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Antimicrobial Agents and Chemotherapy, Ahead of Print.

Strange are the opportunities that presented themselves and where the path led during the coronavirus disease 2019 (COVID-19) pandemic. It all began when I was at a National Institutes of Health (NIH) study section on 5–6 March 2020 in Washington, DC, expecting to fly to Boston for the Conference on Retroviruses and Opportunistic Infections (CROI) when a Friday email announced the cancellation of in-person attendance at the conference (wisely). I had been looking forward to CROI, having worked for weeks to get visa appointments for two Ugandan scientists to travel to CROI to present their cryptococcal meningitis abstracts. My team makes an effort always to present cryptococcal abstracts at CROI so that people do not forget that opportunistic infections still exist worldwide. In March 2020, we were excited to have just launched a phase 2 trial to test oral amphotericin B formulation for cryptococcal meningitis.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background Leptospirosis is a zoonotic disease that afflicts both humans and animals. It progresses from flu-like symptoms to more severe hepatic and renal failure, and may also lead to aseptic meningitis. Individuals with autoimmune diseases (ADs) are potentially more susceptible to Leptospirosis. Thus far, limited data has documented the association between Leptospirosis and autoimmune disorders. Case presentation The patient had a definitive pathological diagnosis of Sjögren’s syndrome (SS). Due to recurrent headaches, the patient sought consultation with a neurologist. Lumbar puncture revealed elevated white blood cells and protein levels in the cerebrospinal fluid, along with decreased glucose. Tuberculous meningitis was suspected. Radiographic imaging exhibited meningeal enhancement, ventricular enlargement, and hydrocephalus. The patient commenced treatment with anti-tuberculosis therapy and corticosteroids. Subsequently, high-throughput sequencing (HTS) of cerebrospinal fluid identified the presence of Leptospira interrogans. The patient was ultimately diagnosed with Leptospiral meningitis, and underwent antimicrobial and immunosuppressive therapy, resulting in stabilization of the condition and gradual symptom recovery. Conclusions The case highlights the challenges in diagnosing and managing leptospirosis-related meningitis in the presence of ADs and emphasizes the importance of utilizing HTS for accurate pathogen detection. The potential correlation between leptospirosis and SS warrants further investigation, as does the need for multidisciplinary involvement in treatment strategies for such complex cases. …

Abstract Background Leptospirosis is a zoonotic disease that afflicts both humans and animals. It progresses from flu-like symptoms to more severe hepatic and renal failure, and may also lead to aseptic meningitis. Individuals with autoimmune diseases (ADs) are potentially more susceptible to Leptospirosis. Thus far, limited data has documented the association between Leptospirosis and autoimmune disorders. Case presentation The patient had a definitive pathological diagnosis of Sjögren’s syndrome (SS). Due to recurrent headaches, the patient sought consultation with a neurologist. Lumbar puncture revealed elevated white blood cells and protein levels in the cerebrospinal fluid, along with decreased glucose. Tuberculous meningitis was suspected. Radiographic imaging exhibited meningeal enhancement, ventricular enlargement, and hydrocephalus. The patient commenced treatment with anti-tuberculosis therapy and corticosteroids. Subsequently, high-throughput sequencing (HTS) of cerebrospinal fluid identified the presence of Leptospira interrogans. The patient was ultimately diagnosed with Leptospiral meningitis, and underwent antimicrobial and immunosuppressive therapy, resulting in stabilization of the condition and gradual symptom recovery. Conclusions The case highlights the challenges in diagnosing and managing leptospirosis-related meningitis in the presence of ADs and emphasizes the importance of utilizing HTS for accurate pathogen detection. The potential correlation between leptospirosis and SS warrants further investigation, as does the need for multidisciplinary involvement in treatment strategies for such complex cases. …

Abstract Background Leptospirosis is a zoonotic disease that afflicts both humans and animals. It progresses from flu-like symptoms to more severe hepatic and renal failure, and may also lead to aseptic meningitis. Individuals with autoimmune diseases (ADs) are potentially more susceptible to Leptospirosis. Thus far, limited data has documented the association between Leptospirosis and autoimmune disorders. Case presentation The patient had a definitive pathological diagnosis of Sjögren’s syndrome (SS). Due to recurrent headaches, the patient sought consultation with a neurologist. Lumbar puncture revealed elevated white blood cells and protein levels in the cerebrospinal fluid, along with decreased glucose. Tuberculous meningitis was suspected. Radiographic imaging exhibited meningeal enhancement, ventricular enlargement, and hydrocephalus. The patient commenced treatment with anti-tuberculosis therapy and corticosteroids. Subsequently, high-throughput sequencing (HTS) of cerebrospinal fluid identified the presence of Leptospira interrogans. The patient was ultimately diagnosed with Leptospiral meningitis, and underwent antimicrobial and immunosuppressive therapy, resulting in stabilization of the condition and gradual symptom recovery. Conclusions The case highlights the challenges in diagnosing and managing leptospirosis-related meningitis in the presence of ADs and emphasizes the importance of utilizing HTS for accurate pathogen detection. The potential correlation between leptospirosis and SS warrants further investigation, as does the need for multidisciplinary involvement in treatment strategies for such complex cases. …

Abstract Purpose To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). Methods Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. Results Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27–43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31–514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). Conclusions Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up. …

Abstract Purpose To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). Methods Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. Results Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27–43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31–514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). Conclusions Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up. …

Abstract Background Hydrocephalus is a frequent complication of tuberculous meningitis (TBM), and ventriculoperitoneal shunt (VPS) has been shown to improve short-term prognosis for patients with TBM-associated hydrocephalus. However, questions remain about long-term prognosis and shunt-related complications. This study aims to provide a comprehensive assessment of both long-term prognosis and shunt-related complications in patients with TBM-induced hydrocephalus who have undergone VPS treatment. Methods This retrospective study analyzed the clinical data of TBM patients with hydrocephalus treated with VPS at Peking Union Medical College Hospital between December 1999 and February 2023. Both short-term outcomes at discharge and long-term outcomes during follow-up were examined. Prognosis and shunt-related complications were assessed using the modified Rankin Scale (mRS) and the Activity of Daily Living (ADL) score to evaluate neurological function and autonomic living ability, respectively. Results A total of 14 patients with TBM-associated hydrocephalus were included in this study. Of these, 92.9% (13/14) exhibited favorable short-term outcomes, while 57.1% (8/14) showed positive long-term outcomes. Initial results indicated 6 complete recoveries (CR), 7 partial recoveries (PR), and 1 treatment failure. No catheter-related complications were observed initially. Long-term results included 4 CRs, 4 PRs, and 6 treatment failures. A variety of shunt surgery-related complications were noted, including three instances of catheter obstruction, one of incision infection, one of catheter-related infection, one of acute cerebral infarction, and one of transient peritoneal irritation accompanied by diarrhea. Conclusions VPS appears to be an effective and well-tolerated treatment for TBM-associated hydrocephalus, efficiently alleviating acute intracranial hypertension. Nonetheless, continuous long-term monitoring and proactive management are essential to mitigate the risk of catheter-related complications. …

Abstract Background Few studies have analyzed the clinical characteristics and adverse factors affecting prognosis in older patients with tuberculous meningitis (TBM). This study aimed to compare the clinical characteristics of TBM in older patients with those in younger and middle-aged patients. Methods This single-center retrospective study extracted data on the clinical features, cerebrospinal fluid changes, laboratory results, imaging features, and outcomes of patients with TBM from patient medical records and compared the findings in older patients (aged 60 years and older) with those of younger and middle-aged patients (aged 18–59 years). Results The study included 197 patients with TBM, comprising 21 older patients aged 60–76 years at onset, and 176 younger and middle-aged patients aged 18–59 years at onset. Fever was common in both older (81%) and younger and middle-aged patients (79%). Compared with younger and middle-aged patients, older patients were more likely to have changes in awareness levels (67% vs. 40%), peripheral nerve dysfunction (57% vs. 29%), changes in cognitive function (48% vs. 20%), and focal seizures (33% vs. 6%), and less likely to have headache (71% vs. 93%), neck stiffness on meningeal stimulation (38% vs. 62%), and vomiting (47% vs. 68%). The Medical Research Council staging on admission of older patients was stage II (52%) and stage III (38%), whereas most younger and middle-aged patients had stage I (33%) and stage II (55%) disease. Neurological function evaluated on the 28th day of hospitalization was more likely to show poor prognosis in older patients than in younger and middle-aged patients (76% vs. 25%). Older patients had significantly higher red blood cell counts and blood glucose levels, and significantly lower serum albumin and sodium levels than those in younger and middle-aged patients. The cerebrospinal fluid protein levels, nucleated cell counts, glucose levels, and chloride levels did not differ significantly by age. Conclusion In patients with TBM, older patients have more severe clinical manifestations, a higher incidence of hydrocephalus and cerebral infarction, and longer hospital stays than younger and middle-aged patients. Older patients thus require special clinical attention. …

Abstract Background Few studies have analyzed the clinical characteristics and adverse factors affecting prognosis in older patients with tuberculous meningitis (TBM). This study aimed to compare the clinical characteristics of TBM in older patients with those in younger and middle-aged patients. Methods This single-center retrospective study extracted data on the clinical features, cerebrospinal fluid changes, laboratory results, imaging features, and outcomes of patients with TBM from patient medical records and compared the findings in older patients (aged 60 years and older) with those of younger and middle-aged patients (aged 18–59 years). Results The study included 197 patients with TBM, comprising 21 older patients aged 60–76 years at onset, and 176 younger and middle-aged patients aged 18–59 years at onset. Fever was common in both older (81%) and younger and middle-aged patients (79%). Compared with younger and middle-aged patients, older patients were more likely to have changes in awareness levels (67% vs. 40%), peripheral nerve dysfunction (57% vs. 29%), changes in cognitive function (48% vs. 20%), and focal seizures (33% vs. 6%), and less likely to have headache (71% vs. 93%), neck stiffness on meningeal stimulation (38% vs. 62%), and vomiting (47% vs. 68%). The Medical Research Council staging on admission of older patients was stage II (52%) and stage III (38%), whereas most younger and middle-aged patients had stage I (33%) and stage II (55%) disease. Neurological function evaluated on the 28th day of hospitalization was more likely to show poor prognosis in older patients than in younger and middle-aged patients (76% vs. 25%). Older patients had significantly higher red blood cell counts and blood glucose levels, and significantly lower serum albumin and sodium levels than those in younger and middle-aged patients. The cerebrospinal fluid protein levels, nucleated cell counts, glucose levels, and chloride levels did not differ significantly by age. Conclusion In patients with TBM, older patients have more severe clinical manifestations, a higher incidence of hydrocephalus and cerebral infarction, and longer hospital stays than younger and middle-aged patients. Older patients thus require special clinical attention. …

Abstract Background The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. Case presentation A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. Conclusion This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect. …

Abstract Background Bacteria account for nearly one third of the causes of community-acquired central nervous system infections, and traditional diagnostic methods are based on culture results, which are time-consuming and have a low detection rate leading to delayed diagnosis and treatment. Since metagenomic next-generation sequencing (mNGS) has the advantages of high timeliness and only detecting microbial trace gene fragments, it has been used more widely in recent years. Based on this, we explored whether the application of cerebrospinal fluid (CSF) mNGS is advantageous in patients with community-acquired purulent meningitis, especially in people who have already used antibiotics. Methods This was a retrospective study of 63 patients with community-acquired purulent meningitis admitted to the Department of Neurology of Shanxi Bethune Hospital from March 2018 to November 2022. Data were systematically collected and classified into CSF culture group, blood culture group and CSF mNGS group according to different detection methods, and the total detection rate of each method was calculated. Each group of patients was divided into two subgroups according to whether antibiotics were used before sampling. The detection rates of the three groups were compared within and between groups to explore whether mNGS has advantages over traditional methods and the influence of antibiotic use on detection rates of the three methods. Results Among the 63 patients, the cases of CSF culture, blood culture and CSF mNGS were 56, 46, 44, respectively. The total detection rates of the three methods were 17.86%, 36.96%, 81.82%, with statistical differences (p 

by Bilal Ahmad Rahim, Niamatullah Ishaq, Ghulam Mohayuddin Mudaser, Walter R. Taylor …

New England Journal of Medicine, Volume 389, Issue 15, Page 1357-1367, October 2023.

New England Journal of Medicine, Volume 389, Issue 15, Page 1425-1426, October 2023.

Abstract Background Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis. Methods Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel. Results A total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples. Conclusions The BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment. …

Abstract Background Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). Materials/methods This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. Results Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p  0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). Conclusions Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci. …

Abstract Background Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). Materials/methods This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. Results Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p  0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). Conclusions Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci. …

AbstractBackgroundLinezolid is evaluated in novel treatment regimens for tuberculous meningitis (TBM). Linezolid pharmacokinetics have not been characterized in this population, particularly in cerebrospinal fluid (CSF) where exposures may be affected by changes in protein concentration. Linezolid co-administration with high-dose rifampicin, has also not been studied. We aimed to characterize linezolid plasma and CSF pharmacokinetics in adults with TBM.MethodsIn LASER-TBM pharmacokinetic-substudy, the intervention groups received high-dose rifampicin (35mg/kg) plus linezolid 1200mg/day for 28days, then reduced to 600mg/day. Plasma sampling was done on day 3 (intensive) and on day 28 (sparse). A lumbar CSF sample was obtained on both visits.Results30-participants, median(min-max) age and weight of 40(27–56)years and 58(30–96)kg, contributed 247 plasma and 28 CSF observations. Plasma pharmacokinetics was described by one-compartment model with first-order absorption and saturable elimination. Maximal clearance was 7.25L/h, and Km was 27.2mg/L. Rifampicin co-treatment duration did not affect linezolid pharmacokinetics. CSF-Plasma partitioning correlated with CSF total-protein upto 1.2g/L where the partition-coefficient reached maximal value of 37%. Plasma-CSF equilibration half-life was ∼3.5hoursConclusionLinezolid was readily detected in CSF despite high-dose rifampicin co-administration. These findings support continued clinical evaluation of linezolid plus high-dose rifampicin for the treatment of TBM in adults.

IntroductionFebrile infants 90 days and younger are at risk of invasive bacterial infections (bacteraemia and meningitis) and urinary tract infections. Together this is previously termed serious bacterial infection with an incidence of approximately 10–20%. The National Institute for Health and Care Excellence guidance advocates a cautious approach with most infants requiring septic screening, parenteral broad-spectrum antibiotics and hospital admission. Internationally, variations exist in the approach to febrile infants, with European and North American guidance advocating a tailored approach based on clinical features and biomarker testing. None of the available international clinical decision aids (CDAs) has been validated in the UK and Irish cohorts. The aim of the Febrile Infant Diagnostic Assessment and Outcome (FIDO) Study is to prospectively validate a range of CDAs in a UK and Irish population including CDAs that use procalcitonin testing. Methods and analysisThe FIDO Study is a prospective multicentre mixed-methods cohort study conducted in UK and Irish hospitals. All infants aged 90 days and younger presenting with fever or history of fever (≥38°C) are eligible for inclusion. Infants will receive standard emergency clinical care without delay. Clinical data and blood samples will be collected, and consent will be obtained at the earliest appropriate opportunity using research without prior consent methodology. The performance and cost-effectiveness of CDAs will be assessed. An embedded qualitative study will explore clinician and caregiver views on different approaches to care and perceptions of risk. Ethics and disseminationThis study was reviewed and approved by the Office for Research Ethics Committees Northern Ireland-Health and Social Care Research Ethics Committee B, Public Benefit and Privacy Panel for Health and Social Care Scotland, and Children’s Health Ireland Research and Ethics Committee Ireland. The results of this study will be presented at academic conferences and in peer-reviewed publications. Trial registration numberNCT05259683. …

Abstract The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility—Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents. …

Abstract The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility—Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents. …

Bacterial meningitis is defined clinically by a triad that includes fever, neck stiffness and altered mental status and represents a medical emergency with a high mortality rate. Its worldwide incidence in high-income countries is estimated at 80/100,000 individuals per year. Delayed antimicrobial therapy increases mortality and neurological sequelae for survivors. Rapid diagnostic methods were developed to identify the most common pathogens responsible for community-acquired bacterial meningitis.

Purpose of review Congenital infections are a major cause of childhood multidomain neurodevelopmental disabilities. They contribute to a range of structural brain abnormalities that can cause severe neurodevelopmental impairment, cerebral palsy, epilepsy, and neurosensory impairments. New congenital infections and global viral pandemics have emerged, with some affecting the developing brain and causing neurodevelopmental concerns. This review aims to provide current understanding of fetal infections and their impact on neurodevelopment. Recent findings There are a growing list of congenital infections causing neurodevelopmental issues, including cytomegalovirus, Zika virus, syphilis, rubella, lymphocytic choriomeningitis virus, and toxoplasmosis. Fetal exposure to maternal SARS-CoV-2 may also pose risk to the developing brain and impact neurodevelopmental outcomes, although studies have conflicting results. As Zika virus was a recently identified congenital infection, there are several new reports on child neurodevelopment in the Caribbean and Central and South America. For many congenital infections, children with in-utero exposure, even if asymptomatic at birth, may have neurodevelopmental concerns manifest over time. Summary Congenital infections should be considered in the differential diagnosis of a child with neurodevelopmental impairments. Detailed pregnancy history, exposure risk, and testing should guide diagnosis and multidisciplinary evaluation. Children with congenital infections should have long-term follow-up to assess for neurodevelopmental delays and other neurosensory impairments. Children with confirmed delays or high-risk should be referred for rehabilitation therapies.

Objective: Cryptococcal meningitis (CM) is a leading cause of mortality in people living with HIV (PLHIV). Despite recommendation by the National programme, Cryptococcal Antigen (CrAg) screening in PLHIV with CD4 …

Abstract Purpose There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. Methods A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. Results The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p  100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). Conclusion Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making. …

Abstract Purpose There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. Methods A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. Results The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p  100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). Conclusion Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making. …

Tropical Medicine &International Health, EarlyView.

by Hui Wang, Yulu Fang, Yongtao Jia, Jiajie Tang, Changzheng Dong Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB, especially among children. Since the 21st century, EVB has been widely prevalent worldwide, and can cause serious diseases, such as viral meningitis, myocarditis, and neonatal sepsis. By using cryo-electron microscopy, the three-dimensional (3D) structures of EVB and their uncoating receptors (FcRn and CAR) have been determined, laying the foundation for the study of viral pathogenesis and therapeutic antibodies. A limited number of epitopes bound to neutralizing antibodies have also been determined. It is unclear whether additional epitopes are present or whether epitope mutations play a key role in molecular evolutionary history and epidemics, as in influenza and SARS-CoV-2. In the current study, the conformational epitopes of six representative EVB serotypes (E6, E11, E30, CVB1, CVB3 and CVB5) were systematically predicted by bioinformatics-based epitope prediction algorithm. We found that their epitopes were distributed into three clusters, where the VP1 BC loop, C-terminus and VP2 EF loop were the main regions of EVB epitopes. Among them, the VP1 BC loop and VP2 EF loop may be the key epitope regions that determined the use of the uncoating receptors. Further molecular evolution analysis based on the VP1 and genome sequences showed that the VP1 C-terminus and VP2 EF loop, as well as a potential “breathing epitope” VP1 N-terminus, were common mutation hotspot regions, suggesting that the emergence of evolutionary clades was driven by epitope mutations. Finally, footprints showed mutations were located on or near epitopes, while mutations on the receptor binding sites were rare. This suggested that EVB promotes viral epidemics by breaking the immune barrier through epitope mutations, but the mutations avoided the receptor binding sites. The bioinformatics study of EVB epitopes may provide important information for the monitoring and early warning of EVB epidemics and developing therapeutic antibodies.

AbstractBackgroundAmphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed.MethodsIn our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA).ResultsWe randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin.Grade 3–4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P = .05), particularly for anemia (21% vs 44%; P = .01) and potassium (5% vs 17%; P = .04).ConclusionsThis new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin.Clinical Trials RegistrationNCT04031833.

Abstract Background Ralstonia is a genus of Gram-negative opportunistic bacteria that can survive in many kinds of solutions and cause a variety of infections. Ralstonia spp. have increasingly been isolated and reported to cause infections in recent years, thanks to the development of identification methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and gene sequencing. However, infections caused by Ralstonia insidiosa are still rare. Only a few cases of respiratory infections and bloodstream infections have been reported, none of which involved meningitis. To the best of our knowledge, this is the first reported case of meningitis caused by R. insidiosa worldwide. It is necessary to report and review this case. Case presentation We report a case of meningitis caused by R. insidiosa following lumbar surgery in China. The patient exhibited symptoms of headache, dizziness, and recurrent fever. The fever remained unresolved after empiric antibiotic therapy with intravenous cefotaxime and vancomycin in the initial days. Cerebrospinal fluid (CSF) culture yielded Gram-negative non-fermentative bacteria, which were identified as R. insidiosa. As there was a lack of antibiotic susceptibility testing results, clinical pharmacists conducted a literature review to select appropriate antibiotics. The patient’s condition improved after receiving effective treatment with intravenous cefepime and levofloxacin. Conclusions Uncommon pathogens, such as R. insidiosa, should be considered in postoperative central nervous system (CNS) infections, particularly in cases with unsatisfactory results of empiric anti-infective therapy. This is the first reported case of meningitis caused by R. insidiosa worldwide. MALDI-TOF MS provides rapid and accurate identification of this pathogen. The antibiotic susceptibility testing results of R. indiosa may be interpreted based on the breakpoints for Pseudomonas spp., Burkholderia cepacia spp., and Acinetobacter spp. Our case presents a potential option for empiric therapy against this pathogen, at least in the local area. This is crucial to minimize the severity and mortality rates associated with meningitis. Standardized antibiotic susceptibility testing and breakpoints for the Ralstonia genus should be established in the future as cases accumulate. Cefepime and levofloxacin may be potential antibiotics for infections caused by R. indiosa. …

AbstractBackgroundCalcitonin gene-related peptide (CGRP), an immunomodulatory neuropeptide, is important for regulating pain transmission, vasodilation, and the inflammatory response. However, the molecular mechanisms of the CGRP-mediated immune response remain unknown.MethodsThe effects of CGRP on bacterial meningitis (BM) and the underlying mechanisms were investigated in BM mice in vivo and macrophages in vitro.ResultsPeripheral injection of CGRP-attenuated cytokine storms and protected mice from fatal pneumococcal meningitis, marked by increased bacterial clearance, improved neuroethology, and reduced mortality. When the underlying mechanisms were investigated, we found that CGRP induces proteasome-dependent degradation of MHC-II in macrophages and then inhibits CD4+ T cell activation. MARCH1 was identified as an E3 ligase that can be induced by CGRP engagement and promote K48-linked ubiquitination and degradation of MHC-II in macrophages. These results provide new insights into neuropeptide CGRP-mediated immune regulation mechanisms.ConclusionsTherefore, we conclude that targeting the nervous system and manipulating neuroimmune communication is a promising strategy for treating intracranial infections like bacterial meningitis.

AbstractHepatitis B Virus is a major driver of infectious disease mortality. Curative therapies are needed and ideally should induce CD8 T cell-mediated clearance of infected hepatocytes plus anti-surface antigen antibodies (anti-HBs) to neutralize residual virus. We developed a novel therapeutic vaccine using non-replicating arenavirus vectors. Antigens were screened for genotype conservation and magnitude and genotype reactivity of T cell response, then cloned into Pichinde virus vectors (rPICV, GS-2829) and lymphocytic choriomeningitis virus vectors (rLCMV, GS-6779). Alternating immunizations with rPICV and rLCMV induced high magnitude HBV T cell responses, with PICV vectors driving high anti-HBs titers. Dose schedule optimization in macaques achieved strong polyfunctional CD8 T cell responses with balanced specificity for core, HBsAg, and polymerase and high titer anti-HBs. In AAV-HBV mice, GS-2829 and GS-6779 were efficacious in animals with low pre-treatment serum HBsAg. Based on these results, GS-2829 and GS-6779 could become central components of cure regimens.

Dispatch - Lymphocytic Choriomeningitis Virus in Person Living with HIV, Connecticut, USA, 2021…

AbstractBackgroundPowassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp ticks, which has been associated with neuroinvasive disease and poor outcomes.MethodsA retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiological data of probable and confirmed neuroinvasive POWV cases.ResultsSixteen patients with neuroinvasive POWV were identified with a median age of 63.2 years and 62.5% were male. Six patients presented with rhombencephalitis, four with isolated meningitis, three with meningoencephalitis, two with meningoencephalomyelitis, and one with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Mortality within 90 days occurred in three cases (18.8%), and residual neurological deficits were seen in eight (72.7%) survivors.ConclusionsTo our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients that live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality among patients with neuroinvasive disease.

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 109 Issue: 2 Pages: 450-459 …

Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality.

BackgroundThe leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis. Methods and analysisThe AddaMAP trial is a phase II, open-label, Simon’s two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required. Ethics and disseminationThe study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal. Trial registration numberNCT03480191. …

Dispatch - Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism…

Abstract Background Predicting the short-term prognosis and severity of tuberculosis meningitis (TBM) patients without HIV infection can be challenging, and there have been no prior studies examining the neutrophil lymphocyte ratio (NLR) as a potential predictor of short-term prognosis or its relationship to TBM severity. We hypothesized that NLR might serve as an independent indicator of short-term prognostic significance and that there might be a correlation between NLR and severity. The aim of this study was to investigate the role of NLR as a predictor of short-term prognosis and its relationship to severity of tuberculosis meningitis patients without HIV infection. Methods We retrospectively collected data from patients diagnosed with TBM in the West China Hospital, Sichuan University, from the period between January 1st, 2018 and August 1st, 2019. Multivariable analysis was executed by the logistic regression model to verify the independence of the 28-day mortality, the discriminative power for predicting short-term prognosis was evaluated using a Receiver Operating Characteristic (ROC) curve, survival outcomes were analyzed using the Kaplan-Meier method and Pearson’s correlation analysis was performed to discuss correlation between NLR and the severity of TBM. Results We collected data from 231 TBM patients without HIV infection. 68 (29.4%) patients are classified as stage (I) 138(59.8%) patients are stage (II) 25(10.8%) patients are stage (III) 16(6.9%) patients died during the follow-up period of 28 days. By multiple logistic regression analyses, the NLR (OR = 1.065, 95% CI = 1.001–1.133, P = 0.045), peripheral neurological deficit (OR 7.335, 95% CI 1.964–27.385, P = 0 0.003) and hydrocephalus (OR 11.338, 95% CI 2.397–53.633, P = 0 0.002) are independent risk factors of 28-day mortality. The area under the ROC curve (AUC) for predicting short prognosis using NLR is 0.683 (95% CI 0.540–0.826, P = 0.015), the optimal cutoff value is 9.99(sensitivity: 56.3%, specificity: 80.9%). The Kaplan-Meier analysis demonstrated that patients with higher NLR(>9.99) had significantly worse survival outcomes(P

Abstract Background Predicting the short-term prognosis and severity of tuberculosis meningitis (TBM) patients without HIV infection can be challenging, and there have been no prior studies examining the neutrophil lymphocyte ratio (NLR) as a potential predictor of short-term prognosis or its relationship to TBM severity. We hypothesized that NLR might serve as an independent indicator of short-term prognostic significance and that there might be a correlation between NLR and severity. The aim of this study was to investigate the role of NLR as a predictor of short-term prognosis and its relationship to severity of tuberculosis meningitis patients without HIV infection. Methods We retrospectively collected data from patients diagnosed with TBM in the West China Hospital, Sichuan University, from the period between January 1st, 2018 and August 1st, 2019. Multivariable analysis was executed by the logistic regression model to verify the independence of the 28-day mortality, the discriminative power for predicting short-term prognosis was evaluated using a Receiver Operating Characteristic (ROC) curve, survival outcomes were analyzed using the Kaplan-Meier method and Pearson’s correlation analysis was performed to discuss correlation between NLR and the severity of TBM. Results We collected data from 231 TBM patients without HIV infection. 68 (29.4%) patients are classified as stage (I) 138(59.8%) patients are stage (II) 25(10.8%) patients are stage (III) 16(6.9%) patients died during the follow-up period of 28 days. By multiple logistic regression analyses, the NLR (OR = 1.065, 95% CI = 1.001–1.133, P = 0.045), peripheral neurological deficit (OR 7.335, 95% CI 1.964–27.385, P = 0 0.003) and hydrocephalus (OR 11.338, 95% CI 2.397–53.633, P = 0 0.002) are independent risk factors of 28-day mortality. The area under the ROC curve (AUC) for predicting short prognosis using NLR is 0.683 (95% CI 0.540–0.826, P = 0.015), the optimal cutoff value is 9.99(sensitivity: 56.3%, specificity: 80.9%). The Kaplan-Meier analysis demonstrated that patients with higher NLR(>9.99) had significantly worse survival outcomes(P

by Stephen Mac, Gerald Evans, Eleanor Pullenayegum, Samir N. Patel, Beate Sander Background The objective of this study was to estimate the economic burden attributable to laboratory-confirmed Lyme disease (LD) in Ontario, Canada and assess health outcomes associated with LD. Method We conducted a cohort study using laboratory-confirmed LD cases accrued between 2006 and 2018. The exposed cohort was matched 1:3 to the unexposed cohort using a combination of hard and propensity score matching. We used phase-of-care costing methods to calculate attributable costs for four phases of illness: pre-diagnosis, acute care, post-acute care, and continuing care in 2018 Canadian dollars. We used ICD-10-CA and OHIP billing codes to identify emergency department visits, physician billings and hospitalizations related to LD sequelae to assess health outcomes. Results A total of 2,808 cases were identified with a mean age of 46.5 (20.7) years and 44% female. Within 30-days, 404 (14.3%) cases required an ED visit and 63 (2.4%) cases required hospitalization. The mean (95% CI) total costs for LD cases in pre-diagnosis, acute, and post-acute care phases were $209 ($181, 238), $1,084 ($956, $1,212), and $1,714 ($1,499, $1,927), respectively. The highest mean attributable 10-day cost was $275 ($231, $319) during acute care. At 1-year post-infection, LD increased the relative risk of nerve palsies by 62 (20, 197), and polyneuropathy by 24 (3.0, 190). LD resulted in 16 Lyme meningitis events vs. 0 events in the unexposed. Conclusion Individuals with laboratory-confirmed LD have increased healthcare resource use pre-diagnosis and up to six months post-diagnosis, and were more likely to seek healthcare services related to LD sequelae. …

ObjectivesTo describe the implementation of screening for cryptococcal antigenaemia by point-of-care (POC) serum cryptococcal antigen (CrAg) lateral flow assay, measure the prevalence and factors associated with serum cryptococcal antigenaemia in the routine programmatic setting. DesignCross-sectional study. SettingSeventeen publicly funded antiretroviral therapy (ART) centres in Mumbai, India. ParticipantsSerum CrAg screening was offered to all adolescents (>10 years of age) and adults with advanced HIV disease (AHD) (CD4

Abstract Cryptococcal meningoencephalitis can occur in both previously healthy and immunocompromised hosts. Here, we describe a 55 year-old HIV-negative male with no known prior medical problems, who presented with three months of worsening headaches, confusion, and memory changes without fever. Magnetic resonance imaging of the brain demonstrated bilateral enlargement/enhancement of the choroid plexi, with hydrocephalus, temporal and occipital horn entrapments, as well as marked periventricular transependymal cerebrospinal fluid (CSF) seepage. CSF analysis yielded a lymphocytic pleocytosis and cryptococcal antigen titer of 1:160 but sterile fungal cultures. Despite standard antifungal therapy and CSF drainage, the patient had worsening confusion and persistently elevated intracranial pressures. External ventricular drainage led to improved mental status but only with valve settings at negative values. Ventriculoperitoneal shunt placement could thus not be considered due to a requirement for drainage into the positive pressure venous system. Due to this persistent CSF inflammation and cerebral circulation obstruction, the patient required transfer to the National Institute of Health. He was treated for cryptococcal post-infectious inflammatory response syndrome with pulse-taper corticosteroid therapy, with resultant reductions in CSF pressures along with decreased protein and obstructive material, allowing successful shunt placement. After tapering of corticosteroids, the patient recovered without sequelae. This case highlights (1) the necessity to consider cryptococcal meningitis as a rare cause of neurological deterioration in the absence of fever even in apparently immunocompetent individuals and (2) the potential for obstructive phenomena from inflammatory sequelae and the prompt response to corticosteroid therapy. …

Abstract Cryptococcal meningoencephalitis can occur in both previously healthy and immunocompromised hosts. Here, we describe a 55 year-old HIV-negative male with no known prior medical problems, who presented with three months of worsening headaches, confusion, and memory changes without fever. Magnetic resonance imaging of the brain demonstrated bilateral enlargement/enhancement of the choroid plexi, with hydrocephalus, temporal and occipital horn entrapments, as well as marked periventricular transependymal cerebrospinal fluid (CSF) seepage. CSF analysis yielded a lymphocytic pleocytosis and cryptococcal antigen titer of 1:160 but sterile fungal cultures. Despite standard antifungal therapy and CSF drainage, the patient had worsening confusion and persistently elevated intracranial pressures. External ventricular drainage led to improved mental status but only with valve settings at negative values. Ventriculoperitoneal shunt placement could thus not be considered due to a requirement for drainage into the positive pressure venous system. Due to this persistent CSF inflammation and cerebral circulation obstruction, the patient required transfer to the National Institute of Health. He was treated for cryptococcal post-infectious inflammatory response syndrome with pulse-taper corticosteroid therapy, with resultant reductions in CSF pressures along with decreased protein and obstructive material, allowing successful shunt placement. After tapering of corticosteroids, the patient recovered without sequelae. This case highlights (1) the necessity to consider cryptococcal meningitis as a rare cause of neurological deterioration in the absence of fever even in apparently immunocompetent individuals and (2) the potential for obstructive phenomena from inflammatory sequelae and the prompt response to corticosteroid therapy. …

Abstract Background Acute encephalitis syndrome (AES) differs in its spatio-temporal distribution in Vietnam with the highest incidence seen during the summer months in the northern provinces. AES has multiple aetiologies, and the cause remains unknown in many cases. While vector-borne disease such as Japanese encephalitis and dengue virus and non-vector-borne diseases such as influenza and enterovirus show evidence of seasonality, associations with climate variables and the spatio-temporal distribution in Vietnam differs between these. The aim of this study was therefore to understand the spatio-temporal distribution of, and risk factors for AES in Vietnam to help hypothesise the aetiology. Methods The number of monthly cases per province for AES, meningitis and diseases including dengue fever; influenza-like-illness (ILI); hand, foot, and mouth disease (HFMD); and Streptococcus suis were obtained from the General Department for Preventive Medicine (GDPM) from 1998–2016. Covariates including climate, normalized difference vegetation index (NDVI), elevation, the number of pigs, socio-demographics, JEV vaccination coverage and the number of hospitals were also collected. Spatio-temporal multivariable mixed-effects negative binomial Bayesian models with an outcome of the number of cases of AES, a combination of the covariates and harmonic terms to determine the magnitude of seasonality were developed. Results The national monthly incidence of AES declined by 63.3% over the study period. However, incidence increased in some provinces, particularly in the Northwest region. In northern Vietnam, the incidence peaked in the summer months in contrast to the southern provinces where incidence remained relatively constant throughout the year. The incidence of meningitis, ILI and S. suis infection; temperature, relative humidity with no lag, NDVI at a lag of one month, and the number of pigs per 100,000 population were positively associated with the number of cases of AES in all models in which these covariates were included. Conclusions The positive correlation of AES with temperature and humidity suggest that a number of cases may be due to vector-borne diseases, suggesting a need to focus on vaccination campaigns. However, further surveillance and research are recommended to investigate other possible aetiologies such as S. suis or Orientia tsutsugamushi. …

Abstract Background Klebsiella pneumoniae can infect a variety of sites, with the risk of infection being higher in the immunocompromised state such as diabetes mellitus. A distinct invasive syndrome has been detected mostly in Southeast Asia in the past two decades. A common destructive complication is pyogenic liver abscess that can be complicated by metastatic endophthalmitis as well as the involvement of the central nervous system, causing purulent meningitis or brain abscess. Case presentation We report a rare case of an invasive liver abscess caused by K. pneumoniae, with metastatic infections of meninges. A 68-year-old man with type 2 diabetes mellitus presented to our emergency department as sepsis. Sudden disturbed consciousness was noticed with presentation of acute hemiplegia and gaze preference mimicking a cerebrovascular accident. Conclusions The above case adds to the scarce literature on K. pneumoniae invasive syndrome with liver abscess and purulent meningitis. K. pneumoniae is a rare cause of meningitis and should raise suspicions about the disease in febrile individuals. In particular, Asian patients with diabetes presenting with sepsis and hemiplegia prompt a more thorough evaluation with aggressive treatment. …

A man near 60-year-old suddenly became unconscious; his right side was twitching, and he was staring in one direction, but this was relieved within ∼5 minutes with a tongue bite. Glasgow coma scale was 10. The patient had conjunctival congestion in both eyes for >20 days before admission. After the seizure, the patient had a headache, dizziness, apparent rotation, cough, nausea, and vomiting; he could not walk stably and easily toppled to the right when standing; and he had a low fever in the afternoon with body temperature fluctuating below 38°C but no obvious weight loss.

Abstract Background Acute encephalitis syndrome (AES) differs in its spatio-temporal distribution in Vietnam with the highest incidence seen during the summer months in the northern provinces. AES has multiple aetiologies, and the cause remains unknown in many cases. While vector-borne disease such as Japanese encephalitis and dengue virus and non-vector-borne diseases such as influenza and enterovirus show evidence of seasonality, associations with climate variables and the spatio-temporal distribution in Vietnam differs between these. The aim of this study was therefore to understand the spatio-temporal distribution of, and risk factors for AES in Vietnam to help hypothesise the aetiology. Methods The number of monthly cases per province for AES, meningitis and diseases including dengue fever; influenza-like-illness (ILI); hand, foot, and mouth disease (HFMD); and Streptococcus suis were obtained from the General Department for Preventive Medicine (GDPM) from 1998–2016. Covariates including climate, normalized difference vegetation index (NDVI), elevation, the number of pigs, socio-demographics, JEV vaccination coverage and the number of hospitals were also collected. Spatio-temporal multivariable mixed-effects negative binomial Bayesian models with an outcome of the number of cases of AES, a combination of the covariates and harmonic terms to determine the magnitude of seasonality were developed. Results The national monthly incidence of AES declined by 63.3% over the study period. However, incidence increased in some provinces, particularly in the Northwest region. In northern Vietnam, the incidence peaked in the summer months in contrast to the southern provinces where incidence remained relatively constant throughout the year. The incidence of meningitis, ILI and S. suis infection; temperature, relative humidity with no lag, NDVI at a lag of one month, and the number of pigs per 100,000 population were positively associated with the number of cases of AES in all models in which these covariates were included. Conclusions The positive correlation of AES with temperature and humidity suggest that a number of cases may be due to vector-borne diseases, suggesting a need to focus on vaccination campaigns. However, further surveillance and research are recommended to investigate other possible aetiologies such as S. suis or Orientia tsutsugamushi. …