Nyt fra tidsskrifterne

Abstract Aim Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. Methods Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. Results A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. Conclusions In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM. …

AbstractIntroductionPatients without HIV infection are increasingly recognised to be at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete.MethodsWe conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV, and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included.ResultsOf 475 patients with cryptococcosis, 90% were HIV-negative (426/475) with the marked predominance of HIV-negative cases evident in both Cryptococcus neoformans (88.7%) and C. gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n=91), organ transplantation (n=81), other immunocompromising condition (n=97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70/426). The serum cryptococcal antigen test was positive in 85.1 % of tested patients (319/375); high titres independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titre and/or fungaemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (p=0.89).ConclusionThe present study revealed 90% of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii cases, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

This study reports an epidemiological assessment of laboratory-confirmed group A streptococcal meningitis cases in the Netherlands using more than 40 years of national bacteriological surveillance data.

Abstract Background Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system that can cause significant morbidity and mortality. Although several prognostic factors have been identified, their clinical efficacy and use in combination to predict outcomes in immunocompetent patients with CM are not clear. Therefore, we aimed to determine the utility of those prognostic factors alone or in combination in predicting outcomes of immunocompetent patients with CM. Methods The demographic and clinical data of patients with CM were collected and analyzed. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1–4) outcome groups. Prognostic model was created and receiver-operating characteristic curve analyses were conducted. Results A total of 156 patients were included in our study. Patients with higher age at onset (p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), Glasgow Coma Scale (GCS) score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes. Logistic regression analysis was used to create a combined score which had a higher AUC (0.815) than those factors used alone for predicting outcome. Conclusions Our study shows that a prediction model based on clinical characteristics had satisfactory accuracy in prognostic prediction. Early recognition of CM patients at risk of poor prognosis using this model would be helpful in providing timely management and therapy to improve outcomes and to identify individuals who warrant early follow-up and intervention. …

Abstract Background Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system that can cause significant morbidity and mortality. Although several prognostic factors have been identified, their clinical efficacy and use in combination to predict outcomes in immunocompetent patients with CM are not clear. Therefore, we aimed to determine the utility of those prognostic factors alone or in combination in predicting outcomes of immunocompetent patients with CM. Methods The demographic and clinical data of patients with CM were collected and analyzed. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1–4) outcome groups. Prognostic model was created and receiver-operating characteristic curve analyses were conducted. Results A total of 156 patients were included in our study. Patients with higher age at onset (p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), Glasgow Coma Scale (GCS) score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes. Logistic regression analysis was used to create a combined score which had a higher AUC (0.815) than those factors used alone for predicting outcome. Conclusions Our study shows that a prediction model based on clinical characteristics had satisfactory accuracy in prognostic prediction. Early recognition of CM patients at risk of poor prognosis using this model would be helpful in providing timely management and therapy to improve outcomes and to identify individuals who warrant early follow-up and intervention. …

Abstract Purpose Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA). Methods Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated. Results A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline. Conclusion Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes. …

Abstract Background Bacterial meningitis caused by non-typhoid Salmonella can be a fatal condition which is more common in low and middle-income countries. Case presentation We report the case of a Salmonella meningitis in a Belgian six-month old male infant. The first clinical examination was reassuring, but after a few hours, his general state deteriorated. A blood test and a lumbar puncture were therefore performed. The cerebrospinal fluid analysis was compatible with a bacterial meningitis which was later identified by the NRC (National Reference Center) as Salmonella enterica serovar Durban. Conclusions In this paper, we present the clinical presentation, genomic typing, and probable sources of infection for an unusually rare serovar of Salmonella. Through an extended genomic analysis, we established its relationship to historical cases with links to Guinea. …

Abstract Campylobacter spp. is a gram-negative bacillus that causes infectious enteritis and consists of several species, including Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus. Although C. jejuni and C. coli cause infectious enteritis primarily in immunocompetent hosts, C. fetus causes extraintestinal infections such as septicemia, meningitis, and perinatal infections in immunocompromised hosts, as well as myopericarditis in rare cases. Only a few cases of infectious myo(peri)carditis associated with C. coli in immunocompetent hosts have been reported. These studies concentrated on antecedent C. coli enterocolitis and never demonstrated a positive culture in the pericardial fluid. A 72-year-old Japanese man presented with a 2-week fever, cough, and vomiting lasting. He was on hemodialysis for polycystic kidney disease, as well as medication for diabetes and hypertension. A chest computed tomography (CT) scan and a transthoracic echocardiogram revealed bilateral pleural fluid and large pericardial fluid at the time of admission. C. coli was identified from blood culture samples and blood-tinged pericardial fluid. He was successfully treated with antibacterial chemotherapy as well as pericardial fluid drainage and was discharged from the hospital with no complications. In this case, the presence of C. coli in the pericardial fluid confirmed the diagnosis of C. coli pericarditis. C. coli may cause septic pericarditis in immunocompromised hosts, despite typically causing only enteritis. …

Abstract Campylobacter spp. is a gram-negative bacillus that causes infectious enteritis and consists of several species, including Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus. Although C. jejuni and C. coli cause infectious enteritis primarily in immunocompetent hosts, C. fetus causes extraintestinal infections such as septicemia, meningitis, and perinatal infections in immunocompromised hosts, as well as myopericarditis in rare cases. Only a few cases of infectious myo(peri)carditis associated with C. coli in immunocompetent hosts have been reported. These studies concentrated on antecedent C. coli enterocolitis and never demonstrated a positive culture in the pericardial fluid. A 72-year-old Japanese man presented with a 2-week fever, cough, and vomiting lasting. He was on hemodialysis for polycystic kidney disease, as well as medication for diabetes and hypertension. A chest computed tomography (CT) scan and a transthoracic echocardiogram revealed bilateral pleural fluid and large pericardial fluid at the time of admission. C. coli was identified from blood culture samples and blood-tinged pericardial fluid. He was successfully treated with antibacterial chemotherapy as well as pericardial fluid drainage and was discharged from the hospital with no complications. In this case, the presence of C. coli in the pericardial fluid confirmed the diagnosis of C. coli pericarditis. C. coli may cause septic pericarditis in immunocompromised hosts, despite typically causing only enteritis. …

Abstract Background Certain bacterial infectious diseases are categorized as notifiable infectious diseases in China. Understanding the time-varying epidemiology of bacterial infections diseases can provide scientific evidence to inform prevention and control measures. Methods Yearly incidence data for all 17 major notifiable bacterial infectious diseases (BIDs) at the province level were obtained from the National Notifiable Infectious Disease Reporting Information System in China between 2004 and 2019. Of them 16 BIDs are divided into four categories, respiratory transmitted diseases (RTDs, 6 diseases), direct contact/fecal-oral transmitted diseases (DCFTDs, 3 diseases), blood-borne/sexually transmitted diseases (BSTDs, 2 diseases), and zoonotic and vector-borne diseases (ZVDs, 5 diseases), and neonatal tetanus is excluded in the analysis. We characterized the demographic, temporal, and geographical features of the BIDs and examined their changing trends using a joinpoint regression analysis. Results During 2004‒2019, 28 779 thousand cases of BIDs were reported, with an annualized incidence rate of 134.00 per 100 000. RTDs were the most commonly reported BIDs, accounting for 57.02% of the cases (16 410 639/28 779 000). Average annual percent changes (AAPC) in incidence were − 1.98% for RTDs, − 11.66% for DCFTDs, 4.74% for BSTDs, and 4.46% for ZVDs. Females had a higher incidence of syphilis than males, and other BIDs were more commonly reported in males. Among 0-5-year-olds, the diseases with the largest increases in incidence were pertussis (15.17% AAPC) and scarlet fever (12.05%). Children and students had the highest incidence rates of scarlet fever, pertussis, meningococcal meningitis, and bacillary dysentery. Northwest China had the highest incidence of RTDs, while South and East China had the highest incidences of BSTDs. Laboratory confirmation of BIDs increased from 43.80 to 64.04% during the study period. Conclusions RTDs and DCFTDs decreased from 2004 to 2019 in China, while BSTDs and ZVDs increased during the same period. Great attention should be paid to BSTDs and ZVDs, active surveillance should be strengthened, and timely control measures should be adopted to reduce the incidence. …

Purpose of review The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide. Recent findings Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis. Summary We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide.

Purpose of review Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually. Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no typical clinical features, its diagnosis is frequently misdiagnosing by other infections. Recent findings Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies, intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of cerebrospinal fluid parameters. Summary Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease in humans, as well as the disease control in animals and prevention based on occupational hygiene and food hygiene.

To the Editor We read with interest the recent Review on bacterial meningitis and agree that prompt diagnosis and early adequate antibiotic therapy are crucial for the prognosis. Although polymerase chain reaction (PCR) tests are extremely useful both for differentiating between bacterial and aseptic meningitis and for bacterial identification, we believe that the role of immunochromatographic tests (ICTs) should not be overlooked.

To the Editor The recent Review on bacterial meningitis is both timely and relevant, given that a considerable amount of time has passed since the last consensus statement or guidelines on bacterial meningitis. Despite recent improvements in management of bacterial meningitis, there is still a long way to go to attain the goals set by the World Health Organization, which provided an ambitious plan to address meningitis and its consequences by 2030.

In Reply In response to the Review article on bacterial meningitis, Dr Ait-Ali and colleagues describe the usefulness of the S pneumoniae ICT that can be performed on CSF of patients with suspected pneumococcal meningitis. I agree that this is a very sensitive and specific test for pneumococcal meningitis, and is particularly useful in hospitals without access to multiplex PCR assays. The S pneumoniae immunochromatographic test is also less expensive and faster than PCR assays and is an invaluable tool, especially in resource-limited countries where it has been evaluated.

We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa’s laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to hospital.

Abstract In this case report, we describe two unusual presentations of varicella-zoster virus (VZV) reactivation without rash, a condition known as Zoster Sine Herpete (ZSH). In Case 1, a 58-year-old woman presented with severe right-sided chest pain under her breast that radiated to the ipsilateral back. After the initial workup ruled out cardiac and musculoskeletal etiologies, the characteristic dermatomal distribution of pain made us suspect VZV reactivation. A diagnosis of ZSH was made with positive VZV IgG and IgM serologies and symptomatic relief after famciclovir treatment. In Case 2, a 43-year-old woman presented with a severe headache and resolved sharp right flank pain. She was diagnosed with varicella meningitis after cerebrospinal fluid showed positive VZV DNA. Intravenous acyclovir treatment resulted in symptom resolution. The most common presentation of VZV reactivation is Herpes Zoster, or shingles, making ZSH a frequently missed diagnosis. High clinical suspicion is warranted to prevent life-threatening complications of ZSH. …

Abstract In this case report, we describe two unusual presentations of varicella-zoster virus (VZV) reactivation without rash, a condition known as Zoster Sine Herpete (ZSH). In Case 1, a 58-year-old woman presented with severe right-sided chest pain under her breast that radiated to the ipsilateral back. After the initial workup ruled out cardiac and musculoskeletal etiologies, the characteristic dermatomal distribution of pain made us suspect VZV reactivation. A diagnosis of ZSH was made with positive VZV IgG and IgM serologies and symptomatic relief after famciclovir treatment. In Case 2, a 43-year-old woman presented with a severe headache and resolved sharp right flank pain. She was diagnosed with varicella meningitis after cerebrospinal fluid showed positive VZV DNA. Intravenous acyclovir treatment resulted in symptom resolution. The most common presentation of VZV reactivation is Herpes Zoster, or shingles, making ZSH a frequently missed diagnosis. High clinical suspicion is warranted to prevent life-threatening complications of ZSH. …

AbstractBackgroundSevere bacterial infections (SBI) in otherwise healthy children are rare and may represent an underlying impairment of the immune system including primary immunodeficiency (PID). However, it is unclear if and how children should be assessed.MethodsWe retrospectively analyzed data from hospital records of previously healthy children aged 3 days to 18 years with SBI including pleuropneumonia, meningitis, and/or sepsis. Patients were diagnosed or immunologically followed-up between 2013/01/01 and 2020/03/31.ResultsOut of 432 children with SBI, 360 children could be analyzed. Follow-up data were available for 265 (74%) children, of whom 244 children (92%) had immunological testing. Laboratory abnormalities were found in 51 of 244 patients (21%), with 3 deaths (1%). There were 14 (6%) children with immunodeficiency considered clinically relevant (3 complement deficiencies, 1 autoimmune neutropenia, 10 humoral immunodeficiencies) and 27 (11%) with milder humoral abnormalities or findings suggestive of delayed adaptive immune maturation.ConclusionsA substantial proportion of children with SBI may benefit from routine immunological testing, revealing (potentially) clinically relevant impaired immune function in 6-17% of children. The identification of immune abnormalities allows for specific counselling of families and optimization of preventive measures such as booster vaccinations to avoid future SBI episodes.

BackgroundThe cryptococcal antigen (CrAg) test was proposed as a rapid diagnostic tool to identify cryptococcal meningitis in patients suffering from AIDS. Several studies have demonstrated its diagnostic performance in cryptococcal meningitis. However, the diagnostic performance of the CrAg test in serum or bronchoalveolar lavage fluid in patients with pulmonary cryptococcosis remains uncertain. Therefore, the purpose of this systematic review is to summarise the evidence concerning diagnostic performance of the CrAg test in patients with pulmonary cryptococcosis. Methods and analysisDatabases such as PubMed, EMBASE, Cochrane Database of Systematic Reviews, Web of Science, ClinicalTrials.gov, International Clinical Trials Registry Platform, Wanfang Database and China National Knowledge Infrastructure will be searched systematically. The titles and abstracts will be reviewed by two independent reviewers. The Quality Assessment of Diagnostic Accuracy Studies 2 tool will be used to evaluate the risk of bias and clinical applicability of each study. Potential sources of heterogeneity will be investigated through visual inspection of the paired forest plots and summary receiver operating characteristic plots. The pooled summary statistics for the area under the curve, sensitivities, specificities, likelihood ratios and diagnostic ORs with 95% CI will be reported. Ethics and disseminationThe underlying study is based on published articles thus does not require ethical approval. The findings of the systematic review and meta-analysis will be published in a peer-reviewed journal and disseminated in various scientific conferences and seminars. PROSPERO registration numberCRD42022373321. …

Abstract Background Serogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana’s meningitis belt. Methods Polymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran–Armitage trend test. Results Of the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P < 0.01), and serogroup W showed a downward trend (P < 0.01). However, no significant trend was observed for any other serogroup. Conclusion This study showed the emergence of serogroup X, a non-vaccine type, as the predominant N. meningitidis serogroup in the wake of a declining serogroup W in Ghana’s meningitis belt. …

Abstract Objective Cryptococcal meningitis (CM) threatens people’s health and is the main cause of opportunistic fungus-related death in acquired immune deficiency syndrome (AIDS) patients. Herein, we investigate the clinical characteristics and prognostic factors of AIDS patients with Cryptococcus neoformans in Wenzhou, Zhejiang Province, China. Methods Our study enrolled AIDS patients diagnosed with Cryptococcus neoformans infection who were hospitalised in our hospital. They were divided into Group A (32 patients with CM) and Group B (28 patients without CM) according to their diagnosis. The differences between the two groups of patients’ clinical symptoms, imaging examinations and laboratory examinations were observed. Statistical methods were used to analyse the difference in prognosis between the two groups. Results Headache and fever were the most common clinical characteristics for patients with CM, while respiratory symptoms and fever were the most common clinical characteristics for patients without CM. The positive rate of cryptococcal capsular antigen, India ink staining and culture in the cerebrospinal fluid examination was higher in the CM patients than in the non-CM patients. The overall morbidity and mortality rate after systemic antifungal therapy was higher in the CM patients than in the non-CM patients. A higher incidence of headache, impaired consciousness, nuchal rigidity, first intracranial pressure > 200 mmH2O and mortality was observed in the CM patients than in the non-CM patients. Multifactorial logistic regression analysis showed that headache risk factors affecting the patient’s prognosis at 12 weeks. Conclusion Patients with AIDS diagnosed with Cryptococcus neoformans infection have insidious clinical symptoms in the early stage, and their manifestation is often non-specific, resulting in poor prognosis and high mortality among CM patients compared to patients without CM. Therefore, early identification and timely antifungal therapy before the disease progresses to meningitis are of great value in improving the survival rate of patients. …

Worldwide maternal vaccination against group B Streptococcus (GBS), a pathogen that can cause morbidity and mortality in pregnant people and their infants, could avoid 214 300 cases of severe disease—which often present as meningitis and sepsis—in their children, as well as prevent 31 100 infant deaths, among other outcomes, according to estimates based on 140 million pregnant women from 183 countries.

by Olivie C. Namuju, Proscovia M. Namuwenge, Richard Kwizera, Emmanuel Obuya, Paul Kirumira, Rose Naluyima, Cynthia Ahimbisibwe, JaneFrancis Ndyetukira, Hawa Nakato, Robert Kirungi, Jane Gakuru, Samuel Junju, Edwin Nuwagira, Morris Rutakagirwa, Sara Nsibirwa, Vennie Nabitaka, Elizabeth Nalintya, Edward Mpoza, Conrad K. Muzoora, Abdu K. Musubire, David R. Boulware, David B. Meya Introduction Health workers’ failure to adhere to guidelines for screening, diagnosis and management of HIV-associated cryptococcal meningitis (CM) remains a significant public health concern. We aimed to assess adherence to the standards of care and management of HIV patients at risk of CM per the MoH guidelines and assess stock management of CM supplies in the period of January to June 2021 at selected public health facilities (HFs) in Uganda. Methods The study employed an observational cross-sectional design to assess the level of adherence of health workers to standards of clinical care and management of HIV positive patients at risk of CM as per the clinical guidelines for Uganda, and stock management of CM supplies in the period of January to June 2021in selected public health facilities. The study team used a survey guide designed by MoH to assess and score the screening, diagnosis and management practices of Health Facilities towards CM. Scoring was categorized as red (< 80%), light green (80%-95%), and dark green (˃95%) in the order from worst to best adherence. The data was transcribed into a spread sheet and analysed using STATA–v15. Results The study team visited a total of 15 public health facilities including 5 general hospitals, 9 regional referral hospitals (RRHs) and 1 National Referral hospital (NRH). The mean score for adherence to screening and management of CM for all the combined facilities was 15 (64.7%) classified as red. 10 (66.7%) HFs had not performed a baseline CD4 test for eligible patients within 2 weeks of ART initiation. With regards to treatment, 9 (60%) of the HFs were scored as light green on knowledge of the procedure for reconstituting intravenous Liposomal Amphotericin B. None of the HFs visited had potassium chloride tablets in stock. Conclusion Major MoH guidelines are generally not being adhered to by health workers while managing cryptococcal meningitis. It is vital that government and implementing partners regularly support HFs with training, mentorship, and support supervision on CM management to improve adherence to CM screening and treatment guidelines. …

by Jasmin Nicole Nessler, Andrea Tipold Steroid responsive meningitis arteritis (SRMA) is an aberrant Th2-mediated systemic inflammatory disease in dogs. The etiopathogenesis still remains unclear as no triggering pathogen or autoantigen could be found so far. Hypothesis. Large high-density peptide microarrays are a suitable screening method to detect possible autoantigens which might be involved in the pathogenesis of SRMA. Methods. The IgA and IgG profile of pooled serum samples of 5 dogs with SRMA and 5 dogs with neck pain due to intervertebral disc herniation (IVDH) without ataxia or paresis were compared via commercially available high-density peptide microarrays (Discovery Microarray) containing 29,240 random linear peptides. Canine distemper virus nucleoprotein (CDVN) served as positive control as all dogs were vaccinated. Common motifs were compared to amino acid sequences of known proteins via databank search. One suitable protein was manually selected for further analysis with a smaller customized high-density peptide microarray. Results. Pooled serum of dogs with SRMA and IVDH showed different IgA and IgG responses on Discovery Microarray. Only top IgG responses of dogs with SRMA showed a common motif not related to the control protein CDVN. This common motif is part of the interleukin 1 receptor antagonist protein (IL1Ra). On IL1Ra, dogs with SRMA displayed IgA binding to an additional epitope, which dogs with IVDH did not show. Discussion. IL1Ra is an anti-inflammatory acute phase protein. Different immunoglobulin binding patterns on IL1Ra could be involved in the pathogenesis of SRMA and IL1Ra might be developed as future biomarker for SRMA.

Abstract Background Serogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana’s meningitis belt. Methods Polymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran–Armitage trend test. Results Of the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P < 0.01), and serogroup W showed a downward trend (P < 0.01). However, no significant trend was observed for any other serogroup. Conclusion This study showed the emergence of serogroup X, a non-vaccine type, as the predominant N. meningitidis serogroup in the wake of a declining serogroup W in Ghana’s meningitis belt. …

Abstract Objective Cryptococcal meningitis (CM) threatens people’s health and is the main cause of opportunistic fungus-related death in acquired immune deficiency syndrome (AIDS) patients. Herein, we investigate the clinical characteristics and prognostic factors of AIDS patients with Cryptococcus neoformans in Wenzhou, Zhejiang Province, China. Methods Our study enrolled AIDS patients diagnosed with Cryptococcus neoformans infection who were hospitalised in our hospital. They were divided into Group A (32 patients with CM) and Group B (28 patients without CM) according to their diagnosis. The differences between the two groups of patients’ clinical symptoms, imaging examinations and laboratory examinations were observed. Statistical methods were used to analyse the difference in prognosis between the two groups. Results Headache and fever were the most common clinical characteristics for patients with CM, while respiratory symptoms and fever were the most common clinical characteristics for patients without CM. The positive rate of cryptococcal capsular antigen, India ink staining and culture in the cerebrospinal fluid examination was higher in the CM patients than in the non-CM patients. The overall morbidity and mortality rate after systemic antifungal therapy was higher in the CM patients than in the non-CM patients. A higher incidence of headache, impaired consciousness, nuchal rigidity, first intracranial pressure > 200 mmH2O and mortality was observed in the CM patients than in the non-CM patients. Multifactorial logistic regression analysis showed that headache risk factors affecting the patient’s prognosis at 12 weeks. Conclusion Patients with AIDS diagnosed with Cryptococcus neoformans infection have insidious clinical symptoms in the early stage, and their manifestation is often non-specific, resulting in poor prognosis and high mortality among CM patients compared to patients without CM. Therefore, early identification and timely antifungal therapy before the disease progresses to meningitis are of great value in improving the survival rate of patients. …

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 108 Issue: 4 Pages: 851-856 …

An 87-year-old man presented to the ER with a 14-hour history of fever, headache, disorientation, and vomiting. He had a medical history of COPD, hypertension and atrial fibrillation with continuous warfarin treatment, and suffered from periapical periodontitis. The patient had no other health conditions and was active for his age, engaging daily in physical activities.

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].

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. …

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.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.