Central nervous system infections in the tropics.

PURPOSE OF REVIEW: Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. RECENT FINDINGS: In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. SUMMARY: A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.

Solid organ transplant-related central nervous system infections.

PURPOSE OF REVIEW: Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause. RECENT FINDINGS: New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations. SUMMARY: The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

BACKGROUND: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. METHODS: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. RESULTS: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. CONCLUSION: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.

Clinical course and peculiarities of Parechovirus and Enterovirus central nervous system infections in newborns: a single-center experience.

Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic meningitis, encephalitis, and myocarditis. Our study aimed to describe the clinical presentations and peculiarities of CNS infection by HpEV and EV in neonates. This is a single-center retrospective study at Istituto Gaslini, Genoa, Italy. Infants aged ≤ 30 days with a CSF RTq-PCR positive for EV or HpEV from January 1, 2022, to December 1, 2023, were enrolled. Each patient's record included demographic data, blood and CSF tests, brain MRI, therapies, length of stay, ICU admission, complications, and mortality. The two groups were compared to identify any differences and similarities. Twenty-five patients (15 EV and 10 HpEV) with a median age of 15 days were included. EV patients had a more frequent history of prematurity/neonatal respiratory distress syndrome (p = 0.021), more respiratory symptoms on admission (p = 0.012), and higher C-reactive protein (CRP) levels (p = 0.027), whereas ferritin values were significantly increased in HpEV patients (p = 0.001). Eight patients had a pathological brain MRI, equally distributed between the two groups. Three EV patients developed myocarditis and one HpEV necrotizing enterocolitis with HLH-like. No deaths occurred.  Conclusion: EV and HpEV CNS infections are not easily distinguishable by clinical features. In both cases, brain MRI abnormalities are not uncommon, and a severe course of the disease is possible. Hyper-ferritinemia may represent an additional diagnostic clue for HpEV infection, and its monitoring is recommended to intercept HLH early and initiate immunomodulatory treatment. Larger studies are needed to confirm our findings. What is Known: • Parechovirus and Enteroviruses are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants. • The clinical course and distinguishing features of Parechovirus and Enterovirus central nervous system infections are not well described. What is New: • Severe disease course, brain MRI abnormalities, and complications are not uncommon in newborns with Parechovirus and Enteroviruses central nervous system infections. • Hyper-ferritinemia may represent an additional diagnostic clue for Parechovirus infection and its monitoring is recommended.

Characteristics and Risk Factors of Central Nervous System Infection in Children With Febrile Seizures.

OBJECTIVE: The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil. METHODS: A retrospective cross-sectional study was performed from January 2017 to December 2021. RESULTS: A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection. CONCLUSIONS: When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture.

Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019.

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.

Varicella zoster virus: an under-recognised cause of central nervous system infections?

BACKGROUND: Varicella zoster virus (VZV) causes infections of the central nervous system (CNS) manifesting as meningitis or encephalitis. It is not commonly tested in CNS infections when compared with enterovirus (EV) and herpes simplex virus 1 (HSV-1) and 2 (HSV-2). Cerebrospinal fluid (CSF) findings of viral CNS infections are thought to be comparable. AIMS: To describe the manifestations of VZV CNS infections and ascertain if there is a predominant syndrome. To compare CSF parameters of VZV with EV, HSV-1 and HSV-2. METHODS: Retrospective study at two hospitals in Brisbane, reviewing medical notes and laboratory information system for results between January 2001 and 2019. The following parameters were recorded - disease classification, presence of rash, duration of symptoms prior to hospitalisation, length of admission, duration of antiviral treatment and 30-day mortality. CSF biochemistry, cell count (differential), PCR for VZV, EV, HSV-1 and HSV-2 were recorded. Statistical analysis of CSF parameters included Student's t-test and linear regression. RESULTS: Incidence of meningitis was comparable to encephalitis (44 vs 39%) in 52 cases. CSF protein in VZV was significantly elevated compared with EV (median 1121 vs 569 mg/L; P < 0.001) as was CSF monocytosis (96% vs 61%; P < 0.001). CSF parameters between VZV, HSV-1 and HSV-2 were similar. VZV had a higher incidence than HSV-1 or 2, while it was tested one-third as often. CONCLUSIONS: VZV CNS infection cannot be predicted by syndrome. CSF findings are markedly different from EV but like HSV-1 and 2. VZV should be routinely tested with HSV-1 and 2 when viral CNS infection is suspected.

Caregiver's perspectives on the Central Nervous System infection illness trajectory among older persons with dementia in Northern Uganda-a qualitative community-based study.

BACKGROUND: Few studies have explored the Central Nervous System (CNS) infection illness trajectory among older persons with dementia in sub-Saharan African (SSA) settings. This study explored the Caregiver's perspectives on the Central Nervous System infection illness trajectory among the older persons with dementia in Northern Uganda. METHODS: This was a qualitative study conducted in Lira District northern Uganda in March 2022 amongst purposively selected 20 caregivers of the older persons aged 50 + years with a positive history of CNS infection and later life dementia. Data were collected using an in-depth interview guide. Audio recordings and field notes of the interviews were undertaken. The interviews generated data on the CNS infection illness trajectory from onset to the current demented state of the older persons. The audio-recorded interviews were transcribed verbatim before manual reflective thematic analysis. RESULTS: Older persons with a positive history of CNS infection illness and later life dementia in rural northern Uganda presented with symptoms of early life CNS infection illness ranging from neck pain, back pain, chronic headache, and fatigue. There were also manifestations of comorbidities particularly road traffic accidents involving traumatic injury to the head, neck, and spine, high blood pressure, chronic headache, and or their medications in the older person's trajectory to later life dementia. A plurality of healthcare which included both formal and informal healthcare medicines was sought and utilized for the treatment and care of the CNS infection illness and dementia by the older persons amidst improper diagnosis and mismanagement. CONCLUSIONS AND RECOMMENDATIONS: Older persons with early-life CNS infections illness and later-life dementia were reported to present with symptoms including neck pain, back pain, chronic headache, high blood pressure, and fatigue. The reported symptoms of CNS infection illness may be intertwined with co-morbidities particularly traumatic injury involving the head, neck, and spine, high blood pressure, and chronic headache. Healthcare professionals should integrate routine screening of older persons for the history of CNS infections, chronic headache, high blood pressure, trauma to the head, neck, and spine, and dementia and early treatment.

Viral Metagenomic Analysis of Cerebrospinal Fluid from Patients with Acute Central Nervous System Infections of Unknown Origin, Vietnam.

Central nervous system (CNS) infection is a serious neurologic condition, although the etiology remains unknown in >50% of patients. We used metagenomic next-generation sequencing to detect viruses in 204 cerebrospinal fluid (CSF) samples from patients with acute CNS infection who were enrolled from Vietnam hospitals during 2012-2016. We detected 8 viral species in 107/204 (52.4%) of CSF samples. After virus-specific PCR confirmation, the detection rate was lowered to 30/204 (14.7%). Enteroviruses were the most common viruses detected (n = 23), followed by hepatitis B virus (3), HIV (2), molluscum contagiosum virus (1), and gemycircularvirus (1). Analysis of enterovirus sequences revealed the predominance of echovirus 30 (9). Phylogenetically, the echovirus 30 strains belonged to genogroup V and VIIb. Our results expanded knowledge about the clinical burden of enterovirus in Vietnam and underscore the challenges of identifying a plausible viral pathogen in CSF of patients with CNS infections.

Enteric viruses circulating in undiagnosed central nervous system infections at tertiary hospital in São José do Rio Preto, São Paulo, Brazil.

Enterovirus (EV) is commonly associated with central nervous system (CNS) syndromes. Recently, gastroenteric viruses, including rotavirus (RVA), human astrovirus (HAstV), and norovirus (NoV), have also been associated with CNS neurological disorders. The aim of the present study was to investigate the presence of EV, RVA, HAst, and NoV associated to CNS infections with undiagnosed etiology in Northwest region of São Paulo State, Brazil, and to conduct the molecular characterization of the positive samples detected. A total of 288 cerebrospinal fluid samples collected from July to December 2017 were tested for EV and NoV by quantitative real-time polymerase chain reaction (RT-qPCR), HAstV by conventional RT-PCR, and RVA by enzyme-linked immunosorbent assay. Positive-EV samples were inoculated in cells lines, amplified by RT-PCR and sequenced. RVA, NoV, and HAstV were not detected. EV infection was detected in 5.5% (16/288), and five samples successful genotyped: echovirus 3 (E3) (1/5), coxsackie virus A6 (CVA6) (1/5), and coxsackie virus B4 (CVB4) (3/5). Meningitis was the main syndrome observed (12/16; 75%). CVA6, CVB4, and E3 were identified associated with aseptic meningitis. Reports of CVA6 associated with aseptic meningitis are rare, E3 had not been previously reported in Brazil, and epidemiological data on CVB4 in the country is virtually unknown. The present investigation illustrates the circulation of diverse EV types in a small regional sample set and in a short period of time, highlighting the importance of an active EV surveillance system in CNS infections. Enhanced understanding of undiagnosed CNS infections will assist in public health and health care planning.

Cerebrospinal fluid test results and associations with subsequent mental disorders, neurological diseases, and CNS infections: A population-based cohort study.

BACKGROUND: Cerebrospinal fluid (CSF) immune alterations have been associated with mental disorders, neurological disease, and CNS infections; however, comprehensive large-scale longitudinal CSF studies are lacking. METHODS: By using the Clinical Laboratory Information System (LABKA) Research Database in the Central Denmark Region (1994-2012), we included 15,030 individuals tested for CSF WBC, CSF/serum albumin ratio, IgG index, total protein, albumin, or IgG with follow-up for the risk of mental disorders, psychotropic prescriptions, neurological diseases, or CNS infections, estimated by Cox regression. RESULTS: Among individuals receiving a mental disorder diagnosis (N = 1,147) after a CSF test, 30·0% had an abnormal CSF test result, while for those with a neurological disease (N = 3,201), 39·9% had abnormal test results, and among individuals with CNS infections (N = 1,276), 73·0% had abnormal test results. Individuals with abnormal CSF test results had an increased risk of mental disorders (HR = 3·20; 95%CI = 2·86-3·59), neurological diseases (HR = 12·40; 95%CI = 11·65-13·20), and CNS infections (HR = 338·59; 95%CI = 299·06-383·35) compared to individuals not registered with a CSF test. However, the risk of mental disorders was higher (P < 0·001) after CSF test results within the normal range (HR = 4·45; 95%CI = 4·08-4·86), whereas for neurological diseases (HR = 9·72; 95%CI = 9·19-10·29) and CNS infections (HR = 55·17; 95%CI = 47·12-64·60), the risk was highest after abnormal CSF test results (all P < 0·001). The risk of organic mental disorders tended to be highest in individuals with abnormal CSF test results (HR = 19·30; 95%CI = 13·44-27·71) even though not significantly different from the risk in the group of individuals with CSF test results in the normal range (HR = 13·55; 95%CI = 9·36-19·60) (P ≥ 0·05). Abnormal CSF test results were associated with an elevated risk of psychotropic prescriptions (HR = 3·91; 95%CI = 3·66-4·18), as were CSF test results within the normal range (HR = 4·26; 95%CI = 4·03-4·51) (P < 0·05). CONCLUSIONS: Immunological CSF abnormalities are associated with an increased risk of mental disorders, neurological disease, and particularly CNS infections; however, the included CSF parameters were not specific for mental disorders and the relevant CSF biomarkers in psychiatry are yet to be discovered.

Direct next-generation sequencing diagnosis of echovirus 9 meningitis, France.

The prognosis of central nervous system infections caused by enteroviruses partially depends on the viral genotype, which is not provided by current point-of-care diagnostic methods. In this study, next-generation sequencing identified an echovirus 9 directly from the cerebrospinal fluid of a patient presenting with meningitis.

Epidemiology of patients with central nervous system infections, mainly neurosurgical patients: a retrospective study from 2012 to 2019 in a teaching hospital in China.

BACKGROUND: Central nervous system (CNS) infections are relatively rare but are associated with high mortality worldwide. Empirical antimicrobial therapy is crucial for the survival of patients with CNS infections, and should be based on the knowledge of the pathogen distribution and antibiotic sensitivities. The aim of this study was to investigate the features of pathogens in patients with CNS infections in North China and evaluate the risk factors for mortality and multi-drug-resistant (MDR) bacterial infections. METHODS: A retrospective study was conducted with patients with positive cerebrospinal fluid (CSF) cultures in a teaching hospital from January 2012 to December 2019. The following data were collected: demographic characteristics, laboratory data, causative organisms and antimicrobial sensitivity results. Data were analyzed with SPSS 16.0. Univariate analysis and binary logistic regression analyses were performed to identify the risk factors for mortality and MDR bacterial infections. RESULTS: A total of 72 patients were diagnosed with CNS infections, and 86 isolates were identified. The proportions of Gram-positive bacteria, Gram-negative bacteria and fungi were 59.3, 30.2 and 10.5%, respectively. The predominant Gram-positive bacteria was Coagulase-negative Staphylococci. Acinetobacter baumannii, Escherichia coli and Klebsiella spp. were the predominant Gram-negative bacteria. Compared to 2012-2015 years, the proportion of Gram-negative bacteria increased markedly during 2016-2019 years. Coagulase-negative Staphylococci, Streptococcus pneumoniae and Enterococcus faecium had 100% sensitivity to vancomycin, teicoplanin and linezolid. Acinetobacter baumannii and Klebsiella pneumoniae were 100% sensitive to tigecycline. Escherichia coli had 100% sensitivity to amikacin, meropenem and imipenem. The overall mortality rate in the 72 patients was 30.6%. In multivariate analysis, age > 50 years, pulmonary infections and CSF glucose level < the normal value were associated with poor outcomes. CSF adenosine deaminase level > the normal value and the presence of external ventricular drainage/lumbar cistern drainage were associated with MDR bacterial infections. CONCLUSIONS: The mortality rate due to CNS infections reached 30.6% in our study. The proportion of Gram-negative bacteria has increased markedly in recent years. We should give particular attention to patients with risk factors for mortality and MDR bacterial infections mentioned above.

Incidence and Distribution of the Pathogens Causing Central Nervous System Infections at the University Hospital of Korea.

BACKGROUND: The pathogens involved in central nervous system (CNS) infections are various, such as viruses, bacteria, and fungi, so a syndromic approach can be required. In addition, since their rapid and accurate detection is very crucial, molecular diagnostics using cerebrospinal fluid is becoming the emerging standard method. METHODS: The study was conducted retrospectively to identify the incidence and distribution patterns of the pathogens according to gender, age, season, and month and to analyze their codetection from August 2017 to July 2020. It was also conducted to investigate turn-around times (TATs) according to the detection method. The detection methods were FilmArray® Meningitis/Encephalitis (M/E) method (FilmArray), Cepheid® Xpert EV assay (Xpert), and Multiplex PCR method for five species of bacteria. RESULTS: The overall incidence for at least one pathogen was 13.9% (346/2,496). The highest incidence was shown in age group 4 (3 - 6 years), with 27.4%. The detection rates by FilmArray, Xpert, and Multiplex PCR method were 39.8%, 41.7%, and 0.4%, respectively. Enterovirus (EV) showed the highest incidence rate, which accounted for 37.0%. The distribution of the pathogens according to the age groups were the highest in age group 4, with 47.5% (168/354), followed by 27.4% (97/354) in age group 5. Of the ten cases in which bacteria were detected, S. agalactiae accounted for 60.0% (6/10), most of which occurred in age group 1. E. coli K1, L. monocytogenes, and N. meningitidis were not detected. In the viral distribution, EV accounted for the highest proportion in all age groups. The overall proportion of EV accounted for 87.6% (310/354), followed by human parechovirus with 2.8% (10/354). The most commonly detected season was summer, comprising 75.1%. A total of eight cases of co-detection with two pathogens accounted for 1.6% (8/507) in FilmArray. In FilmArray, all TATs were found to be shorter than Xpert. CONCLUSIONS: The information on the incidence and distribution patterns of the pathogens causing CNS infections and their rapid detection are critically important to clinicians in the management of immunocompromised patients, elderly, and children. The expeditious molecular diagnostics for these pathogens would be valuable in medical decisions by clinicians.

Nontraumatic coma in the pediatric intensive care unit: etiology, clinical characteristics and outcome

Background/aim: The purpose of this study was to evaluate the etiology, clinical characteristics, and outcome of nontraumatic coma (NTC) among children admitted to a pediatric intensive care unit (PICU). Materials and methods: A total of 159 children with NTC were included in the study. The modified Glasgow coma scale (GCS) was used to assess consciousness. Patients were classified with regard to etiology. For each patient, demographic and clinical characteristics, survival and degree of disability at PICU discharge were recorded. Results: Median age was 55 months (IQR: 17.0 - 109.0). The most common cause of NTC was neuroinfection (31.4%) followed by toxic- metabolic conditions (25.8%) and epileptic disorder (15.1%). There was no significant relationship between the level of encephalopathy at admission and NTC etiology. A total of 13 patients died (8.2%). Among the survivors, 61.6% were discharged without any neurologic deficit, 2.8% had severe neurologic disability, and 3.4% were in a vegetative state. Complete neurological recovery was significantly more common in patients with toxic metabolic disease, whereas neurological deficits were more frequent in patients with tuberculous meningo-encephalitis (P = 0.01 and P = 0.04, respectively). Higher pediatric risk of mortality III (PRISM III) score at PICU admission (Odds ratio: 1.51, 95% CI: 1.19 - 1.92; P < 0.001) was the only variable that was independently associated with mortality. The length of stay (LOS) at hospital (Odds ratio: 0.73, 95% CI: 0.58-0.91; P = 0.006) was associated with improved odds of survival. Conclusions: Although results obtained from this single-center study cannot be generalized to the pediatric population, the contribution to the literature in terms of the relationships between NTC etiology, and outcome can be crucial for clinical decision-making. We report neuroinfection as the most common cause of NTC, and the only factor that was closely associated with mortality was PRISM III score. Length of hospital stay was inversely correlated to patient mortality.

Long-Term Survival, Health, Social Functioning, and Education in Patients With an Enterovirus Central Nervous System Infection, Denmark, 1997-2016.

BACKGROUND: The long-term clinical course of patients with an enterovirus central nervous system infection (ECI) is poorly understood. METHODS: We performed a nationwide population-based cohort study of all Danish patients with ECI diagnosed 1997-2016 (n = 1745) and a comparison cohort from the general population individually matched on date of birth and sex (n = 17 450). Outcomes were categorized into mortality and risk of cancer and likely measures of neurological sequelae: neuropsychiatric morbidities, educational landmarks, use of hospital services, employment, receipt of disability pension, income, number of sick leave days, and nursing home residency. RESULTS: Mortality in the first year was higher among patients with ECI (mortality rate ratio [MRR] = 10.0; 95% confidence interval [CI], 4.17-24.1), but thereafter mortality was not higher (MMR = 0.94; 95% CI, 0.47-1.86). Long-term outcomes for patients with ECI were not inferior to those of the comparison cohort for risk of cancer, epilepsy, mental and behavioral disorders, dementia, depression, school start, school marks, high school education, use of hospital services, employment, receipt of disability pension, income, days of sick leave, or nursing home residency. CONCLUSIONS: Diagnosis of an ECI had no substantial impact on long-term survival, health, or social/educational functioning.

Not Just Endocarditis: Hospitalizations for Selected Invasive Infections Among Persons With Opioid and Stimulant Use Diagnoses-North Carolina, 2010-2018.

BACKGROUND: While increases in overdoses, viral hepatitis, and endocarditis associated with drug use have been well-documented in North Carolina, the full scope of invasive drug-related infections (IDRIs) has not. We characterized trends in IDRIs among hospitalized patients in North Carolina. METHODS: We compared invasive infections that were related or not related to drug use among hospitalized patients aged 18-55 years based on retrospective review of administrative records from 2010-2018. Hospitalizations for endocarditis, central nervous system/spine infections, osteomyelitis, and septic arthritis were labeled as IDRIs if discharge codes included opioid and/or amphetamine misuse. Trends, rates, and distributions were calculated. RESULTS: Among 44 851 hospitalizations for the specified infections, 2830 (6.3%) were IDRIs. The proportion of infections attributable to drug use increased from 1.5% (2010) to 13.1% (2018), and the rate grew from 1.2 to 15.1 per 100 000. Compared with those who had non-drug-related infections, patients with IDRIs were younger (median age, 35 vs 46 years), more likely to be non-Hispanic white (81% vs 56%), and had longer hospitalizations (median, 8 vs 6 days). 43% of hospitalizations for IDRIs involved infective endocarditis. CONCLUSIONS: The rate of IDRIs in North Carolina increased substantially during 2010-2018, indicating an urgent need for enhanced infection prevention, harm reduction, and addiction services aimed at community and inpatient settings.

Prevalence and Risk Factors of White Matter Lesions in Tibetan Patients Without Acute Stroke.

Background and Purpose- Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke. Methods- We undertook a retrospective analysis of medical records of patients treated at the People's Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods. Results- Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity. Conclusions- Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.

Impact of cerebrospinal fluid syndromic testing in the management of children with suspected central nervous system infection.

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1 year, with possible CNS infection and CSF pleocytosis (> 15 cells/mm3). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10) days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10) days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.

Clinical insights and epidemiology of central nervous system infection due to Cryptococcus neoformans/gattii species complexes: A prospective study from South India.

In the last two decades, central nervous system (CNS) cryptococcosis (CNSc) has emerged as a major opportunistic infection in the immunocompromised population of India. We have analyzed the clinical features of CNSc and epidemiology of Cryptococcus neoformans and Cryptococcus gattii. A total of 160 clinical isolates of C. neoformans/gattii recovered from CNSc patients were analyzed. The origin, clinical parameters, and imaging features of the patients were recorded, and clinical parameters were analyzed based on their human immunodeficiency virus (HIV) status and infecting species, namely, C. neoformans or C. gattii. Serotypes and mating types of the isolates were determined. Molecular typing was performed by polymerase chain reaction (PCR) fingerprinting using M13 microsatellite primer (GTG)5, and multilocus sequence typing (MLST). Majority of the patients were from Bangalore Urban, Karnataka. Among 160 cases 128 (80%) were HIV seropositive, and 32 (20%) were HIV negative. Middle-aged males (36-55 years) were highly affected. There were statistically significant differences in the clinical manifestations, imaging and CSF parameters of HIV coinfected and noninfected cases, whereas limited differences were observed in these parameters in the cases infected with C. neoformans and C. gattii. We identified 80% C. neoformans VNI, 8.75% VNII and 22.5% C. gattii (VGI), 8.75% C. tetragattii (VGIV) among clinical strains. This comprehensive study will contribute toward a better prognosis of CNS cryptococcosis patients during the hospital stay, treatment strategies for HIV coinfected and noninfected cases and will provide the molecular epidemiology of these two pathogenic fungal species in south India, which was unclear in this part of the country.