RESUMEN
Herpes zoster (HZ), commonly known as shingles, is a painful blistering rash in dermatomal distribution, caused by the reactivation of varicella-zoster virus (VZV) that was acquired during a primary varicella infection. While commonly afflicting adults, cases of HZ in paediatric patients are infrequently reported. Such cases are predominantly reported in children who have had prior exposure to VZV, either during pregnancy, early childhood or have been vaccinated with live attenuated VZV. This report presents the first known case to our knowledge of HZ as the initial manifestation of a VZV infection in an immunocompetent toddler in the UK. The report details the chronology of the infection event and discusses the clinical context behind HZ presentations in paediatrics globally. It provides a compelling illustration of the uncommon presentation of VZV infection in an immunocompetent child devoid of antecedent virus exposure, thus meriting acknowledgement and potentially further investigation as to the cause.
Asunto(s)
Herpes Zóster , Herpesvirus Humano 3 , Humanos , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3/aislamiento & purificación , Antivirales/uso terapéutico , Aciclovir/uso terapéutico , Lactante , Masculino , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Femenino , PreescolarRESUMEN
The patient, a 36-year-old female, had no previous history of shingles. She was admitted to the hospital due to nausea and lightheadedness. Upon admission, she was diagnosed with bilateral medial medullary infarcts. She received treatment with intravenous edaravone and argatroban, as well as antiplatelet therapy with aspirin and clopidogrel. However, her dysphagia, dysarthria, and paraplegia worsened. Due to changes in the lesion of the basilar artery on brain |MRA, we suspected the possibility of basilar artery dissection, and discontinued antiplatelet therapy. Subsequent imaging studies suggested vasculitis. After examining the cerebrospinal fluid, we diagnosed varicella-zoster virus (VZV) vasculopathy. Based on this diagnosis, we administered steroid pulse therapy for three days, started intravenous acyclovir, and resumed antithrombotic therapy with clopidogrel. Prednisone was administered for five days. Biochemical tests revealed an elevated D-dimer level. Due to the presence of lower extremity venous thrombus, clopidogrel was replaced with apixaban. The acyclovir infusion was discontinued due to observed acyclovir-induced neutropenia. These treatments improved neurological symptoms, circumflex thickening of the basilar artery, and contrast effects in the same area. On the 70th day, the patient was transferred to the hospital for rehabilitation. It is important to consider VZV angiopathy as a potential cause of juvenile cerebral infarction accompanying progressive basilar artery stenosis, regardless of the presence or absence of a skin rash.
Asunto(s)
Herpesvirus Humano 3 , Humanos , Femenino , Adulto , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/diagnóstico , Aciclovir/administración & dosificación , Quimioterapia por Pulso , Bulbo Raquídeo , Infartos del Tronco Encefálico/etiología , Infartos del Tronco Encefálico/tratamiento farmacológico , Antivirales/administración & dosificación , Resultado del Tratamiento , Clopidogrel/administración & dosificación , Piridonas/administración & dosificación , PirazolesAsunto(s)
Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Infección por el Virus de la Varicela-Zóster , Humanos , Embarazo , Femenino , Complicaciones Infecciosas del Embarazo/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Infección por el Virus de la Varicela-Zóster/prevención & control , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Herpesvirus Humano 3 , Varicela/prevención & control , Recién Nacido , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Visceral disseminated varicella zoster virus (VZV) infection is a rare but life-threatening complication in immunosuppressed patients. Herein, we report a survival case of visceral disseminated VZV infection in a patient with systemic lupus erythematosus (SLE). CASE PRESENTATION: A 37-year-old woman was diagnosed as SLE and initial induction therapy was started. Two months after starting the immunosuppressive therapy consisting of 40 mg of prednisolone (PSL) and 1500 mg of mycophenolate mofetil (MMF) daily, she suddenly developed strong abdominal pain, which was required opioid analgesics, followed by systemic skin blisters, which were diagnosed as varicella. Laboratory findings showed rapid exacerbation of severe liver failure, coagulation abnormalities and increased numbers of blood VZV deoxyribonucleic acid (DNA). Therefore, she was diagnosed as visceral disseminated VZV infection. Multidisciplinary treatment with acyclovir, immunoglobulin and antibiotics was started, the dose of PSL was reduced, and MMF was withdrawn. By their treatment, her symptoms were resolved and she finally discharged. CONCLUSIONS: Our case highlights the importance of a clinical suspicion of visceral disseminated VZV infections, and the necessity of immediate administration of acyclovir and reduced doses of immunosuppressant to save patients with SLE.
Asunto(s)
Varicela , Herpes Zóster , Lupus Eritematoso Sistémico , Infección por el Virus de la Varicela-Zóster , Humanos , Femenino , Adulto , Herpesvirus Humano 3/genética , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Aciclovir/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Prednisolona , Ácido Micofenólico/uso terapéuticoRESUMEN
In this case report, we describe two unusual presentations of varicella-zoster virus (VZV) reactivation without rash, a condition known as Zoster Sine Herpete (ZSH). In Case 1, a 58-year-old woman presented with severe right-sided chest pain under her breast that radiated to the ipsilateral back. After the initial workup ruled out cardiac and musculoskeletal etiologies, the characteristic dermatomal distribution of pain made us suspect VZV reactivation. A diagnosis of ZSH was made with positive VZV IgG and IgM serologies and symptomatic relief after famciclovir treatment. In Case 2, a 43-year-old woman presented with a severe headache and resolved sharp right flank pain. She was diagnosed with varicella meningitis after cerebrospinal fluid showed positive VZV DNA. Intravenous acyclovir treatment resulted in symptom resolution. The most common presentation of VZV reactivation is Herpes Zoster, or shingles, making ZSH a frequently missed diagnosis. High clinical suspicion is warranted to prevent life-threatening complications of ZSH.
Asunto(s)
Varicela , Herpes Zóster , Infección por el Virus de la Varicela-Zóster , Zoster Sine Herpete , Humanos , Femenino , Persona de Mediana Edad , Adulto , Zoster Sine Herpete/diagnóstico , Zoster Sine Herpete/tratamiento farmacológico , Varicela/complicaciones , Herpesvirus Humano 3 , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Dolor en el Pecho/complicaciones , Cefalea/etiologíaRESUMEN
Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunity. While diagnosis of more common HSV and/or VZV infections is frequently clinically based, immunocompromised hosts may have atypical skin presentation or visceral involvement. Thus, diagnostic confirmation using virus-specific tests such as polymerase chain reaction or immunohistochemical staining is crucial in some cases. Oral acyclovir, valacyclovir and famciclovir are usually used for mild to moderate infections and intravenous acyclovir is the drug of choice for severe or disseminated infections. Foscarnet can be used when acyclovir-resistance is confirmed or suspected. Pharmaceutical prophylaxis against HSV and/or VZV should be considered in high-risk cancers patients. Currently, there is no commercially available vaccine against HSV, but VZV vaccines are available to prevent varicella and zoster.
Asunto(s)
Varicela , Herpes Zóster , Neoplasias , Infección por el Virus de la Varicela-Zóster , Humanos , Herpesvirus Humano 3 , Simplexvirus , Calidad de Vida , Herpes Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Aciclovir , Neoplasias/complicacionesRESUMEN
Visceral disseminated varicella zoster virus infection (VD-VZV) is a rare complication in immunocompromised patients. Although systemic lupus erythematosus (SLE) patients have a higher risk of VZV infection, only a few reports describe VD-VZV in SLE. Here, we report a 48-year-old woman with SLE who had received maintenance therapy. She was transferred to the hospital because of severe epigastric pain. There were no significant abnormalities in abdominal computed tomography and upper gastrointestinal endoscopy. On hospital day 4, she developed vesicular eruption on her face and abdomen. VZV antigen was detected in specimens obtained from skin lesions, and treatment with acyclovir was started. VZV DNA in blood turned out to be positive, and the epigastric pain was thought to be caused by VD-VZV. There is a risk of VD-VZV in patients with SLE, even in those receiving non-intensive maintenance therapy.
Asunto(s)
Herpes Zóster , Lupus Eritematoso Sistémico , Infección por el Virus de la Varicela-Zóster , Femenino , Humanos , Persona de Mediana Edad , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3/genética , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Dolor/complicacionesRESUMEN
The triggering effect of herpes simplex virus infection on the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is now well established. However, there are very few reports that has linked a varicella zoster virus (VZV) reactivation with anti-NMDAR encephalitis. In this report, we describe a case of a 57-year-old man presented with atypical clinical presentation of anti-NMDAR encephalitis with gait ataxia, complete ophtalmoplegia, and abolished reflexes followed by drowsiness and confusion. Initial diagnosis of Bickerstaff's brainstem encephalitis was suspected. Few days later, the patient developed herpes zoster in a localized right T1-T2 dermatome. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for VZV was negative. CSF anti-NMDA antibodies were proved positive. A diagnosis of anti-NMDAR encephalitis with concomitant VZV skin reactivation was retained. Favorable outcome with combined antiviral treatment and immunomodulatory therapy was observed. Concomitant VZV reactivation with autoimmune encephalitis is possible. Prognosis and therapeutic options in this rare condition remain to be clarified.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Varicela , Herpes Zóster , Infección por el Virus de la Varicela-Zóster , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Herpes Zóster/diagnóstico , Herpesvirus Humano 3 , Humanos , Masculino , Persona de Mediana Edad , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoRESUMEN
ABSTRACT: We present a case of a 55-year-old man with a rash on his right foot that was biopsied and diagnosed as a Varicella Zoster virus infection with an accompanying positive immunohistochemical study with antiviral antibodies. He concomitantly suffered from a Varicella Zoster virus meningitis. The skin biopsies not only showed clear histologic signs of viral cytopathic effects but also showed intercellular IgG and C3 intraepidermal staining by direct immunofluorescence study, findings which are typically consistent with pemphigus vulgaris. However, the patient did not have any history of pemphigus; there was no mucosal involvement, and serum antibodies to desmoglein 1 and 3 were negative. After discharge, the patient continued to have right-sided foot pain, and he continued the acyclovir treatment.
Asunto(s)
Varicela , Herpes Zóster , Pénfigo , Infección por el Virus de la Varicela-Zóster , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Varicela/complicaciones , Herpes Zóster/complicaciones , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3 , Humanos , Masculino , Persona de Mediana Edad , Pénfigo/patología , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoRESUMEN
Varicella-zoster virus (VZV) can cause visceral disseminated VZV infection in immunocompromised patients. We experienced visceral disseminated VZV infection in an immunocompetent host. A 78-year-old woman visited our hospital complaining of abdominal pain that had persisted for 7 days. On day 3 after admission, a skin rash with blisters appeared mainly on her head and trunk that was diagnosed as generalized zoster via rapid skin VZV diagnostic kit. Esophagogastroduodenoscopy showed gastric erosions, and VZV was detected by real-time polymerase chain reaction testing of the gastric mucosal biopsy specimen. Computed tomography imaging also revealed pancreatitis and colitis, and she was diagnosed as having visceral disseminated VZV infection involving multiple organs. She was treated with acyclovir intravenously, after which her skin rash and abdominal pain disappeared. Because visceral disseminated VZV infection can occur in immunocompetent patients, this disease should be considered in patients with unexplained inflammatory lesions of the gastrointestinal tract or pancreas.
Asunto(s)
Exantema , Herpes Zóster , Infección por el Virus de la Varicela-Zóster , Dolor Abdominal/etiología , Anciano , Exantema/complicaciones , Femenino , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/etiología , Herpesvirus Humano 3 , Humanos , Huésped Inmunocomprometido , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoAsunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Infección por el Virus de la Varicela-Zóster , Vacunas contra la COVID-19/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/diagnóstico , Herpesvirus Humano 3 , Humanos , Trasplante de Células Madre/efectos adversos , Vacunación , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES. AIM OF THE STUDY: In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES. METHODS: and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells. RESULTS: To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1ß, IL-6, and TNF-α. CONCLUSION: E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.
Asunto(s)
Antivirales/farmacología , Elaeocarpaceae/química , Herpesvirus Humano 3/efectos de los fármacos , Extractos Vegetales/farmacología , Analgésicos/aislamiento & purificación , Analgésicos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antipiréticos/aislamiento & purificación , Antipiréticos/farmacología , Antivirales/aislamiento & purificación , Inflamación/tratamiento farmacológico , Inflamación/virología , Masculino , Ratones , Ratones Endogámicos ICR , Dolor/tratamiento farmacológico , Dolor/virología , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/virologíaRESUMEN
We herein report the case of a 78-year-old woman who was diagnosed as having disseminated herpes zoster (DHZ) complicated with probable varicella-zoster pneumonia during maintenance therapy for microscopic polyangiitis. Because the patient had severe renal dysfunction, amenamevir administration was started to avoid any neurotoxicity of acyclovir, which is suggested to be optimal for treatment. It ameliorated her symptoms without any adverse events. This is the first report suggesting the efficacy of amenamevir in the treatment of severe herpes zoster infection with coexisting DHZ and probable varicella-zoster pneumonia. Amenamevir could thus be a treatment option for severe varicella zoster virus infections.
Asunto(s)
Varicela , Herpes Zóster , Neumonía , Infección por el Virus de la Varicela-Zóster , Aciclovir/uso terapéutico , Anciano , Antivirales/efectos adversos , Varicela/inducido químicamente , Varicela/complicaciones , Varicela/tratamiento farmacológico , Femenino , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3 , Humanos , Huésped Inmunocomprometido , Oxadiazoles , Neumonía/complicaciones , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoRESUMEN
Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy.
Asunto(s)
Dermis/virología , Herpes Simple/virología , Herpesvirus Humano 1/patogenicidad , Herpesvirus Humano 2/patogenicidad , Herpesvirus Humano 3/patogenicidad , Células del Estroma/virología , Infección por el Virus de la Varicela-Zóster/virología , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , ADN Viral/genética , Dermis/efectos de los fármacos , Dermis/patología , Femenino , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/efectos de los fármacos , Herpesvirus Humano 2/genética , Herpesvirus Humano 3/efectos de los fármacos , Herpesvirus Humano 3/genética , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Células del Estroma/efectos de los fármacos , Células del Estroma/patología , Resultado del Tratamiento , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND Varicella zoster virus (VZV) infection causes 2 clinically distinct forms of the disease: varicella (chickenpox) and herpes zoster (shingles). Primary VZV infection results in the diffuse vesicular rash of varicella, or chickenpox. Endogenous reactivation of latent VZV typically results in a localized skin infection known as herpes zoster, or shingles. The infection usually manifests as a self-limited disease. However, it can be associated with various neurological complications such as encephalitis, meningitis, ventriculitis, cerebellar ataxia, ischemic or hemorrhagic, and, rarely, cerebral venous sinus thrombosis (CVST). This report presents a case of cerebral venous sinus thrombosis due to varicella zoster virus infection in a 20-year-old Nepalese man who presented to the Emergency Department with headache. CASE REPORT A 20-year-old Nepalese male patient presented to the Emergency Department with headache of 10 day's duration. Five days prior to that, he had a diffuse pruritic skin rash. Examination as well as serology confirmed the presence of primary varicella infection. Computed tomography (CT) and magnetic resonance venography (MRV) demonstrated CVST. Thrombophilia workup revealed a transient elevation of antiphospholipid serology. Shortly after admission, the patient had a transient seizure. He was treated with acyclovir, levetiracetam, and anticoagulation. A comprehensive literature review of similar cases was performed to establish a link between thrombotic complications and primary VZV infection and to formulate possible mechanistic pathways. CONCLUSIONS This report shows that primary VSV infection can be associated with vasculopathy and CVST. Physicians should recognize this serious complication, which should be diagnosed and treated without delay.
Asunto(s)
Varicela , Trastornos de Cefalalgia , Herpes Zóster , Trombosis de los Senos Intracraneales , Infección por el Virus de la Varicela-Zóster , Adulto , Varicela/complicaciones , Varicela/diagnóstico , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3 , Humanos , Masculino , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de los Senos Intracraneales/tratamiento farmacológico , Trombosis de los Senos Intracraneales/etiología , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Adulto JovenRESUMEN
A novel methodology to access alkynyl nucleoside analogues is elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452-481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, are potential tools for fluorescent tagging, studying nucleoside metabolism, 2'-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds posess antiviral activity (EC50 1.3-13.2 µM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore.
Asunto(s)
Antivirales/química , Antivirales/farmacología , Nucleósidos de Pirimidina/química , Nucleósidos de Pirimidina/farmacología , Antivirales/síntesis química , Línea Celular , Fluorescencia , Halogenación , Herpesvirus Humano 3/efectos de los fármacos , Humanos , Modelos Moleculares , Nucleósidos de Pirimidina/síntesis química , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/virologíaRESUMEN
Primary infection with varicella-zoster virus (VZV) causes chickenpox, a benign and self-limited disease in healthy children. In patients with primary or acquired immunodeficiencies, primary infection can be life-threatening, due to rapid dissemination of the virus to various organs [lung, gastrointestinal tract, liver, eye, central nervous system (CNS)]. We retrospectively described and compared the clinical presentations and outcomes of disseminated varicella infection (DV) in patients with acquired (AID) (n= 7) and primary (PID) (n= 12) immunodeficiencies. Patients with AID were on immunosuppression (mostly steroids) for nephrotic syndrome, solid organ transplantation or the treatment of hemopathies, whereas those with PID had combined immunodeficiency (CID) or severe CID (SCID). The course of the disease was severe and fulminant in patients with AID, with multiple organ failure, no rash or a delayed rash, whereas patients with CID and SICD presented typical signs of chickenpox, including a rash, with dissemination to other organs, including the lungs and CNS. In the PID group, antiviral treatment was prolonged until immune reconstitution after bone marrow transplantation, which was performed in 10/12 patients. Four patients died, and three experienced neurological sequelae. SCID patients had the worst outcome. Our findings highlight substantial differences in the clinical presentation and course of DV between children with AID and PID, suggesting differences in pathophysiology. Prevention, early diagnosis and treatment are required to improve outcome.
Asunto(s)
Síndromes de Inmunodeficiencia , Infección por el Virus de la Varicela-Zóster , Adolescente , Antivirales/uso terapéutico , Niño , Preescolar , Resultado Fatal , Femenino , Humanos , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Lactante , Masculino , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoRESUMEN
PURPOSE: To provide an overview of the current knowledge on the Human Immunodeficiency Virus (HIV)-associated retinopathies. METHODS: A PubMed search was performed, using the key terms "HIV Retinopathy OR Retinitis" and "HIV AND Retinitis" to find manuscripts published within the last ten years. RESULTS: If left untreated, HIV infection causes a progressive immunodeficiency caused by depletion of CD4-positive T lymphocytes. Noninfectious HIV retinopathy, clinically manifested by cotton wool spots. Once the CD4 count drops below 200 c/µl, immunodeficiency creates a vulnerability for systemic opportunistic infections. Within the posterior segment of the eye, cytomegalovirus (CMV) retinitis has to be distinguished from infections with other members of the herpes virus family, as well as from toxoplasmosis, tuberculosis, and syphilis. Upon restoration of the immune system, immune recovery uveitis may manifest in one third of CMV affected eyes. CONCLUSION: Targeted antiviral treatment and secondary recurrence prophylaxis prevent vision loss of the retina prior to immune recovery.
Asunto(s)
Coriorretinitis/virología , Retinitis por Citomegalovirus/virología , Infecciones Virales del Ojo/virología , Infecciones por VIH/complicaciones , Síndrome de Necrosis Retiniana Aguda/virología , Infección por el Virus de la Varicela-Zóster/virología , Antivirales/uso terapéutico , Coriorretinitis/diagnóstico , Coriorretinitis/tratamiento farmacológico , Retinitis por Citomegalovirus/diagnóstico , Retinitis por Citomegalovirus/tratamiento farmacológico , Técnicas de Diagnóstico Oftalmológico , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/tratamiento farmacológico , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Síndrome de Necrosis Retiniana Aguda/diagnóstico , Síndrome de Necrosis Retiniana Aguda/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológicoRESUMEN
BACKGROUND: The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS). CASE PRESENTATION: Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22-52 years). The median symptoms onset to clinic time was 3.5 days (range 3-6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3-7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165-400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147-478 × 10^6/L; median 1.41 g/L, range 0.57-1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10-14 days. All patients recovered completely. CONCLUSIONS: VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.