System Opportunistic Infections Research Articles

Characteristics of HIV-associated cryptococcal meningitis in a tertiary Chilean hospital: An observational retrospective study

BackgroundCentral nervous system opportunistic infections can be the first presentation of an HIV infection. Our aim is to describe clinical and laboratory characteristics of HIV-associated Cryptococcal Meningitis (CM), in-hospital outcomes and analyze associations of these parameters with adverse outcomes. MethodsObservational study of local cohort of HIV-associated cryptococcal meningitis in a high complexity tertiary urban hospital in Santiago, Chile.Descriptive analysis through chart review of all episodes of HIV-associated CM in adults, from 1995 to 2019.Inclusion criteria were confirmed CM with cerebrospinal fluid culture or India ink in the appropriate clinical context and HIV diagnosis. We selected relevant variables that have been described as predictors of adverse outcomes in the literature and explore associations in our cohort. ResultsThere were 37 HIV associated CM cases, occurring from 2000 to 2019. Majority were men (86 %) with a median age of 35 years. CM was the first HIV manifestation in 32 %. Opening pressure was measured in 10 % of patients at admission. Most CSF parameters were mildly altered, and two patients presented with completely normal CSF findings. Most patients −94,4 %- suffered adverse events secondary to antifungal therapy. Despite of recommendations against their use, steroids were frequently prescribed. Mortality was 18,9 %, and was associated with older age, and more days of headache prior to admission. ConclusionsCM clinical presentation and CSF characteristics are variable at presentation, which can lead to delayed diagnosis. Inappropriate use of corticosteroids, antifungal toxicity and suboptimal management of elevated intracranial pressure are key aspects to improve.

Long-term outcomes after new onset seizure in children living with HIV: A cohort study.

To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

Successful Liver Retransplantation in a Patient With Disseminated Aspergillosis and Nocardiosis: A Case Report

Clinical guidelines list active fungal infection and sepsis as contraindications to liver transplantation due to the risk of worsening infection with immunosuppression postoperatively. Mortality from systemic opportunistic infections in transplant recipients is high, approaching 100% for disseminated aspergillosis. However, the optimal duration of treatment required before transplant is unclear. Additionally, delaying surgery while the infection is treated risks death from hepatic decompensation and physical deconditioning, preventing progression to transplantation. Here, we present a patient who underwent successful repeat liver transplantation for recurrent autoimmune hepatitis and graft rejection while undergoing treatment for disseminated aspergillosis and nocardiosis. He had pulmonary, hepatic, and central nervous system involvement. He had received 2 months of antimicrobials but had ongoing radiologic evidence of infection when listed for retransplantation. He remains well and infection-free 1 year postoperatively. Few cases of successful liver transplantation in the setting of disseminated aspergillosis have been reported previously. To our knowledge, this is the first successful liver transplant in a patient with disseminated nocardial infection.

Single centre retrospective analysis of extracorporeal photopheresis (ECP) therapy in patients heavily pre-treated for chronic graft-versus-host disease (cGvHD) with steroid failure

BackgroundExtracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection. MethodsWe evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes. ResultsWith a median follow-up of 72 months, a gradual increase in ORR was noted over time: 21% (16 out of 75 patients), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. Gradual increase in CB was also observed over time with CB rate of 23% (17/75), 62% (39/63), and 76% (35/46) at months 3, 6 and 12, respectively. A total of 27 failures (36%) were noted, due to: 1) ECP resistance requiring switch to other therapy (n = 14, 19%), 2) non-relapse mortality (n = 10, 13%), 3) relapse of primary disease (n = 1, 1%) or 4) ECP procedure-related complication (n = 1, 1%, line infection), with 20 deaths (27%) observed. Failure-free survival (FFS) and overall survival (OS) rates were 68.3% and 85.9% at 12 months, respectively. After starting ECP, the proportions of patients who completely discontinued steroids were 17%, 32%, and 64% at months 3, 6 and 12, respectively. ConclusionECP is an effective treatment option for heavily pre-treated cGvHD patients.

Characterisation and variables associated with mortality in a population with HIV and central nervous system opportunistic infections in a Colombian public hospital in Bogotá

IntroductionHIV-associated mortality after a central nervous system opportunistic infection can reach up to 78%. In populations with limited economic resources, few studies have evaluated the clinical outcomes of these infections in patients with HIV. MethodsWe performed an observational analytical study using our hospital's database. Sociodemographic, clinical, and paraclinical data were gathered from patients with HIV-associated opportunistic neurological infections attended between January 2019 and January 2021. The aim of the study was to describe the in-hospital mortality rate and to establish associations with sociodemographic, clinical, and paraclinical variables. ResultsSeventy-five patients were included, with a mean age of 38.7 years. Fourteen (31.8%) were receiving antiretroviral therapy at the time of admission. The most frequent neurological infections were cerebral toxoplasmosis (37.3%, n = 28), meningeal cryptococcosis (20%, n = 15), and neurosyphilis (20%, n = 15). The in-hospital mortality rate was 25.3% (n = 19). The variables associated with increased mortality risk were diagnosis of meningeal cryptococcosis, admission to the ICU, and presence of fever. The variables associated with decreased mortality risk were CSF/blood glucose ratio > 0.5 and normal body mass index (18–25). ConclusionsIn a population of patients with HIV-associated opportunistic neurological infections, in-hospital mortality was 25.3%. The diagnosis of meningeal cryptococcosis, admission to the ICU, and the presence of fever are associated with higher mortality risk. To the contrary, CSF/blood glucose ratio > 0.5 and normal body mass index are associated with lower mortality risk.

An overview of opportunistic fungal infections associated with COVID-19.

The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera Candida, Aspergillus, and Mucor. There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.

Metagenomic next-generation sequencing versus traditional laboratory methods for the diagnosis of central nervous system opportunistic infections in HIV-infected Chinese adults

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods (X2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X2 = 4.601, P = 0.032; 8/12 vs 5/23, X2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.

Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: Results from a phase 2, randomized, double-blind, placebo-controlled study

Introduction: Tyrosine kinase 2 (TYK2) mediates signaling of Type I interferons and IL-23, key cytokines involved in systemic lupus erythematosus (SLE) pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for the treatment of adults with plaque psoriasis. This analysis assessed the efficacy and safety of deucravacitinib in patients with active SLE.&#x0D; Methods: This 48-week, double-blind, phase 2 trial (NCT03252587) randomized patients 1:1:1:1 to deucravacitinib (3 mg BID, 6 mg BID, 12 mg QD) or placebo. Oral corticosteroid tapering was required from weeks 8-20; further tapering was optional from weeks 32-40. The primary endpoint was the proportion of patients achieving SLE Responder Index-4 (SRI[4]) at week 32. Key secondary endpoints at week 48 included percentage of patients achieving SRI(4) and decrease of ≥50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50), in patients with baseline CLASI ≥10. Change from baseline in CLASI Activity Score (CLASI-A) over time was also assessed.&#x0D; Results: Of 363 randomized patients, 275 (76%) completed 48 weeks of treatment. Baseline demographic and disease characteristics were balanced across treatment groups, with baseline mean CLASI-A scores ranging from 8.0 to 8.6. The primary endpoint at week 32 was met, with significantly greater proportions of patients in deucravacitinib 3 mg BID and 6 mg BID groups vs placebo achieving SRI(4) responses (placebo: 34.4%; deucravacitinib 3 mg BID: 58.2%, P=0.0006; 6 mg BID: 49.5%, P=0.021; 12 mg QD: 44.9%, P=0.078). Patients treated with deucravacitinib demonstrated improvement across all secondary endpoints compared with placebo. In patients with CLASI ≥10 at baseline, greater mean changes from baseline in CLASI-A were observed in deucravacitinib vs placebo over 48 weeks of treatment (placebo: 16.7%; deucravacitinib 3 mg BID: 69.6%, P=0.0006; 6 mg BID: 56.0%, P=0.0058; 12 mg QD: 62.1%, P=0.0009). Rates of adverse events (AEs), serious AEs, and AEs of interest were similar between deucravacitinib and placebo groups. Most common AEs with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. No deaths, major adverse cardiac events, thrombotic events, systemic opportunistic infections, or active tuberculosis occurred.&#x0D; Conclusion: Deucravacitinib demonstrated sustained, meaningful clinical efficacy in SRI(4), improvement in mucocutaneous activity as measured by CLASI-A responses, and was well tolerated in patients with active SLE up to 48 weeks.

Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities

Vascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves must be confirmed. The immunosuppressive drug, tacrolimus, has been reported to promote nerve recovery in animal models. However, its repeated dosing comes with risks of systemic malignancies and opportunistic infections. Therefore, drug delivery approaches for locally sustained release can be designed to overcome this issue and reduce systemic complications. We developed a mixed thermosensitive hydrogel (poloxamer (PLX)-poly(l-alanine-lysine with Pluronic F-127) for the time-dependent sustained release of tacrolimus in our previous study. In this study, we demonstrated that the hydrogel drug degraded in a sustained manner and locally released tacrolimus in mice over one month without affecting the systemic immunity. The hydrogel drug significantly improved the functional recovery of injured sciatic nerves as assessed using five-toe spread and video gait analysis. Neuroregeneration was validated in hydrogel-drug-treated mice using axonal analysis. The hydrogel drug did not cause adverse effects in the mouse model during long-term follow-up. The local injection of encapsulated-tacrolimus mixed thermosensitive hydrogel accelerated peripheral nerve recovery without systemic adverse effects.

Presynaptic Hemiparkinsonism Following Cerebral Toxoplasmosis: Case Report and Literature Review.

Cerebral toxoplasmosis (CTx) is a central nervous system opportunistic infection with variable neurological manifestations. Although tropism of Toxoplasma gondii for the basal ganglia is well known, movement disorders (MDs) represent only a small percentage of CTx-related neurological complications. CTx-associated MDs are usually hyperkinetic, whereas parkinsonism associated with evidence of presynaptic dopaminergic deficit has never been described. We report a human immunodeficiency virus-positive patient who developed a complex MD featuring unilateral tremor combined with parkinsonism and dystonia following an acute episode of disseminated CTx. Her dopamine transporter scan (DaTscan) documented contralateral presynaptic dopaminergic deficit. Levodopa initiation improved both tremor and parkinsonism after ineffective trials of several other medications over the years. A total of 64 patients presenting with CTx-related MDs have been described. The most common MD was chorea (44%), followed by ataxia (20%), parkinsonism (16%), tremor (14%), dystonia (14%), myoclonus (3%), and akathisia (2%). DaTscan was performed only in 1 case, of Holmes tremor, that demonstrated reduced presynaptic dopaminergic uptake. Positive response to dopaminergic treatment was reported in 3 cases of Holmes tremor and 2 cases of parkinsonism. Presynaptic dopaminergic deficit may occur in CTx-related tremor combined with parkinsonism. Its identification should prompt initiation of levodopa, thus avoiding unnecessary trials of other drugs.

Immunosuppressants in Behcet’s disease: a boon or a bane?

Adalimumab is a disease-modifying antirheumatic drug and monoclonal antibody that works by antagonising tumour necrosis factor-alpha prescribed in many rheumatological conditions like Rheumatic arthritis, Ankylosing spondylitis and Behcet’s disease. Serious side effects with this drug include heart and liver failure, nervous and blood disorders, allergic and immune system reactions and opportunistic infections. A 27-year-old female patient, known case of Behcet’s disease presented to the hospital with complaints of fever, cough and breathlessness following administration of Adalimumab, six doses over three months. Chest X-ray and BAL-CBNAAT was suggestive of Tuberculosis. AKT was started and Adalimumab was suspended until patient recover.

LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Progressive Worsening of Neurological Manifestations in HIV-Associated Opportunistic Central Nervous System (CNS) Infection Patients After COVID-19 Vaccinations: A Possible Co-Incidence Causality

Case series Patients: Male, 23-year-old • Male, 23-year-old Final Diagnosis: Cerebral toxoplasmosis • HIV infection • pneumonia • pulmonary tuberculosis Symptoms: Fever • headache • hemiparesis • seizure • somnolence Medication: — Clinical Procedure: — Specialty: General and Internal Medicine • Neurology • Tropical Medicine Objective: Unusual clinical course Background:The iceberg phenomenon (in which the most of a problem is invisible) of people living with HIV/AIDS, particularly those with unknown HIV status, has been epidemiologically challenging. Central nervous system (CNS) opportunistic infections in patients with HIV/AIDS are one of the leading causes of morbidity and mortality in people living with HIV/AIDS. There are currently limited data on the immunogenicity, safety, and efficacy of COVID-19 vaccines in people living with HIV/AIDS with its associated opportunistic CNS infections as well as those without antiretroviral treatment.Case Reports:Two young men with previously unknown HIV status and its related opportunistic infections received their first doses of COVID-19 vaccine (Vero Cell), inactivated. Both patients had the risk factor of having sex with men (men who have sex with men). Fever and first neurological symptoms occurred within the first few days after vaccination. Both patients were hospitalized and were tested positive for HIV for the first time. Both were further diagnosed from brain imaging as having CNS opportunistic infections. A presumptive diagnosis of cerebral toxoplasmosis was established as the working diagnosis according to the laboratory and epidemiological factors. Despite the treatment, neurological and clinical deficits worsened and eventually led to death in both patients.Conclusions:The causality analyses showed that both adverse events had a possible inconsistent causal relationship to COVID-19 vaccination. Our cases may reflect the need for further studies on the safety of COVID-19 vaccines in people with HIV/AIDS-associated CNS opportunistic infection as well as people with HIV/AIDS who never receive antiretroviral treatment (ART).

Progressive multifocal leukoencephalopathy after daratumumab in multiple myeloma: A case report

Progressive multifocal leukoencephalopathy (PML) is a rare severe central nervous system (CNS) opportunistic infection usually occurring in immunocompromised patients. Iatrogenic PML has been described in patients assuming treatment suppressing immune surveillance in CNS. Daratumumab is an anti-CD38 monoclonal antibody, used to treat Multiple Myeloma (MM), causing the destruction of suppressive cells and the increase of CD4+ helper and CD8+ cytotoxic T cells. Only two cases of PML on daratumumab has been reported in literature.

Seizure in HIV-infected patients: clinical presentation, cause and treatment outcome in Ethiopia\u2014a retrospective study

BackgroundThe estimated number of adult patients living with HIV infection in Ethiopia in 2012 was approximately 800,000. Seizure occurs in 2 to 3% and 6.1% to 34.3% in patients with HIV infection and patients with neurological complications of HIV infection, respectively. Studies on HIV infection and seizure are rare in Ethiopia. The purpose of this study was to assess clinical presentation, cause and treatment outcome of patients with HIV infection presented with seizure.MethodsIn this retrospective study, patients aged ≥ 13 years with HIV infection presented with seizure were included. Medical records were reviewed and demographic and clinical data were collected.ResultsRecords of 146 patients were analysed. Males were 55.5% and the mean age was 34 years. The diagnosis of HIV infection was made after current hospital admission in 69% of patients. Almost all patients (98.6%) had stage 4 HIV infection with very low CD4 count (mean = 77/mm3). In almost all patients seizure was a recent onset at current admission; either it started after admission (42.5%) or within 3 months prior to admission (52.5%). The types of seizures were: generalized tonic–clonic seizure [GTCS] (69.2%), focal motor with secondarily generalization [FMWSG] (19.9%) and simple focal motor (11%). The common causes of seizure were: cerebral toxoplasmosis (46%), tuberculous meningitis (35.6%) and cryptococcal meningitis (13.7%). Case-fatality was 53% and predictors of mortality were: seizure started after admission, change in mentation and comatose at initial evaluation.ConclusionsMost patients had stage 4 HIV infection with very low CD4 count and a recent onset seizure which started within 3 months at initial evaluation. GTCS was the commonest seizure type and most causes of seizure were central nervous system opportunistic infections. The case-fatality was high and change in sensorium was an independent predictor of mortality. To prevent the high mortality and morbidity prevention of HIV infection, early diagnosis and treatment, improving diagnostic facilities and access to non-enzyme inducing antiepileptic drugs are recommended.

Blood-Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers.

Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies.

Myelin basic protein and its diagnostic value in HIV-infected individuals with 4th clinical stage and neuroinfections

It was shown that in HIV-infected patients, pathomorphological changes in the white matter in the form of demyelinization are already observed in the early stages of the disease. The most studied marker of this process is myelin basic protein that can be detected in cerebrospinal fluid or serum immediately after acute myelin breakdown.&#x0D; The aim. To assess the diagnostic value of myelin basic protein content in serum and cerebrospinal fluid of HIV-infected individuals with 4th clinical stage and central nervous system opportunistic infections.&#x0D; Materials and methods. Using ELISA with diagnostic kit “MBP ELISA” (Ansh Labs, USA), we studied the myelin basic protein content in serum and cerebrospinal fluid of 53 HIV-infected patients with 4th clinical stage and central nervous system opportunistic infections depending on its etiology, the outcome of the diseases and according to Glasgow coma scale score. As well correlation analysis with some laboratory and clinical indicators was performed.&#x0D; Results. We found significantly increased myelin basic protein content in both cerebrospinal fluid and serum of HIV-infected patients 4th clinical stage with central nervous system opportunistic infections compared to control (p˂0.01), which indicate the presence of active demyelinization in central nervous system. The highest cerebrospinal fluid myelin basic protein was registered in patients with an unfavourable outcome of the disease, as death or residual neurologic deficit, and patients with cerebral toxoplasmosis. The cerebrospinal fluid myelin basic protein had an association with the size of white matter lesions on magnetic resonance imaging and serum myelin basic protein content.&#x0D; Conclusions. Myelin basic protein detection in cerebrospinal fluid as well as in serum can serve as an additional quantitative marker of myelin disruption, which can be used along with magnetic resonance imaging for the diagnosis improvement and prognosis of central nervous system opportunistic infections in HIV-infected individuals with 4th clinical stage

The clinical characteristics and outcome of cryptococcal meningitis with AIDS in a tertiary hospital in China: an observational cohort study

BackgroundDespite the profound impact of antiretroviral therapy in the control of AIDS mortality, central nervous system opportunistic infections remains a significant burden in AIDS patients. This retrospective study aims to elucidate the clinical characteristics, outcome and risk factors of cryptococcal meningitis (CM) poor prognosis in AIDS patients from a tertiary hospital in China.MethodsClinical data from 128 patients admitted in Beijing Ditan Hospital, Capital Medical University from November 2008 to November 2017 was collected. The cohort was stratified based on treatment outcome (effective 79%, and ineffective 21%), and Multivariate Logistic regression analysis used to identify risk factors of poor disease prognosis.ResultsAge, incidence of cerebral infarction, the proportion of consciousness disorder, and fasting plasma glucose was higher in the ineffective treatment group than the effective treatment group. The duration of treatment in the induction period of the ineffective group was significantly shorter than that of the effective group. Multivariate Logistic regression analysis indicated that the occurrence of cerebral hernia and consciousness disorder were risk factors for the prognosis of AIDS patients with CM infection, while the duration of treatment in the induction period was a indicative of a better prognosis in AIDS with CM infection complications. Finally, shunt decompression therapy correlated with a better disease outcome.ConclusionsThis retrospective study exposes the main risk factors associated with worse disease prognosis in AIDS patients with CM infection complications.

Differential Effects of AIDS and Chronic Human Immunodeficiency Virus Infection on Gray Matter Volume.

Age, human immunodeficiency virus (HIV) infection, illicit drug use, and central nervous system (CNS) opportunistic infections can affect brain structure, with the striatum being particularly sensitive to HIV effects. Nevertheless, the impact of non-CNS AIDS-defining illness (ADI) on brain structure has been less investigated. We examined ADI and HIV effects on brain volume. In a cross-sectional study, including 95 virally suppressed seropositive and 84 demographically matched, seronegative participants, we examined serostatus and ADI effects. Cortical and subcortical gray matter volume (GMV) regions of interest were estimated with computational neuroanatomy techniques applied to high-resolution, T1-weighted magnetic resonance imaging data. Linear regression was used to model HIV serostatus and ADI effects on global and regional GMV, adjusting for age, sex, CD4 nadir, drug use, and total intracranial volume. While HIV serostatus was associated with lower striatal volume (B = -.59 [95% confidence interval {CI}, -1.08 to -.10]), co-occurring ADI was independently associated with lower striatal volume (B = -.73 [95% CI, -1.36 to -.09]). ADI was also associated with lower global (B = -19.35 [95% CI, -32.42 to -6.29]) and regional GMV. While HIV infection is associated with a localized effect on striatal structure, having a prior ADI is a strong predictor of smaller global and regional GMV. The lack of interaction between HIV serostatus or ADI with age suggests that chronic HIV infection and ADI have independent effects on brain structure, without associated accelerated lower volume with age. ADI history should be incorporated into statistical adjustments in HIV neuroimaging analysis. These findings also lend support to current HIV treatment guidelines urging prompt antiretroviral therapy initiation after HIV diagnosis.

Ventriculoperitoneal shunt insertion in human immunodeficiency virus infected adults: a systematic review and meta-analysis

BackgroundHydrocephalus is a common, life threatening complication of human immunodeficiency virus (HIV)-related central nervous system opportunistic infection which can be treated by insertion of a ventriculoperitoneal shunt (VPS). In HIV-infected patients there is concern that VPS might be associated with unacceptably high mortality. To identify prognostic indicators, we aimed to compare survival and clinical outcome following VPS placement between all studied causes of hydrocephalus in HIV infected patients.MethodsThe following electronic databases were searched: The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE, CINAHL Plus, LILACS, Research Registry, the metaRegister of Controlled Trials, ClinicalTrials.gov, African Journals Online, and the OpenGrey database. We included observational studies of HIV-infected patients treated with VPS which reported of survival or clinical outcome. Data was extracted using standardised proformas. Risk of bias was assessed using validated domain-based tools.ResultsSeven Hunderd twenty-three unique study records were screened. Nine observational studies were included. Three included a total of 75 patients with tuberculous meningitis (TBM) and six included a total of 49 patients with cryptococcal meningitis (CM). All of the CM and two of the TBM studies were of weak quality. One of the TBM studies was of moderate quality. One-month mortality ranged from 62.5–100% for CM and 33.3–61.9% for TBM. These pooled data were of low to very-low quality and was inadequate to support meta-analysis between aetiologies. Pooling of results from two studies with a total of 77 participants indicated that HIV-infected patients with TBM had higher risk of one-month mortality compared with HIV non-infected controls (odds ratio 3.03; 95% confidence-interval 1.13–8.12; p = 0.03).ConclusionsThe evidence base is currently inadequate to inform prognostication in VPS insertion in HIV-infected patients. A population-based prospective cohort study is required to address this, in the first instance.