 06.08.2019 04:07
Delamanid Central Nervous System Pharmacokinetics in Tuberculous Meningitis in Rabbits and Humans [Experimental Therapeutics]
Central nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug (MDR-) and extensively drug resistant-tuberculous meningitis (TBM), specifically, is nearly uniformly fatal, with little information to guide treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated TB drug with a low minimal inhibitory concentration (1-12 ng/mL) against Mycobacterium tuberculosis. It is used for pulmonary MDR-TB, but CNS pharmacokinetic (PK) data in TBM are not available. In the present study, we measured DLM concentrations in the brain and cerebrospinal fluid (CSF) of six rabbits, with and without experimentally-induced TBM, receiving single-dose DLM. We report steady-state CSF concentrations from three patients receiving DLM as part of multidrug-treatment who underwent therapeutic drug monitoring. Drug was quantified using LCMS/MS. In rabbits and humans, mean CSF concentrations (rabbit [1.26 ng/mL at 9h, 0.47 ng/mL at 24h]; human [48 ng/mL at 4h]) were significantly lower than plasma (rabbits [124 ng/mL at 9h, 14.5 ng/mL at 24h]; human [726 ng/mL at 4h]), but estimated free CSF/plasma ratio were >1. In rabbits, brain DLM concentrations were 5-fold higher than in plasma (mean 518 ng/mL at 9h, 74.0 ng/mL at 24h). All patients with XDR-TBM receiving DLM experienced clinical improvement and survival. Collectively, these results suggest that DLM achieves adequate concentrations in brain tissue. Despite relatively low total CSF drug levels, free drug may be sufficient and DLM may have a role in treating TBM. More studies are needed to develop a fuller understanding of its distribution over time with treatment, and clinical effectiveness.
Clinical Microbiology and Infection,
Tilføjet 21.07.2019 08:12
Diagnostic accuracy of droplet digital PCR analysis of cerebrospinal fluid for tuberculous meningitis in adult patients
Tuberculous meningitis (TBM) is still difficult to diagnose. Digital PCR (dPCR) is a novel method which can quantify trace nucleic acids. This study sought to evaluate the diagnostic accuracy of dPCR analysis of cerebrospinal fluid (CSF) for TBM.
Clinical Microbiology and Infection,
Tilføjet 22.11.2019 11:42
Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis
The FilmArray® Meningitis/Encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.
The American Journal of Tropical Medicine and Hygiene: Most Recent Articles, 7.08.2019
Tilføjet 08.08.2019 08:39
Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis
In this study, we investigated the diagnostic utility of the cytokine profile of the cerebrospinal fluid (CSF) and enzyme-linked immunospot (ELISPOT) assays of patients with suspected tuberculous meningitis (TBM). We prospectively enrolled adult patients with suspected TBM, and CSF specimens were analyzed for 18 cytokines/chemokines and soluble programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1). Enzyme-linked immunospot assays were performed on mononuclear cells from the CSF (CSF-MCs) and peripheral blood (PBMCs). A total of 87 patients with meningitis, including 42 TBM-suspected patients and 45 non-TBM patients, were enrolled. Excluding the 32 patients with possible TBM, 10 patients with TBM and 45 patients with non-TBM were finally analyzed. Levels of adenosine deaminase (ADA), interleukin 12 subunit β (IL-12p40), IL-13, macrophage inflammatory protein α (MIP-1α), and soluble PD-1 and PD-L1 in the CSF were significantly higher in the TBM group than in the non-TBM group (P < 0.05). The optimal cutoff values for the sensitivities and specificities of the test methods for diagnosing TBM with small samples of 10 cases of definite or probable TBM were as follows: ADA > 6.95 U/L, 70% and 81%; IL-12p40 > 52.04 pg/mL, 80% and 73%; IL-13 > 0.44 pg/mL, 90% and 47%; MIP-1α > 8.83 pg/mL, 80% and 62%; soluble PD-1 > 35.87 pg/mL, 80% and 63%; soluble PD-L1 > 24.19 pg/mL, 80% and 61%; CSF-MC ELISPOT > 13.5 spots/250,000 CSF-MC, 30% and 91%; and PBMC ELISPOT > 14 spots/250,000 PBMCs, 50% and 78%, respectively. Therefore, CSF IL-12p40, IL-13, MIP-1α, and soluble PD-1 and PD-L1 concentrations appear to be useful adjuncts for diagnosing TBM.
The American Journal of Tropical Medicine and Hygiene: Most Recent Articles, 7.08.2019
Tilføjet 08.08.2019 08:39
Early Mortality among Immunocompetent Patients of Tuberculous Meningitis: A Prospective Study
Most deaths in tuberculous meningitis occur in the early part of the illness. We assessed the determinants of early deaths, occurring within 2 months of intensive therapy. We prospectively included consecutive newly diagnosed adults with HIV-negative tuberculous meningitis. Patients were given WHO-recommended antituberculosis treatment and were followed up for 9 months. We enrolled 152 patients. A total of 26 deaths were recorded during 2 months. The logistic regression analysis revealed that papilledema (P = 0.029, odds ratio (OR) = 4.8 [1.2–19.8]), increasing age (P = 0.001, OR = 1.07 [1.03–1.1]), stage-III disease (Glasgow coma scale score ≤ 10; P = 0.01, OR = 4.2 [1.4–12.3]), and hydrocephalus (P = 0.003, OR = 8.4 [2.1–33.6]) were independently associated with death. In addition, cerebral infarcts (P = 0.012, OR = 5.6 [1.5–21.3]), paraparesis (P = 0.004, OR = 8.8 [2.02–38.1]), and age (P = 0.005, OR = 1.05 [1.02–1.09]) were associated with poor functional outcome. In conclusion, disease severity predicts early deaths in tuberculous meningitis.
Emerging Infectious Diseases Journal, 25.07.2019
Tilføjet 18.08.2019 15:27
Effect of Pneumococcal Conjugate Vaccines on Pneumococcal Meningitis, England and Wales, July 1, 2000–June 30, 2016
International Journal of Infectious Diseases,
Tilføjet 16.09.2019 09:02
Efficacy of Ventriculoperitoneal Shunting in Patients of Cryptococcal Meningitis with Intracranial Hypertension
AAC Accepts: Articles Published Ahead of Print,
Tilføjet 12.11.2019 03:24
Emergence of ceftriaxone resistance during a pneumococcal meningitis with fatal evolution [Challenging Clinical Case In Antimicrobial Resistance]
We report a case of a 62-year old man treated for a Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After a neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in serum and CSF. S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid ten days after the isolation of the first strain. Isolates analysis showed that a mutation of penicillin-binding proteins in PBP2x has occurred under treatment.
Latest Results for BMC Infectious Diseases, 28.11.2019
Tilføjet 28.11.2019 23:53
High prevalence of group B streptococcus ST17 hypervirulent clone among non-pregnant patients from a Hungarian venereology clinic
Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed.
Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR.
The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene.
21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele.
The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections.
This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.
Trends in Microbiology,
Tilføjet 17.07.2019 07:57
How BspC from Streptococcus agalactiae Interacts with Host Vimentin during Meningitis
Streptococcus agalactiae meningitis is a frequent neonatal disease associated with high mortality and permanent neurological damage. Deng et al. (PLoS Pathog., 2019) now show that interactions between the bacterial protein BspC and host cell vimentin participate in the process of invasion of the meninges by this bacterial pathogen.
The American Journal of Tropical Medicine and Hygiene: Most Recent Articles, 6.11.2019
Tilføjet 07.11.2019 05:41
Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation
Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used the cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures per year, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin, and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics, and lessen the health and economic burden of AMR.
Clinical Microbiology and Infection,
Tilføjet 19.10.2019 23:22
Improving the diagnosis of tuberculous meningitis: good, but not good enough
Tuberculosis (TB) is the leading infectious cause of death globally. Meningitis accounts for 1-2% of TB cases (more in HIV-endemic settings), but kills or disables up to 50% or more of those affected . Tuberculous meningitis (TBM) is notoriously difficult to diagnose with conventional microbiological techniques due to the scarcity of bacilli and Mycobacterium tuberculosis DNA.
The American Journal of Tropical Medicine and Hygiene: Most Recent Articles, 6.11.2019
Tilføjet 07.11.2019 05:41
Intravenous Steroid Days and Predictors of Early Oral Steroid Administration in Tuberculous Meningitis: A Retrospective Study
Intravenous (IV) dexamethasone is recommended for 14 days in stage 1 and 28 days in stage 2/3 tuberculous meningitis (TBM). We used a different steroid protocol. We shifted TBM patients to oral steroids after 48 hours of sustained improvement on IV steroids (oral group). Patients who worsened after shifting to oral steroids were reinitiated on IV steroids. Once they showed a consistent improvement for 48 hours, the IV steroids were overlapped with oral steroids for 7–10 days to taper off IV steroids (overlap group). We compared total IV steroid days in our patients with the recommended treatment and identified predictors that favored the oral group. This was a retrospective study. We included 98 patients with TBM (66 in the overlap group and 32 in the oral group) from January 2013 to July 2018. The median IV steroid days were 9 days (interquartile range of 4–12; 2–3.5 days in the oral group and 10–11.5 days in the overlap group). The mortality rate was 6.1%. The logistic regression model showed that TBM patients with basal exudate, tuberculoma, and modified Rankin scale (mRS) < 3 had a higher probability for going to the oral group. We conclude that total IV steroid days can be reduced in TBM patients by our method of steroid use. Presence of basal exudates and tuberculoma may favor early shifting from IV to oral steroid, whereas higher mRS may require a relatively longer course of IV steroid.
Latest Results for BMC Infectious Diseases, 29.11.2019
Tilføjet 29.11.2019 21:01
Meningitis gone viral: description of the echovirus wave 2013 in Germany
Aseptic meningitis epidemics may pose various health care challenges.
We describe the German enterovirus meningitis epidemics in the university hospital centers of Düsseldorf, Cologne and Berlin between January 1st and December 31st, 2013 in order to scrutinize clinical differences from other aseptic meningitis cases.
A total of 72 enterovirus (EV-positive) meningitis cases were detected in our multicenter cohort, corresponding to 5.8% of all EV-positive cases which were voluntarily reported within the National Enterovirus surveillance (EVSurv, based on investigation of patients with suspected aseptic meningitis/encephalitis and/or acute flaccid paralysis) by physicians within this period of time. Among these 72 patients, 38 (52.8%) were enterovirus positive and typed as echovirus (18 pediatric and 20 adult cases, median age 18.5 years; echovirus 18 (1), echovirus 2 (1), echovirus 30 (31), echovirus 33 (1), echovirus 9 (4)). At the same time, 45 aseptic meningitis cases in our cohort were excluded to be due to enteroviral infection (EV-negative). Three EV-negative patients were tested positive for varicella zoster virus (VZV) and 1 EV-negative patient for herpes simplex virus 2. Hospitalization was significantly longer in EV-negative cases. Cerebrospinal fluid analysis did not reveal significant differences between the two groups. After discharge, EV-meningitis resulted in significant burden of sick leave in our pediatric cohort as parents had to care for the children at home.
Voluntary syndromic surveillance, such as provided by the EVSurv in our study may be a valuable tool for epidemiological research. Our analyses suggest that EV-positive meningitis predominantly affects younger patients and may be associated with a rather benign clinical course, compared to EV-negative cases.
Current Opinion in Infectious Diseases - Published Ahead-of-Print, 16.07.2019
Tilføjet 22.07.2019 17:27
Meningitis vaccines in children: what have we achieved and where next?
Purpose of review
This review highlights the recent impacts of vaccines against the major bacterial causes of meningitis in children, and the challenges for further prevention of bacterial meningitis, with a focus on Streptococcus pneumoniae, Neisseria meningitidis and group B Streptococcus.
Conjugate vaccines against S. pneumoniae and N. meningitidis have resulted in dramatic reductions in bacterial meningitis globally where they have been used. Recent licensure and use of capsular group B meningococcal protein vaccines have further reduced meningococcal meningitis in infants, young children and adolescents for countries with endemic disease and during outbreaks.
Existing vaccines to prevent bacterial meningitis in children should be utilized in countries with significant numbers of cases of pneumococcal and/or meningococcal meningitis. Vaccines, which are able to protect against more than 13 serotypes of S. pneumoniae are in clinical trials and should be able to further reduce pneumococcal meningitis cases. Cost effective meningococcal vaccines against non-A capsular groups are needed for low-resource countries. There remains an urgent need for a vaccine against group B Streptococcus, which is a major cause of neonatal meningitis globally and for which no vaccine currently exists.
Correspondence to Manish Sadarangani, Vaccine Evaluation Center, BC Children's Hospital Research Institute, 950 West 28th Avenue, Vancouver BC, Canada V5Z 4H4. Tel: +1 604 875 2422; e-mail: email@example.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
AAC Accepts: Articles Published Ahead of Print,
Tilføjet 10.09.2019 08:15
Meropenem versus cefotaxime and ampicillin as empirical antibiotic treatment in adult bacterial meningitis: A quality registry study 2008-2016 [Clinical Therapeutics]
Objectives Cefotaxime, alone or with ampicillin, is frequently used as empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM.Methods The study was based on data from the Swedish quality register for ABM between January 2008 and December 2016. A propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30-days was the primary outcome.Results The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. After propensity score matching the 30-day mortality was 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases the OR for 30-day mortality for meropenem vs. cefotaxime plus ampicillin was 1.15 (CI: 0.41–3.22; p=0.79). The OR for 90-day mortality was 1.47 (CI: 0.62–3.52; p=0.38), and for unfavorable outcome 1.10 (CI: 0.75–1.63; p=0.62).Conclusions The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as empirical treatment for the majority of patients with ABM.
Clinical Infectious Diseases Advance Access, 30.10.2019
Tilføjet 30.10.2019 23:15
Model-based meta-analysis of rifampicin exposure and mortality in Indonesian tuberculosis meningitis trials
AbstractBackgroundIntensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.MethodsAn individual patient meta-analysis was performed on data from three Indonesian randomized controlled phase II trials comparing oral rifampicin 450mg (~10mg/kg) to intensified regimens including 750-1350mg orally, or a 600mg intravenous infusion. Pharmacokinetic data from plasma and CSF was analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.ResultsPharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured two disposition-compartments, saturable clearance and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5% [95%CI 4.4-6.4]) and half-life for distribution plasma to CSF (2.1 h [1.3-2.9]). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 drop-outs) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from ~50% to ~70% upon increasing the oral rifampicin dose from 10 to 30mg/kg, and that higher doses would further increase survival.ConclusionsHigher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30mg/kg to be investigated in phase III clinical trials.
Latest Results for BMC Infectious Diseases, 18.09.2019
Tilføjet 18.09.2019 15:58
Molecular characteristics of group B Streptococcus isolates from infants in southern mainland China
Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known.
This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged
Latest Results for BMC Infectious Diseases, 10.07.2019
Tilføjet 10.07.2019 17:15
Nasopharyngeal carriage of Streptococcus pneumoniae serotypes among children in India prior to the introduction of pneumococcal conjugate vaccines: a cross-sectional study
Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and other serious infections among children in India. India introduced the 13-valent pneumococcal conjugate vaccine (PCV) in several states in 2017, and is expected to expand to nationwide coverage in the near future. To establish a baseline for measuring the impact of PCV in India, we assessed overall and serotype-specific nasopharyngeal carriage in two pediatric populations.
A cross-sectional study was conducted in Palwal District, Haryana, from December 2016 to July 2017, prior to vaccine introduction. Children 2–59 months of age with clinical pneumonia seeking healthcare and those in the community with no clear illness were targeted for enrollment. A nasopharyngeal swab was collected and tested for pneumococcus using conventional culture and sequential multiplex PCR. Isolates were tested for antimicrobial resistance using an E test. Children were considered colonized if pneumococcus was isolated by culture or PCR. The prevalence of pneumococcal and serotype-specific colonization was compared between groups of children using log-binomial regression.
Among 601 children enrolled, 91 had clinical pneumonia and 510 were community children. The proportion colonized with S. pneumoniae was 74.7 and 54.5% among children with clinical pneumonia and community children, respectively (adjusted prevalence ratio: 1.38; 95% confidence interval: 1.19, 1.60). The prevalence of PCV13 vaccine-type colonization was similar between children with clinical pneumonia (31.9%) and community children (28.0%; p = 0.46). The most common colonizing serotypes were 6A, 6B, 14, 19A, 19F, and 23F, all of which are included in the PCV13 vaccine product. Antimicrobial resistance to at least one drug was similar between isolates from children with clinical pneumonia (66.1%) and community children (61.5%; p = 0.49); while resistance to at least two drugs was more common among isolates from children with clinical pneumonia (25.8% vs. 16.4%; p = 0.08). Resistance for all drugs was consistently higher for PCV13 vaccine-type serotypes compared to non-vaccine serotypes in both groups.
This study provides baseline information on the prevalence of serotype-specific pneumococcal colonization among children prior to the introduction of PCV in India. Our results suggest a role for pneumococcal vaccines in reducing pneumococcal colonization and antimicrobial resistant isolates circulating in India.
The Journal of Infectious Diseases Advance Access, 21.08.2019
Tilføjet 22.08.2019 07:20
Notch1 signalling pathway promotes proliferation and mediates differentiation direction in hippocampus of Streptococcus pneumonia meningitis rats
AbstractBackgroundStreptococcus pneumonia meningitis (PM) is a major cause of childhood neurological deficits. Although the Notch1 signalling pathway regulates neurogenesis and neuroinflammation, we know little about its expression or influence on hippocampal neurogenesis and gliogenesis during PM.MethodsWe used immunofluorescence and western blots to detect Notch1 signalling expression during experimental PM. Through double-labelling immunofluorescence, we investigated proliferation and differentiation in the dentate gyrus (DG) in PM before and after treatment with exogenous Notch1 activator (Jagged1) and inhibitor (IMR-1).ResultsOur results showed that Notch1 was activated after 24 h in PM. Compared with the PBS control, Jagged1 increased the proliferation of neural stem cells and progenitor cells (NS/PCs) in DG. After 14 and 28 d of meningitis, astrocyte differentiation increased compared with control. Astrocyte differentiation was higher in the Jagged1 versus the PBS group. In contrast, IMR-1 increased neuronal differentiation but decreased astrocyte differentiation compared with DMSO treatment.ConclusionUnder PM, Notch1 signalling promotes NS/PC proliferation and astrocyte differentiation in DG, while decreasing neuronal differentiation. Transient activation of the Notch1 signalling pathway explains the reactive gliogenesis and limited neuronal differentiation observed in PM.
International Journal of Infectious Diseases,
Tilføjet 20.11.2019 13:29
Phenotypic and genotypic characterization of meningococcal isolates in Tunis-Tunisia: High diversity and impact on vaccination strategies
Neisseria meningitidis (The meningococcus, Men) is a Gram-negative bacterium that cause meningitis and/or septicaemia. The virulence of Men is linked to many bacterial factors but the major one is the capsule. Based on the structure and the expression of the capsule, meningococcal strains are classified into 12 serogroups but Invasive Meningococcal Disease (IMD) is linked almost only to six of them: A, B, C, W, Y or X causing sporadic cases, small clusters or epidemics all over the world. However, the distribution of meningococcal serogroups varies in time and from country to another (Acevedo et al., 2019).
AAC Accepts: Articles Published Ahead of Print,
Tilføjet 01.10.2019 07:05
Spore Germination as a Target for Antifungal Therapeutics [Experimental Therapeutics]
Spores are required for long-term survival of many organisms, including most fungi. For the majority of fatal human fungal pathogens, spore germination is the key process required to initiate vegetative growth and ultimately cause disease. Because germination is required for pathogenesis, the process could hold fungal-specific targets for new antifungal drug development. Compounds that inhibit germination could be developed into high efficacy, low-toxicity drugs for use in the prevention and/or treatment of fungal spore-mediated diseases. To identify drugs with the ability to inhibit pathogenic fungal spore germination, we developed a novel luciferase-based germination assay, using spores of the meningitis-causing yeast Cryptococcus. We screened the L1300 Selleck Library of FDA-approved drugs and identified 27 that inhibit germination. Of these, 22 inhibited both germination and yeast growth, and 21 have not been previously indicated for use in the treatment of fungal diseases. We quantitated the inhibition phenotypes of 10 specific germination/growth inhibitors in detail and tested one drug, the antiparasitic compound pentamidine, in our mouse intranasal model of cryptococcal infection. We discovered that pentamidine was effective at reducing lung fungal burdens when used in either prophylaxis (before infection) or treatment (after establishing an infection). Due to its efficacy in vivo and low intranasal toxicity, pentamidine is a lead candidate for repurposing for broader use as an antigerminant to prevent spore-mediated disease in immunocompromised patients. Not only does pentamidine provide an opportunity for prophylaxis against fungal spores, but it also provides proof of concept for targeting pathogenic spore germination for antifungal drug development.
Latest Results for BMC Infectious Diseases, 11.11.2019
Tilføjet 11.11.2019 15:10
Streptococcus Oralis meningitis from right sphenoid Meningoencephalocele and cerebrospinal fluid leak
Streptococcus oralis belongs to the Streptococcus mitis group and is part of the normal flora of the nasal and oropharynx (Koneman et al., The Gram-positive cocci part II: streptococci, enterococci and the ‘Streptococcus-like’ bacteria. Color atlas and textbook of diagnostic microbiology, 1997). Streptococcus oralis is implicated in meningitis in patients with decreased immune function or from surgical manipulation of the central nervous system. We report a unique case of meningitis by Streptococcus oralis in a 58-year-old patient with cerebral spinal fluid leak due to right sphenoid meningoencephalocele.
A 58-year-old female presented in the emergency department due to altered mental status, fevers, and nuchal rigidity. Blood cultures were positive for Streptococcus oralis. Magnetic resonance stereotactic imaging of head with intravenous gadolinium showed debris in lateral ventricle occipital horn and dural thickening/enhancement consistent with meningitis. There was also a right sphenoidal roof defect, and meningoencephalocele with cerebrospinal fluid leak as a result. The patient was treated with ceftriaxone and had endoscopic endonasal repair of defect. She had complete neurologic recovery 3 months later.
Cerebrospinal fluid leak puts patients at increased risk for meningitis. Our case is unique in highlighting Streptococcus oralis as the organism implicated in meningitis due to cerebrospinal fluid leak.
Emerging Infectious Diseases Journal, 15.11.2019
Tilføjet 16.11.2019 07:27
Streptococcus suis–Associated Meningitis, Bali, Indonesia, 2014–2017
Clinical Infectious Diseases Advance Access, 26.09.2019
Tilføjet 27.09.2019 14:47
The Clinical Picture and Severity of Invasive Meningococcal Disease Serogroup W Compared With Other Serogroups in the Netherlands, 2015–2018
AbstractBackgroundAn increase in invasive meningococcal disease (IMD) serogroup W (IMD-W) cases caused by sequence type-11 clonal complex (cc11) was observed from October 2015 in the Netherlands. We compared the clinical picture and disease outcome of IMD-W cases with other serogroups, adjusting for host characteristics.MethodsWe included IMD cases reported from January 2015 to June 2018 in the Netherlands and assessed clinical manifestation and symptoms at disease onset and calculated case fatality rates (CFRs). We used logistic regression to compare clinical manifestations and mortality of IMD-W with IMD caused by meningococci serogroup B, Y, or C, adjusting for age, gender, and comorbidities.ResultsA total of 565 IMD cases were reported, of which 204 were IMD-W, 270 IMD-B, 63 IMD-Y, and 26 IMD-C. Most IMD-W isolates belonged to cc11 (93%; 175/188). Compared with other serogroups, IMD-W patients were diagnosed more often with septicemia (46%) or pneumonia (12%) and less often with meningitis (17%, P < .001). IMD-W cases presented more often with respiratory symptoms (45%, P < .001); 16% of IMD-W patients presented with diarrhea without IMD-specific symptoms (P = .061). The CFR for IMD-W was 16% (32/199, P < .001). The differences between IMD-W and other serogroups remained after adjusting for age, gender, and comorbidities.ConclusionsThe atypical presentation and severe outcome among IMD-W cases could not be explained by age, gender, and comorbidities. Almost all our IMD-W cases were caused by cc11. More research is needed to identify the bacterial factors involved in clinical presentation and severity of IMD-W cc11.
IAI Accepts: Articles Published Ahead of Print,
Tilføjet 19.11.2019 19:34
The host GTPase Arf1 and its effectors AP1 and PICK1 stimulate actin polymerization and exocytosis to promote entry of Listeria monocytogenes [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]
Listeria monocytogenes is a food-borne bacterium that causes gastroenteritis, meningitis, or abortion. Listeria induces its internalization (entry) into some human cells through interaction of the bacterial surface protein InlB with its host receptor, the Met tyrosine kinase. InlB and Met promote entry through stimulation of localized actin polymerization and exocytosis. How actin cytoskeletal changes and exocytosis are controlled during entry is not well understood. Here we demonstrate important roles for the host GTPase Arf1 and its effectors AP1 and PICK1 in actin polymerization and exocytosis during InlB-dependent uptake. Depletion of Arf1 by RNAi or inhibition of Arf1 activity using a dominant negative allele impaired InlB-dependent internalization, indicating an important role for Arf1 in this process. InlB stimulated an increase in the GTP-bound form of Arf1, demonstrating that this bacterial protein activates Arf1. RNAi and immunolocalization studies indicated that Arf1 controls exocytosis and actin polymerization during entry by recruiting the effectors AP1 and PICK1 to the plasma membrane. In turn, AP1 and PICK1 promoted plasma membrane translocation of both Filamin A (FlnA) and Exo70, two host proteins previously found to mediate exocytosis during InlB-dependent internalization (M. Bhalla, H. Van Ngo, G.C. Gyanwali, and K. Ireton, Infect. Immun. 87: e00689-18. doi: 10.1128/IAI.00689-18). PICK1 mediated recruitment of Exo70, but not FlnA. Collectively these results indicate that Arf1, AP1, and PICK1 stimulate exocytosis by redistributing FlnA and Exo70 to the plasma membrane. We propose that Arf1, AP1, and PICK1 are key coordinators of actin polymerization and exocytosis during infection of host cells by Listeria.
Emerging Infectious Diseases Journal, 30.08.2019
Tilføjet 16.09.2019 09:02
Two Cases of Borrelia miyamotoi Meningitis, Sweden, 2018