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Before the advent of anti-tuberculosis drugs in the 1940’s, tuberculous meningitis (TBM) was a much feared and almost universally fatal form of tuberculosis. Thus when the first anti-tuberculosis drugs, streptomycin and para-aminosalycilic acid (PAS), became available, they were given first to those with TBM. Suddenly, the disease became treatable. Case-fatality fell from 70% with streptomycin and PAS, to around 30% with the combination of isoniazid, pyrazinamide and rifampicin[1].

fHbp is a virulence factor expressed by the human-specific pathogen N. meningitidis, a leading cause of meningitis and sepsis worldwide which frequently asymptomatically colonizes the human upper airway. fHbp binds human CFH, a negative regulator of the complement system, and has multiple roles during meningococcal infection. fHbp was initially identified as a vaccine antigen, named GNA1870 [1] or LP2086 [2]. It was then shown that the meningococcus binds CFH to its surface via an ~33 kDa protein, promoting bacterial survival in serum [3].

AbstractBackgroundLaboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed.MethodsThis observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without HIV and to evaluate their diagnostic performance in neurosyphilis compared with CSF.ResultsSerum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cut-off levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms’ sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively.ConclusionTo avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

Journal of Medical Virology, Accepted Article.

AbstractCoccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles necessitating evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis.

Abstract Background Tick-borne encephalitis (TBE), a viral infectious disease affecting the central nervous system, potentially resulting in prolonged neurological symptoms and other long-term sequelae. Case identification can be challenging as TBE can be associated with non-specific symptoms, and even in cases consistent with typical TBE symptoms, the rate of laboratory testing to confirm cases is unknown. This study assessed real-world TBE laboratory testing rates across Germany. Methods In this retrospective cross-sectional study, physicians provided data on TBE decision-making, laboratory testing (serological), and diagnostics behavior via in-depth qualitative interviews (N = 12) or a web-based quantitative survey of their patient medical records (N = 166). Hospital-based physicians who specialized in infectious disease, intensive care unit, emergency room, neurology, or pediatrics with experience managing and ordering testing for patients with meningitis, encephalitis, or non-specific central nervous system symptoms in the past 12 months were included. Data were summarized via descriptive statistics. TBE testing and positivity rates were assessed for the aggregate sample of 1400 patient charts and reported by presenting symptoms, region, and tick bite exposure. Results TBE testing rates ranged from 54.0% (non-specific neurological symptoms only) to 65.6% (encephalitis symptoms only); the percentage of TBE positive results ranged from 5.3% (non-specific neurological symptoms only) to 36.9% (meningitis symptoms only). TBE testing rates were higher among those with a tick bite history and/or who presented with headache, high fever, or flu-like symptoms. Conclusions The findings of this study suggest that patients with typical TBE symptoms are likely under-tested, thus likely leading to under-diagnosis in Germany. To ensure appropriate case identification, TBE testing should be consistently integrated into routine practice for all patients who present with relevant symptoms or exposure to common risk factors. …

Abstract Background Tick-borne encephalitis (TBE), a viral infectious disease affecting the central nervous system, potentially resulting in prolonged neurological symptoms and other long-term sequelae. Case identification can be challenging as TBE can be associated with non-specific symptoms, and even in cases consistent with typical TBE symptoms, the rate of laboratory testing to confirm cases is unknown. This study assessed real-world TBE laboratory testing rates across Germany. Methods In this retrospective cross-sectional study, physicians provided data on TBE decision-making, laboratory testing (serological), and diagnostics behavior via in-depth qualitative interviews (N = 12) or a web-based quantitative survey of their patient medical records (N = 166). Hospital-based physicians who specialized in infectious disease, intensive care unit, emergency room, neurology, or pediatrics with experience managing and ordering testing for patients with meningitis, encephalitis, or non-specific central nervous system symptoms in the past 12 months were included. Data were summarized via descriptive statistics. TBE testing and positivity rates were assessed for the aggregate sample of 1400 patient charts and reported by presenting symptoms, region, and tick bite exposure. Results TBE testing rates ranged from 54.0% (non-specific neurological symptoms only) to 65.6% (encephalitis symptoms only); the percentage of TBE positive results ranged from 5.3% (non-specific neurological symptoms only) to 36.9% (meningitis symptoms only). TBE testing rates were higher among those with a tick bite history and/or who presented with headache, high fever, or flu-like symptoms. Conclusions The findings of this study suggest that patients with typical TBE symptoms are likely under-tested, thus likely leading to under-diagnosis in Germany. To ensure appropriate case identification, TBE testing should be consistently integrated into routine practice for all patients who present with relevant symptoms or exposure to common risk factors. …

Abstract Background Anopheles farauti is one of the major vectors of malaria in the Southwest Pacific region and is responsible for past outbreaks in Australia. With an adaptable biting profile conducive to behavioural resistance to indoor residual spraying (IRS) and insecticide-treated nets (ITNs), its all-night biting behaviour can switch to biting mostly in the early evening. With limited insight into the biting profile of An. farauti populations in areas that have not encountered IRS or ITNs, the aim of this study was to develop insights on the biting behaviour of a malaria control naive population of An. farauti. Methods Biting profiles of An. farauti were conducted at Cowley Beach Training Area, in north Queensland, Australia. Initially, encephalitis virus surveillance (EVS) traps were used to document the 24-h biting profile of An. farauti and then human landing collections (HLC) were used to follow the 18.00–06.00 h biting profile. The human landing catches (HLC) were performed at both the end of the wet (April) and dry (October) seasons. Results Data exploration using a Random Forest Model shows that time of night is the most important variable for predicting An. farauti biting activity. Temperature was found to be the next important predictor, followed by humidity, trip, collector, and season. The significant effect of time of night and peak in time of night biting, between 19.00 and 20.00 h was also observed in a generalized linear model. The main effect of temperature was significant and non-linear and appears to have a positive effect on biting activity. The effect of humidity is also significant but its relationship with biting activity is more complex. This population’s biting profile is similar to populations found in other parts of its range prior to insecticide intervention. A tight timing for the onset of biting was identified with more variation with the end of biting, which is likely underpinned by an endogenous circadian clock rather than any light intensity. Conclusion This study sees the first record of a relationship between biting activity and the decreasing temperature during the night for the malaria vector, Anopheles farauti. …

cryptococcal meningitisCryptococcusHIV therapy…

AbstractBackgroundRandomized trials (RCTs) from low- and middle-income settings suggested early initiation of antiretroviral therapy (ART) leads to higher mortality among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about impact of ART timing on mortality in similar people in high-income settings.MethodsData on ART-naïve PWH diagnosed with CM from 1994-2012 from Europe/North America were pooled from the COHERE, NA-ACCORD and CNICS HIV cohort collaborations. Follow-up was considered from the date of CM diagnosis to earliest of the following: death, last follow-up or 6 months. We used marginal structural models to mimic an RCT comparing effects of early (within 14 days of CM) with late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders.ResultsOf 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, median age was 38 years (interquartile range 33-44); CD4 count was 19 cells/mm3 (10-56); and HIV viral load was 5.3 log10 copies/mL (4.9-5.6). Most participants (157, 83%) were males and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants following early ART regimen and 20 deaths among those following late ART regimen. Crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% CI: 0.64, 2.56) and 1.40 (0.66, 2.95).ConclusionsWe found little evidence that early ART was associated with higher mortality among PWH presenting with CM in high income settings, although confidence intervals were wide.

From the spring of 1920 until recently, there have been comparatively few new cases of epidemic (lethargic) encephalitis in North America, and interest in it has been kept up mainly by the surprising array of its somatic and psychic sequels. Within the last few weeks, however, reports have come of a large epidemic in Winnipeg, and smaller ones in Connecticut and elsewhere. Since 1917, nearly 2,000 articles on this disease have appeared, and, within the last two years, four comprehensive reviews in book form. In addition, the French investigator Levaditi has written a book giving a comparative epidemiologic, pathologic and clinical study of the three closely related acute infectious disorders of the nervous system: encephalitis, poliomyelitis and herpes.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Human cases of TBDs in Europe have increased steadily over the past decades [1]. Well-known pathogens such as Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV) have expanded their distribution, while several others, such as Borrelia miyamotoi, have only recently been identified as human pathogens [2–4]. Although this upsurge can in part be explained by improved medical diagnostics and awareness, human demographics, and human behavior, it is also a consequence of environmental and climatic changes [5–7].

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 108 Issue: 3 Pages: 477-481 …

Abstract Background Brain abscesses (BA) are severe lesions in the course of infective endocarditis (IE). We compare the bacteriological, clinical data, background, associated lesions, and outcome of IE patients with and without BAs, and assess the MRI characteristics of BAs. Methods Retrospective study of 351 consecutive patients with definite IE (2005–2020) and at least one brain MRI. Patients with and without BAs were compared. Results Twenty patients (5.7%) had BA (80% men; median age: 44.9 ± 11.5). They were younger (p = 0.035) and had a higher rate of predisposing factors (previous IE 20% vs 2.2%, p = 0.03), intravenous drug use [25% vs 2.2%; p < 0.0001]), underlying conditions (HIV infection, 20% vs 2.2%, p < 0.0001; alcohol abuse, 20% vs 2.2% p < 0.0001]; liver disease p = 0.04; hemodialysis, p = 0.001; type 2 diabetes, p = 0.001), bacterial meningitis (p = 0.0029), rare species involvement (35% vs 7%, p < 0.0006) and extra-cerebral abscesses (p = 0.0001) compared to patients without BA. Valve vegetations were larger in Group 1 (p = 0.046). Clinical presentation could suggest the diagnosis of BA in only 7/20 (35%) patients. MR identified 58 BAs (mean/patient 2.9; range 2–12): often multiple (80%), bilateral (55%) and ≤ 10 mm (72%). The presence of BA did not modify cardiac surgery indication and timing. Favorable outcome was observed in 85% of patients. Conclusion Rates of predisposing, underlying conditions, rare IE agents, meningitis and metastatic abscesses are significantly higher in BA-IE patients. As BAs can develop in asymptomatic IE patients, the impact of brain MRI on their management needs thoroughly to be further investigated. …

Abstract Background Brain abscesses (BA) are severe lesions in the course of infective endocarditis (IE). We compare the bacteriological, clinical data, background, associated lesions, and outcome of IE patients with and without BAs, and assess the MRI characteristics of BAs. Methods Retrospective study of 351 consecutive patients with definite IE (2005–2020) and at least one brain MRI. Patients with and without BAs were compared. Results Twenty patients (5.7%) had BA (80% men; median age: 44.9 ± 11.5). They were younger (p = 0.035) and had a higher rate of predisposing factors (previous IE 20% vs 2.2%, p = 0.03), intravenous drug use [25% vs 2.2%; p < 0.0001]), underlying conditions (HIV infection, 20% vs 2.2%, p < 0.0001; alcohol abuse, 20% vs 2.2% p < 0.0001]; liver disease p = 0.04; hemodialysis, p = 0.001; type 2 diabetes, p = 0.001), bacterial meningitis (p = 0.0029), rare species involvement (35% vs 7%, p < 0.0006) and extra-cerebral abscesses (p = 0.0001) compared to patients without BA. Valve vegetations were larger in Group 1 (p = 0.046). Clinical presentation could suggest the diagnosis of BA in only 7/20 (35%) patients. MR identified 58 BAs (mean/patient 2.9; range 2–12): often multiple (80%), bilateral (55%) and ≤ 10 mm (72%). The presence of BA did not modify cardiac surgery indication and timing. Favorable outcome was observed in 85% of patients. Conclusion Rates of predisposing, underlying conditions, rare IE agents, meningitis and metastatic abscesses are significantly higher in BA-IE patients. As BAs can develop in asymptomatic IE patients, the impact of brain MRI on their management needs thoroughly to be further investigated. …

Abstract Background Disseminated nocardiosis is a very rare disease. By now only few cases of meningitis and spondylodiscitis have been reported. To our knowledge, this is the first case of meningitis caused by Nocardia nova. Case presentation We report on a case of bacteraemia, meningitis and spondylodiscitis caused by N. nova in an immunocompetent patient. We describe the long, difficult path to diagnosis, which took two months, including all diagnostic pitfalls. After nocardiosis was diagnosed, intravenous antibiotic therapy with ceftriaxone, later switched to imipenem/cilastatin and amikacin, led to rapid clinical improvement. Intravenous therapy was followed by oral consolidation with co-trimoxazole for 9 months without any relapse within 4 years. Conclusions Establishing a diagnosis of nocardiosis is a precondition for successful antibiotic therapy. This requires close communication between clinicians and laboratory staff about the suspicion of nocardiosis, than leading to prolonged cultures and specific laboratory methods, e.g. identification by 16S rDNA PCR. …

Abstract This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (β), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high–high clusters), α, β, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV’s distribution in Gansu Province are needed.…

Abstract Background Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources. Methods The three data sources: RHIS, Child PIP, and DN Surveillance are integrated and linked by the Western Cape Provincial Health Data Centre using a unique patient identifier. We calculated the deduplicated total number of infectious disease deaths and estimated admission mortality rates using all three data sources. We determined the completeness of Child PIP and DN Surveillance in identifying deaths recorded in RHIS and the level of agreement for causes of death between data sources. Results Completeness of recorded in-facility infectious disease deaths in Child PIP (23/05/2007–08/02/2021) and DN Surveillance (2010–2013) was 70% and 69% respectively. The greatest agreement in infectious causes of death were for diarrhoea and LRTI: 92% and 84% respectively between RHIS and Child PIP, and 98% and 83% respectively between RHIS and DN Surveillance. In-facility infectious disease admission mortality rates decreased significantly for the province: 1.60 (95% CI: 1.37–1.85) to 0.73 (95% CI: 0.56–0.93) deaths per 1000 live births from 2007 to 2020. Conclusion RHIS had accurate causes of death amongst children dying from infectious diseases, particularly for diarrhoea and LRTI, with declining in-facility admission mortality rates over time. We recommend integrating data sources to ensure the most accurate assessment of child deaths. …

Abstract Background The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation. …

Journal of Medical Virology, Accepted Article.

AbstractBackgroundThe purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes.MethodsIndependent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with TNF concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality.ResultsMUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF(p = 1.8*10−8) and IFNγ(p = 2.3*10−6). In an additive genetic model, rs28737416 T/T genotype was associated with higher susceptibility to TBM (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.03, 1.49; p = 0.02), but not pulmonary tuberculosis (OR 1.11, 95% CI 0.98, 1.25; p = 0.10). TBM mortality was higher among participants with the rs28737416 T/T and T/C genotypes (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank p = 0.005) in a Vietnam discovery cohort (N = 210), an independent Vietnam validation cohort (N = 87; 9/87, 19.1% vs 1/20, 2.5%; log-rank p = 0.02), and an Indonesia validation cohort (N = 468, 127/287, 44.3% vs 65/181, 35.9%, log-rank p = 0.06).ConclusionsMUC5AC variants may contribute to immune changes that influence TBM outcomes.

AbstractBackgroundCryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with HIV(PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally.MethodsThis retrospective cohort study investigated CM incidence and all-cause mortality after CM diagnosis in PWH in the IeDEA cohort from 1996-2017. We estimated overall and region-specific incidence and incidence rate ratios using quasi-Poisson models adjusted for sex, age, calendar year, time-updated CD4, and time-updated antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities.ResultsAmong 518,852 PWH, there were 3,857 diagnosed cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. 2,478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (HR 1.31 for 50 vs 35 years; 95%CI 1.12-1.53), lower CD4 (HR 1.15 for 200 vs 350 cells/mm3; 95%CI 1.03-1.30), and earlier year of CM diagnosis (HR 0.51 for 2015 vs 2000; 95%CI 0.37-0.70) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine.ConclusionsMortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation. …

Abstract Background Disseminated nocardiosis is a very rare disease. By now only few cases of meningitis and spondylodiscitis have been reported. To our knowledge, this is the first case of meningitis caused by Nocardia nova. Case presentation We report on a case of bacteraemia, meningitis and spondylodiscitis caused by N. nova in an immunocompetent patient. We describe the long, difficult path to diagnosis, which took two months, including all diagnostic pitfalls. After nocardiosis was diagnosed, intravenous antibiotic therapy with ceftriaxone, later switched to imipenem/cilastatin and amikacin, led to rapid clinical improvement. Intravenous therapy was followed by oral consolidation with co-trimoxazole for 9 months without any relapse within 4 years. Conclusions Establishing a diagnosis of nocardiosis is a precondition for successful antibiotic therapy. This requires close communication between clinicians and laboratory staff about the suspicion of nocardiosis, than leading to prolonged cultures and specific laboratory methods, e.g. identification by 16S rDNA PCR. …

Abstract This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (β), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high–high clusters), α, β, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV’s distribution in Gansu Province are needed.…

Abstract Background Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources. Methods The three data sources: RHIS, Child PIP, and DN Surveillance are integrated and linked by the Western Cape Provincial Health Data Centre using a unique patient identifier. We calculated the deduplicated total number of infectious disease deaths and estimated admission mortality rates using all three data sources. We determined the completeness of Child PIP and DN Surveillance in identifying deaths recorded in RHIS and the level of agreement for causes of death between data sources. Results Completeness of recorded in-facility infectious disease deaths in Child PIP (23/05/2007–08/02/2021) and DN Surveillance (2010–2013) was 70% and 69% respectively. The greatest agreement in infectious causes of death were for diarrhoea and LRTI: 92% and 84% respectively between RHIS and Child PIP, and 98% and 83% respectively between RHIS and DN Surveillance. In-facility infectious disease admission mortality rates decreased significantly for the province: 1.60 (95% CI: 1.37–1.85) to 0.73 (95% CI: 0.56–0.93) deaths per 1000 live births from 2007 to 2020. Conclusion RHIS had accurate causes of death amongst children dying from infectious diseases, particularly for diarrhoea and LRTI, with declining in-facility admission mortality rates over time. We recommend integrating data sources to ensure the most accurate assessment of child deaths. …