Exploring Microorganisms Associated to Acute Febrile Illness and Severe Neurological Disorders of Unknown Origin: A Nanopore Metagenomics Approach.

Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical cases. In this study, we aim to shed light on the etiological agents underlying AFI and SND cases that conventional diagnostic methods have not been able to fully elucidate. Our approach involved analyzing samples from fourteen hospitalized patients using a comprehensive nanopore metagenomic approach. This process included RNA extraction and enrichment using the SMART-9N protocol, followed by nanopore sequencing. Subsequent steps involved quality control, host DNA/cDNA removal, de novo genome assembly, and taxonomic classification. Our findings in AFI cases revealed a spectrum of disease-associated microbes, including Escherichia coli, Streptococcus sp., Human Immunodeficiency Virus 1 (Subtype B), and Human Pegivirus. Similarly, SND cases revealed the presence of pathogens such as Escherichia coli, Clostridium sp., and Dengue virus type 2 (Genotype-II lineage). This study employed a metagenomic analysis method, demonstrating its efficiency and adaptability in pathogen identification. Our investigation successfully identified pathogens likely associated with AFI and SNDs, underscoring the feasibility of retrieving near-complete genomes from RNA viruses. These findings offer promising prospects for advancing our understanding and control of infectious diseases, by facilitating detailed genomic analysis which is critical for developing targeted interventions and therapeutic strategies.

Long term neurologic sequelae in a Mexican rocky mountain spotted fever case.

During the second half of the twentieth century, neurologic sequelae associated with central nervous system impairment caused by Rickettsia rickettsii were studied widely and exclusively in the United States. We present the case of a Mexican pediatric patient with neurologic sequelae 10 years after an acute infection by R. rickettsii.

Long term neurologic sequelae in a Mexican rocky mountain spotted fever case

ABSTRACT During the second half of the twentieth century, neurologic sequelae associated with central nervous system impairment caused by Rickettsia rickettsii were studied widely and exclusively in the United States. We present the case of a Mexican pediatric patient with neurologic sequelae 10 years after an acute infection by R. rickettsii.

Neurotuberculosis in cattle in southern Brazil.

Tuberculosis in cattle is a chronic infectious-contagious disease characterized by the development of nodular lesions (granulomas) in mainly the lungs and regional lymph nodes. It is caused by Mycobacterium tuberculosis complex, an acid-fast bacillus (AFB). Tuberculosis in the central nervous system is a rare condition in cattle. Herein, we describe the clinical and pathological findings of six neurotuberculosis cases in cattle diagnosed in Southern Brazil. The average age of the cattle affected was 12 months, and they varied in breed and sex. The clinical history ranged from 5 to 30 days and was characterized by motor incoordination, opisthotonus, blindness, and progression to recumbency. The cattle were euthanized, and grossly, the leptomeninges at the basilar brain showed marked and diffuse expansion, with nodular yellowish lesions ranging in size. On microscopic examination, there were multifocal granulomas located mainly in the meninges, though sometimes extending to adjacent neuropil or existing as isolated granulomas in neuropil. AFBs were observed in the cytoplasm of epithelioid macrophages and multinucleated giant cells through Ziehl-Neelsen histochemical staining and identified as Mycobacterium sp. through immunohistochemistry.

Quantitation of cerebrospinal fluid lactic acid in infectious and non-infectious neurological diseases.

BACKGROUND: The differential diagnosis between bacterial and viral meningitis is not easy in some cases. Cerebrospinal fluid (CSF) analysis is essential for establishing this diagnosis. The objectives were to quantitate lactic acid (LA) concentrations in bacterial and viral meningitis, and other central nervous system (CNS) diseases in order to evaluate the diagnostic utility of CSF LA for discriminating bacterial from viral meningitis. METHODS: CSF LA was measured in 139 CSF samples from seven groups: viral meningitis with classic CSF; suspicion of viral meningitis with neutrophils in CSF; bacterial meningitis; non-infectious neurological diseases; chronic meningitis; traumatic lumbar puncture (LP) and normal CSF. RESULTS: CSF LA was higher in bacterial meningitis 8.7 + 5.4 mmol/L compared with viral meningitis (1.9 + 0.6) and the other groups (p < 0.0001). CSF LA in the groups with viral meningitis was not different compared to groups with non-infectious CNS diseases and chronic meningitis. The ability of CSF LA to discriminate bacterial from viral meningitis showed a sensitivity of 80% and specificity of 97%, positive predictive value (PPV) of 94%, and negative predictive value (NPV) of 89%. CONCLUSIONS: CSF LA is a powerful test to discriminate bacterial from viral meningitis with high sensitivity, specificity and predictive values. CSF LA can help in the cases with diagnostic uncertainty.

Highly active antiretroviral therapy access and neurological complications of human immunodeficiency virus infection: impact versus resources in Brazil.

Currently, there are almost 600,000 human immunodeficiency virus (HIV)-infected individuals in Brazil. From 1984 to 2004, 362,364 acquired immunodeficiency virus (AIDS) cases were officially reported and 155,000 patients are under highly active antiretroviral therapy (HAART) treatment. Like in developed countries, universal access to treatment in Brazil has definitively changed both mortality and morbidity of AIDS. Today, the median survival time is 58 months, with a 2-year survival of 63%, versus 18 months before HAART. As expected, the incidence of nervous system opportunistic infectious diseases and tumors has also decreased in Brazil. However, few Brazilian reports about neurological manifestations of HIV infection are available, particularly after the beginning of more effective antiretroviral therapy. Autopsy series report that toxoplasmosis is the most prevalent neurological disease, followed by cryptococcosis and HIV encephalitis. A much lower incidence of progressive multifocal leukoencephalopathy has been described in Brazil than in reports from developed countries. A possibility for this discrepancy could be differences in terms of JC virus (JCV) isolates or even the interactions between JCV and local HIV strains. Some particularities about the involvement of the nervous system in Brazilian patients are worthy of note, such as the occurrence of central nervous system involvement in chronic Chagas' disease in patients with AIDS, and the concomitance of leprosy and HIV infection. National surveillance of neurological manifestations of HIV infection is needed to ascertain the real impact of HAART on nervous system diseases associated with AIDS in Brazil.

Cuadro clínico, criterios diagnósticos y complicaciones / Clinical picture, diagnostic criteria and complications

El diagnóstico de EI comienza con una cuidadosa historia y examen físico. El antecedente de endocarditis previa, valvulopatías previas (lesiones congénitas o adquiridas), manipulaciones dentales, genitourinarias, broncoscopias, drogadicción endovenosa o tatuajes en la piel, deben orientar a la puerta de entrada y bacteremia consecutiva. El diagnóstico puede basarse en la presencia de manifestaciones cardíacas o sistémicas. La presencia de un soplo cardíaco, reciente o que haya variado, asociado a fiebre, debe hacerse sospechar el diagnóstico, especialmente si existe una válvula protésica. Los criterios diagnósticos de Duke han sido un aporte para el diagnóstico de esta afección y para un manejo más oportuno y precoz de ella. Las complicaciones en la EI pueden afectar a cualquier órgano. Las complicaciones cardíacas son frecuentes y la insuficiencia cardíaca puede acarrear la muerte. La formación de abscesos intracardíacos con alteraciones en la conducción, pueden afectar el miocardio y pericardio, siendo necesaria la resolución quirúrgica. Las complicaciones extracardíacas, neurológicas, vasculares, renales y sépticas son comunes y habitualmente producidas por embolización de vegetaciones o complejos inmunes. A pesar de los avances en la detección y tratamiento de estas complicaciones, el manejo de este cuadro y su diagnóstico diferencial persiste difícil y es de alta letalidad.

Criptococosis del sistema nerviosos central. Estudio de 32 casos 1975-1991

Este es el segundo estudio sobre criptococosis del sistema nervioso central (SNC) realizado en el Centro Hospitalario San Juan de Dios de Bogotá; corresponde al período 1975 -1991 y comprende 32 casos. LLama la atención en este período el aumento de la referencia de esta enfermedad en esta institución en los últimos tres años y su asociación con el SIDA (cinco casos). Los principales síntomas y signos observados fueron : cefale (26/32), alteraciones de conciencia (23/32), náuseas y vómito (19/32), signos meníngeos (18/32), fiebre (14/32) y papiledema (15/32). E diagnóstico se confirmó por uno a varios de los siguientes estudios : examen directo del LCR (tinta china) positivo en 75 por ciento, cultivo positivo del LCR en 96 por ciento, aglutinación de látex positiva en LCR en 90 por ciento, aglutinación de látex positiva en suero en 72 por ciento y hallazgos histopatológicos demostrativos de la criptococosis a nivel del SNC en nueve casos de autopsia. Se analizan la alta mortalidad (21/32 casos) y las dificultades del tratamiento.

[Neurologic manifestations in pediatric patients with AIDS]. / Manifestaciones neurológicas en pacientes pediátricos con síndrome de inmunodeficiencia adquirida.

Since the first cases of childhood AIDS were reported, the neurological involvement has been more frequently recognized. Several motor, intellectual and conductual changes as well as unexplained abnormalities have been described due to CNS infections. Findings have shown HIV to affect the CNS although it is unknown as to when the viral invasion actually occurs. This report describes the neurological manifestations found in pediatric patients with HIV infection at the Hospital Infantil de Mexico and their correlations with CT scans, EEGs, auditory evoked potentials, I.Q.s and postmortem findings. The medical records of 60 symptomatic HIV infected children, stages P0 to P2, are reviewed. Neurological abnormalities were found in 51 patients, 20 of which (39.2%) were due to perinatal infection with symptoms starting, on the average at 11 months 7 days (from the initial contact) taking into consideration in utero exposure. Nine cases (17.6%) were patients infected through transfusions with symptoms appearing on the average at 24 months 8 days; 2 cases (3.9%) were of unknown origin. The CT scans, EEGs and psychometric evaluations of the HIV infected patients correlated well with the clinical findings.

[HTLV-I retrovirus in Chile: study on 140 neurological patients]. / Retrovirus HTLV-1 en Chile: estudio en 140 enfermos neurológicos.

We screened 140 patients with different neurological diseases for the presence of anti HTLV-1 virus antibodies. ELISA test confirmed with Western Blot analysis was performed in CSF and blood. Positive findings were obtained in 23 out of 52 patients with progressive spastic paraparesis (44%). All patients with multiple sclerosis, polymyositis, amyotrophic lateral sclerosis or chronic polyneuropathy were negative. Patients with progressive spastic paraparesis and positive HTLV-1 antibodies were most commonly women (78%) and middle aged (mean 46 years old), with a history of surgical interventions (70%) or blood transfusion (35%). A slowly progressive spastic paraparesis with asymmetric onset and minimal sensory complaints was observed in some cases. Mononuclear pleocytosis in the CSF was observed in 35% with an increased IgG index in 88%. A delayed latency and low amplitude of somatosensory evoked potentials was observed in 89% of patients.

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders.

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome.

[Clinical characteristics of various neuroviroses in relation to their etiology]. / Características clínicas de algunas neurovirosis en relación con su etiología

No clinical, cytochemical nor electroencephalographic standards of behavior, specific for each etiology were found in a series of 67 cases of viral infection of the nervous system; however, the severeness was greater in cases of infectious mononucleosis with encephalic involvement and in cases caused by Coxsackie B5 possibly because these appeared in younger patients. The group with greater percentage of definitive motor and intellectual sequelae was found in cases with infectious mononucleosis and ECHO. Cases due to herpes simplex were not more severe during the acute stage, but followed a course with an important percentage of definitive sequelae. Meningoencephalitides from parotiditis were milder, and only in one case did they show permanent motor sequelae.