CNS infections in HIV Thakur, Kiran T
Current opinion in infectious diseases,
06/2020, Letnik:
33, Številka:
3
Journal Article
Recenzirano
Central nervous system (CNS) infections associated with HIV remain significant contributors to morbidity and mortality, particularly among people living with HIV (PLWH) in resource-limited settings ...worldwide. In this review, we discuss several recent important scientific discoveries in the prevention, diagnosis, and management around two of the major causes of CNS opportunistic infections-tuberculous meningitis (TBM) and cryptococcal meningitis including immune reconstitution syndrome (IRIS) associated with cryptococcal meningitis. We also discuss the CNS as a possible viral reservoir, highlighting Cerebrospinal fluid viral escape.
CNS infections in HIV-positive people in sub-Saharan Africa contribute to 15-25% of AIDS-related deaths. Morbidity and mortality in those is associated with delays in HIV diagnosis, lack of availability for antimicrobial treatment, and risk of CNS IRIS. The CNS may serve as a reservoir for replication, though it is unclear whether this can impact peripheral immunosuppression.
Significant diagnostic and treatment advances for TBM and cryptococcal meningitis have yet to impact overall morbidity and mortality according to recent data. Lack of early diagnosis and treatment initiation, and also maintenance on combined antiretroviral treatment are the main drivers of the ongoing burden of CNS opportunistic infections. The CNS as a viral reservoir has major potential implications for HIV eradication strategies, and also control of CNS opportunistic infections.
The first case of paralytic poliomyelitis in nearly a decade in the US was discovered in a 20‐year‐old unvaccinated man from Rockland County, New York, in July 2022, who developed acute flaccid ...myelitis. The isolated virus from stool sampling was found to be a circulating vaccine‐derived poliovirus type 2, derived from the oral polio vaccine. Since the discovery of this case, local wastewater surveillance has revealed evidence of circulating vaccine‐derived poliovirus type 2 in local counties, as well as in New York City, representing community transmission. In the wake of the coronavirus disease 2019 pandemic, routine vaccination administration has declined globally, with increasing numbers of communities not vaccinated for poliovirus. Now, with evidence of local community transmission, the clinical implication for at‐risk unvaccinated individuals is significant. Here, we review the epidemiological origin of this discovered strain of poliovirus, national and international methods of surveillance for poliovirus, and neurological features of poliovirus. We also highlight the opportunities and challenges involved in monitoring suspected cases, as well as the unique role neurologists might play in national and global poliomyelitis surveillance. ANN NEUROL 2022;92:725–728
Purpose of Review
Neurological conditions associated with HIV/AIDS including central nervous system (CNS), opportunistic infections (OI), chronic conditions including HIV-associated neurocognitive ...disorder, and cerebrospinal fluid (CSF) viral escape remain major contributors to morbidity and mortality worldwide. CNS infections in HIV-infected patients are often challenging to diagnose by traditional microbiological testing, impacting treatment and outcome.
Recent Findings
Recent advances in diagnostic techniques, including metagenomic next-generation sequencing (mNGS), are changing the landscape of microbiological testing, mainly in resource-rich settings. Pathogen discovery techniques offer a hypothesis-free approach to diagnostic testing, yielding comprehensive analysis of microbial genetic material. Given the extent of genetic material produced, deep sequencing tools not only hold promise in the diagnosis of CNS infections but also in defining key pathogenic steps which have previously been unanswered.
Summary
Significant challenges remain to implementing pathogen discovery techniques in routine clinical practice including cost, expertise and infrastructure needed including laboratory and bioinformatics support, and sample contamination risk. The use in resource-limited regions where the burden of CNS complications due to HIV/AIDS is highest remains poorly defined. Though, major opportunities utilizing pathogen discovery techniques exist to enhance surveillance and diagnosis and improve our understanding of mechanisms of neuroinvasion in CNS conditions associated with HIV.
•Headache, altered mental status and weakness are the most common reported neurological symptoms in children.•Severe complications such as demyelinating disease, stroke, and encephalopathy have also ...been reported.•Inflammation, direct or indirect, may contribute to the neurological consequence in children.•Further studies are needed to define the short and long-term impact of COVID-19 infection in children.
Coronavirus disease 2019 (COVID-19) usually leads to a mild infectious disease course in children, but serious complications may occur in conjunction with both acute infection and associated phenomena such as the multisystem inflammatory syndrome in children (MIS-C). Neurological symptoms, which have been predominantly reported in adults, range from mild headache to seizure, peripheral neuropathy, stroke, demyelinating disorders, and encephalopathy. Similar to respiratory and cardiac manifestations of COVID-19, neurological complications present differently based on age and underlying comorbidities. This review provides a concise overview of the neurological conditions seen in the context of COVID-19, as well as potential mechanisms and long-term implications of COVID-19 in the pediatric population from literature reviews and primary data collected at NewYork-Presbyterian Morgan Stanley Children's Hospital.
One year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to summarize the frequency of neurologic manifestations reported in patients with COVID-19 and to investigate ...the association of these manifestations with disease severity and mortality.
We searched PubMed, Medline, Cochrane library, ClinicalTrials.gov, and EMBASE for studies from December 31, 2019, to December 15, 2020, enrolling consecutive patients with COVID-19 presenting with neurologic manifestations. Risk of bias was examined with the Joanna Briggs Institute scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% confidence intervals (CIs) were calculated for neurologic manifestations. Odds ratio (ORs) and 95% CIs were calculated to determine the association of neurologic manifestations with disease severity and mortality. Presence of heterogeneity was assessed with
, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.
Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 patients with COVID-19, 89% of whom were hospitalized. Forty-one neurologic manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurologic symptoms included fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%), and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurologic diagnosis (pooled prevalence 2%). In patients with COVID-19 ≥60 years of age, the pooled prevalence of acute confusion/delirium was 34%, and the presence of any neurologic manifestations in this age group was associated with mortality (OR 1.80, 95% CI 1.11-2.91).
Up to one-third of patients with COVID-19 analyzed in this review experienced at least 1 neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with nearly a doubling of mortality. Results must be interpreted with the limitations of observational studies and associated bias in mind.
PROSPERO CRD42020181867.
: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral ...therapy (cART). Importantly, growing evidence shows that the central nervous system (CNS) may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Although there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain. In many resource-limited settings, antiretrovirals considered second or third line in the United States, which carry substantial neurotoxicity, remain mainstays of treatment, and patients continue to present with severe immunosuppression and CNS opportunistic infections. Despite this, increased global access to cART has coincided with an aging HIV-positive population with cognitive sequelae, cerebrovascular disease, and peripheral neuropathy. Further neurological research in low-income and middle-income countries (LMICs) is needed to address the burden of neurological complications in HIV-positive patients, particularly regarding CNS viral reservoirs and their effects on eradication.
To better understand the heterogeneous population of patients with new-onset refractory status epilepticus (NORSE), we studied the most severe cases in patients who presented with new-onset ...super-refractory status epilepticus (NOSRSE).
We report a retrospective case series of 26 adults admitted to the Columbia University Irving Medical Center neurologic intensive care unit (NICU) from February 2009 to February 2016 with NOSRSE. We evaluated demographics, diagnostic studies, and treatment course. Outcomes were modified Rankin Scale score (mRS) at hospital discharge and most recent follow-up visit (minimum of 2 months post discharge), NICU and hospital length of stay, and long-term antiepileptic drug use.
Of the 252 patients with refractory status epilepticus, 27/252 had NORSE and 26/27 of those had NOSRSE. Age was bimodally distributed with peaks at 27 and 63 years. The majority (96%) had an infectious or psychiatric prodrome. Etiology was cryptogenic in 73%, autoimmune in 19%, and infectious in 8%. Seven patients (27%) underwent brain biopsy, autopsy, or both; 3 (12%) were diagnostic (herpes simplex encephalitis, candida encephalitis, and acute demyelinating encephalomyelitis). On discharge, 6 patients (23%) had good or fair outcome (mRS 0-3). Of the patients with long-term follow-up data (median 9 months, interquartile range 2-22 months), 12 patients (71%) had mRS 0-3.
Among our cohort, nearly all patients with NORSE had NOSRSE. The majority were cryptogenic with few antibody-positive cases identified. Neuropathology was diagnostic in 12% of cases. Although only 23% of patients had good or fair outcome on discharge, 71% met these criteria at follow-up.
Recent outbreaks of poliomyelitis in countries that have been free of cases for decades highlight the challenges of eradicating polio in a globalized interconnected world beset with a novel viral ...pandemic. We provide an epidemiological update, advancements in vaccines, and amendments in public health strategy of poliomyelitis in this review.
Last year, new cases of wild poliovirus type 1 (WPV1) were documented in regions previously documented to have eradicated WPV1 and reports of circulating vaccine-derived poliovirus type 2 (cVDPV2) and 3 (cVDPV3) in New York and Jerusalem made international headlines. Sequencing of wastewater samples from environmental surveillance revealed that the WPV1 strains were related to WPV1 lineages from endemic countries and the cVDPV2 strains from New York and Jerusalem were not only related to each other but also to environmental isolates found in London. The evidence of importation of WPV1 cases from endemic countries, and global transmission of cVDPVs justifies renewed efforts in routine vaccination programs and outbreak control measures that were interrupted by the COVID-19 pandemic. After the novel oral poliovirus vaccine type 2 (nOPV2) received emergency authorization for containment of cVDPV2 outbreaks in 2021, subsequent reduced incidence, transmission rates, and vaccine adverse events, alongside increased genetic stability of viral isolates substantiates the safety and efficacy of nOPV2. The nOPV1 and nOPV3 vaccines, against type 1 and 3 cVDPVs, and measures to increase accessibility and efficacy of inactivated poliovirus vaccine (IPV) are in development.
A revised strategy utilizing more genetically stable vaccine formulations, with uninterrupted vaccination programs and continued active surveillance optimizes the prospect of global poliomyelitis eradication.
Conditions such as community-acquired bacterial meningitis and tropical neurological infections remain major drivers of death and disability-adjusted life-years (DALYs) worldwide.1 Infections like ...neurocysticercosis, HIV, and Zika virus not only cause neurological injury in the acute setting, but also contribute substantially to long-term sequelae, such as neurodevelopmental disorders, cerebrovascular disease, epilepsy, or cognitive impairment. With widespread availability of antiretroviral therapy, incidence rates of CNS opportunistic infections for patients with HIV have dropped considerably, by more than 75% of cases in many countries.16 In patients with multiple sclerosis, appropriate risk stratification has led to notable preventive measures for progressive multifocal leukoencephalopathy.17 But perhaps the best example of a prevention and surveillance system for a neuroinfectious disease is the Global Polio Eradication Initiative (GPEI), launched in 1988, which has reduced paralytic poliomyelitis cases by more than 99%.18 High-quality surveillance of acute flaccid paralysis is crucial to detect poliovirus transmission, although complete global eradication has been hampered by several factors in endemic regions, including warfare, terrorism, and inadequate laboratory and environmental surveillance infrastructure. Globally, we are ill prepared to manage major pandemics and our health-care systems are fragile. Since the long-term complications of these infections are largely neurological, policy makers need to take a leadership role in curtailing infections and developing a pandemic preparedness for any future ones.
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