Neuroinfektioner

Abstract Background Aseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng. Methods We reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease. Results A total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region. Conclusions This study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.

by Charles M. Manyelo, Novel N. Chegou, James A. Seddon, Candice I. Snyders, Hygon Mutavhatsindi, Portia M. Manngo, Gerhard Walzl, Kim Stanley, Regan S. Solomons Introduction Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke. Methods We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants. Results After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity. Conclusion Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.

by Robert Deiss, Carolina V. Loreti, Ana G. Gutierrez, Eudoxia Filipe, Milton Tatia, Sheila Issufo, Iza Ciglenecki, Anne Loarec, Henriques Vivaldo, Carmen Barra, Carolina Siufi, Lucas Molfino, Natalia Tamayo Antabak Background Cryptococcal meningitis is a leading cause of HIV-related mortality in sub-Saharan Africa, however, screening for cryptococcal antigenemia has not been universally implemented. As a result, data concerning cryptococcal meningitis and antigenemia are sparse, and in Mozambique, the prevalence of both are unknown. Methods We performed a retrospective analysis of routinely collected data from a point-of-care cryptococcal antigen screening program at a public hospital in Maputo, Mozambique. HIV-positive patients admitted to the emergency department underwent CD4 count testing; those with pre-defined abnormal vital signs or CD4 count ≤ 200 cells/μL received cryptococcal antigen testing and lumbar punctures if indicated. Patients with CM were admitted to the hospital and treated with liposomal amphotericin B and flucytosine; their 12-week outcomes were ascertained through review of medical records or telephone contact by program staff made in the routine course of service delivery. Results Among 1,795 patients screened for cryptococcal antigenemia between March 2018—March 2019, 134 (7.5%) were positive. Of patients with cryptococcal antigenemia, 96 (71.6%) were diagnosed with CM, representing 5.4% of all screened patients. Treatment outcomes were available for 87 CM patients: 24 patients (27.6%) died during induction treatment and 63 (72.4%) survived until discharge; of these, 38 (60.3%) remained in care, 9 (14.3%) died, and 16 (25.3%) were lost-to follow-up at 12 weeks. Conclusions We found a high prevalence of cryptococcal antigenemia and meningitis among patients screened at an emergency department in Maputo, Mozambique. High mortality during and after induction therapy demonstrate missed opportunities for earlier detection of cryptococcal antigenemia, even as point-of-care screening and rapid assessment in an emergency room offer potential to improve outcomes.

Abstract Background The lack of background disease incidence rates in sub-Saharan countries where the RTS,S/AS01E malaria vaccine is being implemented may hamper the assessment of vaccine safety and effectiveness. This study aimed to document baseline incidence rates of meningitis, malaria, mortality, and other health outcomes prior to vaccine introduction through the Malaria Vaccine Implementation Programme. Methods An ongoing disease surveillance study is combining prospective cohort event monitoring and hospital-based disease surveillance in three study sites in Ghana and Kenya. An interim analysis was performed on the prospective cohort in which children were enrolled in two age-groups (the 5 to 17 months or 6 to 12 weeks age-group), capturing data in the framework of routine medical practice before the introduction of the malaria vaccine. Incidence and mortality rates were computed with 95% confidential intervals (CI) using an exact method for a Poisson variable. Results This analysis includes 14,329 children; 7248 (50.6%) in the 6 to 12 weeks age-group and 7081 (49.4%) in the 5 to 17 months age-group. In the 5 to 17 months age-group (where the malaria vaccine was planned to be subsequently rolled out) the meningitis, malaria, severe malaria and cerebral malaria incidences were 92 (95% CI 25–236), 47,824 (95% CI 45,411–50,333), 1919 (95% CI 1461–2476) and 33 (95% CI 1–181) per 100,000 person-years, respectively. The all-cause mortality was 969 (95% CI 699–1310) per 100,000 person-years. Conclusion Incidence estimates of multiple health outcomes are being generated to allow before-after vaccine introduction comparisons that will further characterize the benefit-risk profile of the RTS,S/AS01E vaccine. Trial registration: clinicaltrials.gov NCT02374450.

Abstract Background Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. Method This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7–1.0 mg/kg) and oral fluconazole (800 mg orally/day). Results Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. Conclusion Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

by John Njuma Libwea, Mark A. Fletcher, Paul Koki Ndombo, Angeline Boula, Nadesh Taku Ashukem, Madeleine Ngo Baleba, Rachel Sandrine Kingue Bebey, Eric Gaston Nkolo Mviena, Jean Tageube, Marie Kobela Mbollo, Sinata Koulla-Shiro, Shabir Madhi, Berthe-Marie Njanpop-Lafourcade, Ali Mohammad, Elizabeth Begier, Joanna Southern, Rohini Beavon, Bradford Gessner Background The 13-valent pneumococcal conjugate vaccine (PCV13) entered Cameroon’s childhood national immunization programme (NIP) in July 2011 under a 3-dose schedule (6, 10, 14 weeks of age) without any catch-up. We described the impact of PCV13 onserotype distribution among pneumococcal meningitis cases over time. Methods We used laboratory-based sentinel surveillance data to identify meningitis cases among 2- to 59-month-old children with clinically-suspected bacterial meningitis (CSBM) admitted to hospitals in Yaoundé (August 2011-December 2018). Purulent meningitis cases had a cerebrospinal fluid (CSF) white blood cell (WBC) count ≥20 per mm3. Pneumococcal meningitis cases had S. pneumoniae identified from CSF, with serotyping by polymerase chain reaction. Years 2011-2014 were described as early PCV13 era (EPE) and years 2015-2018 as late PCV13 era (LPE) impact periods. Results Among children hospitalized with CSBM who had a lumbar puncture obtained, there was no significant change from the EPE versus the LPE in the percentage identified with purulent meningitis: 7.5% (112/1486) versus 9.4% (154/1645), p = 0.0846. The percentage of pneumococcal meningitis cases due to PCV13 vaccine-serotype (VST) decreased from 62.0% (31/50) during the EPE to 35.8% (19/53) in the LPE, p = 0.0081. The most frequent pneumococcal meningitis VSTs during the EPE were 6A/6B (30%) and 5 (6%), and during the LPE were 14 (13.2%), 3 (7.6%), 4 (5.6%) and 18C (5.6%). Conclusion Four to seven years after PCV13 introduction, the proportion of pneumococcal meningitis due to vaccine serotypes has declined, mainly due to reductions of serotypes 6A/6B, 1, 19A, and 23F; nevertheless, PCV13 VSTs remain common. Because the analyzed surveillance system was not consistent or population based, we could not estimate incidence or overall impact; this emphasizes the need for improved surveillance to document further the utility of PCV13 immunization in Cameroon.

Journal of Medical Virology, Volume 93, Issue 6, Page 3389-3396, June 2021.

A. S. Jyotsna et al.

Introduction Individuals recruited into clinical trials for life-threatening illnesses are particularly vulnerable. This is especially true in low-income settings. The decision to enrol may be influenced by existing inequalities, poor healthcare infrastructure and fear of death. Where patients are confused or unconscious the responsibility for this decision falls to relatives. This qualitative study is nested in the ongoing AMBIsome Therapy Induction OptimisatioN (AMBITION) Trial. AMBITION is recruiting participants from five countries in sub-Saharan Africa and is trialling a novel treatment approach for HIV-associated cryptococcal meningitis, an infection known to affect brain function. We aim to learn from the experiences of participants, relatives and researchers involved in AMBITION. Methods and analysis We will collect data through in-depth interviews with trial participants and the next of kin of participants who were confused at enrolment and therefore provided surrogate consent. Data will be collected in Gaborone, Botswana; Kampala, Uganda and Harare, Zimbabwe. Interviews will follow a narrative approach including participatory drawing of participation timelines. This will be supplemented by direct observation of the research process at each of the three recruiting hospitals. Interviews will also take place with researchers from the African and European institutions that form the partnership through which the trial is administered. Interviews will be transcribed verbatim, translated (if necessary) and organised thematically for narrative analysis. Ethics and dissemination This study has been approved by the Health Research Development Committee, Gaborone (Reference: HPDME:13/18/1); Makerere School of Health Sciences Institutional Review Board, Kampala (Reference: 2019–061); University of Zimbabwe Joint Research Ethics Committee, Harare (Reference: 219/19), and the London School of Hygiene and Tropical Medicine (Reference: 17957). Study findings will be shared with research participants from the sites, key stakeholders at each research institution and ministries of health to help inform the development and implementation of future trials. The findings of this study will be published in journals and presented at academic meetings. Trial registration Registered at www.clinicaltrials.gov:NCT04296292.

Abstract Multidrug-resistant Pseudomonas aeruginosa has limited treatment options. Treatment of healthcare-associated meningitis requires agents active against the organism in vitro and able to penetrate the cerebrospinal fluid adequately. Ceftolozane-tazobactam has been recently approved to treat various Gram-negative organisms, including Pseudomonas aeruginosa; however, ceftolozane’s penetration into human cerebrospinal fluid is unknown. Here, we present a case of a patient with multidrug-resistant Pseudomonas aeruginosa meningitis treated with a continuous infusion of ceftolozane-tazobactam. Samples of both serum and cerebrospinal fluid were analyzed for ceftolozane concentration on continuous infusion. Cerebrospinal fluid concentrations of ceftolozane were 83% of that in serum. Treatment with ceftolozane-tazobactam, along with combinations of other antibiotics, resulted in clearance of organism from the patient’s cerebrospinal fluid and marked decrease in inflammatory cells. Studies are warranted to determine the efficacy of ceftolozane-tazobactam for patients with healthcare-associated meningitis.

by Olga Spekker, David R. Hunt, William Berthon, László Paja, Erika Molnár, György Pálfi, Michael Schultz Abnormally pronounced digital impressions (APDIs) on the endocranial surface develop secondary to a prolonged rise in the intracranial pressure. This can result from a number of pathological conditions, including hydrocephalus due to tuberculous meningitis (TBM). APDIs have been described with relation to TBM not only in the modern medical literature but also in several paleopathological studies. However, APDIs are not pathognomonic for TBM and their diagnostic value for identifying TBM in past human populations has not been evaluated in identified pre-antibiotic era skeletons. To assess the diagnostic value of APDIs for the first time, a macroscopic investigation was performed on skeletons from the Terry Collection (Smithsonian Institution, Washington, DC, USA). Our material consisted of 234 skeletons with tuberculosis (TB) as the cause of death (TB group) and 193 skeletons with non-tuberculous (NTB) causes of death (NTB group). The macroscopic examination focused on the stage of the prominence and frequency of APDIs in the TB group and NTB group. To determine the significance of difference (if any) in the frequency of APDIs between the two groups, χ2 testing of our data was conducted. We found that APDIs were twice as common in the TB group than in the NTB group. The χ2 comparison of the frequencies of APDIs revealed a statistically significant difference between the two groups. In addition, APDIs with more pronounced stages were recorded more frequently in the TB group. Our results indicate that APDIs can be considered as diagnostic criteria for TBM in the paleopathological practice. With suitable circumspection, their utilization provides paleopathologists with a stronger basis for identifying TB and consequently, with a more sensitive means of assessing TB frequency in past human populations.

Abstract Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

Lymphocytic choriomeningitis virus (LCMV) is an enveloped single-stranded RNA virus and a member of the family Arenaviridae, which includes highly pathogenic human viruses such as Lassa virus (LASV) and Junin virus (JUNV). Human transmission of arenaviruses usually occurs through direct contact with infected animals, particularly rodents, or by inhalation of airborne viruses through their excreta and other secretions. Although infections with LASV and JUNV are geographically limited by the habitations of their reservoir rodents (Mastomys natalensis and Calomys musculinus), LCMV circulate among the house mouse (Mus musculus), resulting in the global distribution of infection burden (Brisse and Ly, 2019).

Journal of Medical Virology, Volume 93, Issue 4, Page 1929-1931, April 2021.

Tropical Medicine & International Health, EarlyView.

AbstractCryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4–100) and 94.1% (88.3–98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2–99.6) and 99.3% (96.7–99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97–99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.

Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome.

To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.

To monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.

To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM).

The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome.

The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.

To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections.

Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.

Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings.

Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.

Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.

Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse.