Update on the diagnosis, management and treatment of fever of unknown origin: review article and case report / Actualización en el diagnóstico, manejo y tratamiento de la fiebre de origen desconocido: artículo de revisión y reporte de caso

INTRODUCTION Actually, there are more than 200 different causes of unknown fever, it is necessary for the doctor to identify the most prevalent causes of unknown fever in our Clinical boar. PRESENTATION A 52-year-old male patient with no history of chronic diseases, which was received in the Emergency Service of the Hospital San Pablo, Coquimbo, on 02/03/20 began a clinical picture characterized by fever up to 39 ºC associated with diaphoresis, evaluated several times in primary health care without response to symptomatic treatment. He denies dyspnea, cough, sputum production, headache, muscle weakness, myalgia, fainting, decreased visual acuity, nausea, vomiting, chest pain, abdominal pain, diarrhea, constipation, altered bowel movements, weight loss, dysuria, bladder tenesmus, pain lumbar, skin lesions. As relevant information, the patient reports having taken amoxicillin/clavulanate for 2 days on his own account. DISCUSSION Physicians should be aware of the rare extent of an unusual presentation of knowledge origin fever, probably associated with Still disease, as well as medical options for treatment. The literature does not conclude on a gold standard for the method of approach. CONCLUSION In our case, the etiological agent that could cause Fever of unknown origin (FUO) was Sars cov-2 given the presence of elevated inflammatory factors and acute phase proteins and the presence of neutrophilic infiltration

Reacciones adversas de los diez fármacos más notificados. Matanzas 2014 al 2017 / Adverse reactions to the ten most reported drugs in Matanzas 2014-2017

RESUMEN Introducción: la toxicidad de los fármacos es compleja y difícilmente valorable, por la cantidad de factores que intervienen en su producción, como modo de aparición, duración y gravedad de las reacciones adversas. La importancia de estas reacciones está dada por la frecuencia y gravedad con que un fármaco o familia de fármacos las producen. Objetivo: caracterizar las principales reacciones adversas que provocan los medicamentos, los grupos de edades con más riesgos, los sistemas de órganos que se afectan, la frecuencia, imputabilidad y la intensidad de las mismas. Materiales y métodos: estudio observacional, descriptivo, de serie de casos en farmacovigilancia. El universo fue las reacciones adversas de los 10 fármacos más notificados por la Unidad Coordinadora Provincial de Farmacovigilancia en Matanzas, en el periodo 2014-2017. Se estudiaron las variables: medicamentos, grupo farmacológico, datos demográficos, nivel de atención, tipo de efecto adverso, intensidad, imputabilidad y frecuencia. Resultados: se notificaron 10 fármacos con 2 216 reacciones. La vacuna pentavalente fue la más notificada, con un 17,6 %, seguido por la amoxicilina y las penicilinas. Predominó el sexo femenino con 1 279 reportes, (59,1 %) y los adultos, con 1 010 notificaciones, (46,6 %). La atención primaria de salud fue la de mayor número de notificaciones, 2 082 reportes, (96,1 %). Las principales reacciones fueron: la erupción cutánea, la fiebre y la urticaria. Predominaron reacciones moderadas; 1 972 reportes, (91,1 %), aquellas clasificadas como probables, 1 887 reportes, (87,1 %) y las frecuentes con 1 284 reportes, (59,2 %). Conclusiones: el sistema de farmacovigilancia en la provincia proporcionó sistemáticamente información sobre la seguridad de los medicamentos, lo que permitió el conocimiento de la relación beneficio-riesgo de los medicamentos presentes en el mercado, así como los más usados.

ABSTRACT Introduction: drugs toxicity is complex and of difficult assessment, due to the quantity of factors intervening in its production, like emergency way, duration, and seriousness of the adverse reactions. The importance of these reactions is given by the frequency and seriousness a drug or a drug family produces them. Objective: to characterize the main adverse reactions caused by medicines, the age groups having higher risk, the most affec6ted systems of organs, frequency, imputability and intensity. Material and methods: descriptive, observational study of a series of cases in pharmacovigilance. The universe was the adverse reactions of the ten drugs most reported by the Provincial Coordinating Unit of Pharmacovigilance in the period 2014-2017. The studied variables were: drugs, pharmacological group, demographic data, health care level, kind of adverse effect, intensity, imputability and frequency. Results: ten drugs were reported with 2 216 reactions. The pentavalent vaccine was the most reported one, with 17.6 %, followed by amoxicillin and penicillin. There was a predominance of the female sex with 1 279 reports (59.1 %), and adult people with 1 010 reports (46.6 %). The highest number of reports was made by the primary health care, 2 082 (96.1 %). The main reactions were skin rash, fever and urticaria. There was a predominance of mild reactions: 1 972 reports (91.1 %); reactions classified as probable: 1 887 reports (87.1 %): ands frequent ones: 1 284 reports (59.2 %). Conclusions: the pharmacovigilance system in the province systematically provided information on drugs´ safeness that allowed knowing the benefit-risk relation of the medicines that are in the market, and also which are the most used ones.

Encefalopatía por virus herpes 6 como complicación de exantema súbito / Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

Predicting Factors of Roseola Infantum Infected with Human Herpesvirus 6 from Urinary Tract Infection

PURPOSE: The aim of this study was to compare the clinical and laboratory features of infants with roseola infantum due to human herpesvirus 6 (HHV6) infection and those with urinary tract infection (UTI). METHODS: We retrospectively reviewed the medical records of children who were hospitalized at Cheil General Hospital and Women's Health Care Center, College of Medicine, Dankook University, and diagnosed as having HHV6 infection or UTI. RESULTS: Among the infants admitted between September 2014 and May 2016, 92 (male, 45 and female, 47) were included in the study and divided into a HHV6 infection group (n=50) and a UTI group (n=42). The relative risk of UTI compared with that of HHV6 infection increased with pyuria (P<0.001), increased with leukocytosis (mean white blood cell [WBC] count, 15,048±5,756/mm³ vs 87,916±54,056/mm³; P<0.001), increased with C-reactive protein (CRP) level (4.89±4.85 mg/dL vs 1.04±1.76 mg/dL; P<0.001), and younger age (6.3±3.2 months vs 18.3±12.6 months; P<0.001). The relative risk of HHV6 infection compared with that of UTI increased with fever duration (4.3±1.7 days vs 2.8±1.7 days; P<0.001) and decreased with platelet (PLT) count (373±94×10³/mm³ vs 229±90×10³/mm³; P<0.001). No significant differences were found between the HHV6 groups according to the presence or absence of pyuria. CONCLUSION: Pyuria, age, fever duration, WBC count, CRP level, and PLT count were the differentiating factors of HHV6 infection from UTI. However, sterile pyuria can occur in children with HHV6 infection. In the presence of pyuria, CRP level and PLT count were the strong predictors of UTI compared with HHV6.

Diagnosis of human herpesvirus 6B primary infection by polymerase chain reaction in young children with exanthematic disease / Diagnóstico de infecção primária pelo herpesvírus humano tipo 6B através da técnica de reação em cadeia da polimerase em crianças com doença exantemática

INTRODUCTION: Exanthem subitum is a classical rash disease of early childhood caused by human herpesvirus 6B (HHV-6B). However, the rash is frequently misdiagnosed as that of either measles or rubella. METHODS: In this study, a nested multiplex polymerase chain reaction (PCR) was used to diagnose HHV-6B primary infection, differentiate it from infections caused by HHV-6A and compare it to antibody avidity tests. The samples were separated into case group and control group according to the results of the indirect immunofluorescence assay (IFA) technique. RESULTS: From the saliva samples analyzed, HHV-6A DNA was detected in 3.2 percent of the case group and in 2.6 percent of the control group. Regarding HHV-6B, PCR detected viral DNA in 4.8 percent of the case group and in 1.3 percent of the control group. Among the serum samples studied, a frequency of 1.7 percent was determined for HHV-6A in the case group and 1.2 percent in the control group. PCR did not detect HHV-6B DNA in serum samples. The sensitivity and specificity of the PCR technique ranged from 0 percent to 4.8 percent and 97.5 percent to 100 percent, respectively, compared to IFA. CONCLUSIONS: The PCR technique was not suitable for diagnosing primary infection by HHV-6B in children with exanthematic disease and should not substitute the IFA.

INTRODUÇÃO: O exantema súbito é uma doença comum durante a infância e pode ser causada pela infecção por herpesvirus humano tipo 6B (HHV-6B). No entanto, a erupção cutânea característica dessa doença, é frequentemente confundida com outras viroses como sarampo ou rubéola. MÉTODOS: Foi utilizada a técnica de reação em cadeia da polimerase (PCR) no formato nested multiplex para o diagnóstico de infecção primária por HHV-6B, diferenciação entre as infecções causadas pelo HHV-6A e comparação com testes de avidez de anticorpos. As amostras foram separadas em grupo caso e grupo controle, de acordo com os resultados do teste de imunofluorescência indireta (IFA). RESULTADOS: Nas amostras de saliva analisadas, o DNA do HHV-6A foi detectado em 3,2 por cento no grupo caso e em 2,6 por cento das amostras do grupo controle. Em relação ao HHV-6B, o DNA viral foi observado em 4,8 por cento no grupo caso e em 1,3 por cento no grupo controle. Após a realização da PCR nas amostras de soro, o DNA do HHV-6A foi detectado em 1,7 por cento no grupo caso e em 1,2 por cento no grupo controle, enquanto o DNA do HHV-6B não foi detectado. A sensibilidade e a especificidade da técnica de PCR variaram de 0 por cento a 4,8 por cento e de 97,5 por cento a 100 por cento, respectivamente, quando comparado com a IFA. CONCLUSÕES: A técnica de PCR não se mostrou adequada para o diagnóstico de infecção primária pelo HHV-6B em crianças com doença exantemática e não deve substituir a IFA.

Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum

In this study, we assessed the prevalence of human herpesvirus-7 (HHV-7) in 141 serum samples from children less than four years of age with exanthematic disease. All samples were negative for measles, rubella, dengue fever and parvovirus B19 infection. Testing for the presence of human herpesvirus-6 (HHV-6)-specific high avidity IgG antibodies by indirect immunofluorescence assay (IFA) revealed two main groups: one composed of 57 patients with recent primary HHV-6 infection and another group of 68 patients showing signs of past HHV-6 infection. Another 16 samples had indeterminate primary HHV-6 infection, by both IgG IFA and IgM IFA. Serum samples were subjected to a nested polymerase chain reaction to detect the presence of HHV-7 DNA. Among patients with a recent primary HHV-6 infection, HHV-7 DNA was present in 1.7 percent of individuals; however, 5.8 percent of individuals tested positive for HHV-7 DNA in the group with past primary HHV-6 infection. Among the 16 samples with indeterminate diagnosis, 25 percent (4/16) had HHV-7 DNA (p < 0.002). We hypothesise that HHV-7 might be the agent that causes exanthema. However, a relationship between clinical manifestations and the detection of virus DNA does not always exist. Therefore, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease. In conclusion, we detected HHV-7 DNA in young children from the state of Rio de Janeiro, Brazil.

Optimization of the Sybr Green real time PCR for the detection of Human Herpes Virus type 6 (HHV-6) / Otimização da PCR em tempo real - Sybr Green para detecção do Herpes Vírus Humano tipo 6 (HHV-6)

HHV-6 is the etiological agent of Exanthem subitum which is considered the sixth most frequent disease in infancy. In immuno-compromised hosts, reactivation of latent HHV-6 infection may cause severe acute disease. We developed a Sybr Green Real Time PCR for HHV-6 and compared the results with nested conventional PCR. A 214 pb PCR derived fragment was cloned using pGEM-T easy from Promega system. Subsequently, serial dilutions were made in a pool of negative leucocytes from 10-6 ng/µL (equivalent to 2465.8 molecules/µL) to 10-9 (equivalent to 2.46 molecules/µL). Dilutions of the plasmid were amplified by Sybr Green Real Time PCR, using primers HHV3 (5' TTG TGC GGG TCC GTT CCC ATC ATA 3)'and HHV4 (5' TCG GGA TAG AAA AAC CTA ATC CCT 3') and by conventional nested PCR using primers HHV1 (outer): 5'CAA TGC TTT TCT AGC CGC CTC TTC 3'; HHV2 (outer): 5' ACA TCT ATA ATT TTA GAC GAT CCC 3'; HHV3 (inner) and HHV4 (inner) 3'. The detection threshold was determined by plasmid serial dilutions. Threshold for Sybr Green real time PCR was 24.6 molecules/µL and for the nested PCR was 2.46 molecules/µL. We chose the Real Time PCR for diagnosing and quantifying HHV-6 DNA from samples using the new Sybr Green chemistry due to its sensitivity and lower risk of contamination.

HHV-6 é o agente etiológico do Exantema Súbito e considerado a sexta doença mais comum na infância. Em indivíduos imunocomprometidos, a reativação da infecção latente pode causar doença aguda ou morte. Padronizamos PCR em Tempo Real utilizando a química Sybr Green na detecção do HHV-6 e comparamos os resultados com a PCR convencional. Um fragmento de 214 pb foi clonado através do kit pGEM-T do sistema Promega. Com este clone, foram feitas diluições seriadas em um pool de leucócitos negativos a partir de 10-6 ng/µL (equivalente a 2465,8 moleculas/µL) até 10-9 (equivalente a 2,46 moleculas/µL). As diluições foram amplificadas por PCR em Tempo Real utilizando Sybr Green, com primers HHV3 5' TTG TGC GGG TCC GTT CCC ATC ATA 3' e HHV4 5' TCG GGA TAG AAA AAC CTA ATC CCT 3' e pelo método convencional, PCR nested usando primers HHV1 (externo): 5' CAA TGC TTT TCT AGC CGC CTC TTC 3'; HHV2 (externo): 5' ACA TCT ATA ATT TTA GAC GAT CCC 3', HHV3 (interno) e HHV4 (interno): 5' TCG GGA TAG AAA AAC CTA ATC CCT 3'. O limite de detecção foi determinado pelas diluições seriadas do plasmídio contendo um fragmento de HHV6: para o ensaio com Sybr Green, foi de 24,6 moleculas/µL e para a PCR nested, 2,46 moleculas/µL. Elegemos o PCR em Tempo Real - Sybr Green como método diagnóstico e quantitativo do HHV-6 devido a sua boa sensibilidade e menor risco de contaminação.

Implantación anómala de la arteria coronaria izquierda en un lactante / Anomalous establishment of the left coronary artery in a nursing one

Las anomalías de las arterias coronarias constituyen el 2.2 por ciento de las cardiopatías congénitas1. La implantación de la arteria coronaria izquierda (ACI) desde el tronco de la arteria pulmonar (AP) también conocida como síndrome de Bland y White y Garland o ALCAPA (anomalous left coronary artery from the pulmonary artery) es la anormalidad coronaria más frecuente. Las manifestaciones clínicas son derivadas de la isquemia miocárdica, consecuencia del cortocircuito arteriovenoso. La presencia de cardiomegalia asociada a falla cardiaca es un hallazgo común en neonatos y lactantes mientras que en niños mayores y adultos son más frecuentes el infarto agudo de miocardio, arritmias, signos de falla cardiaca o muerte súbita2...

Detecção molecular da reativação simultânea de VZV e HSV em paciente com história clínica de roseola infantum / Molecular detection of simultaneous reactivation of VZV and HSV in a patient with a clinical history of roseola infantum

Paciente masculino de 29 anos, portador de um quadro febril acompanhado de exantema generalizado, com suspeita de roseola infantum, apresentou desconforto e hiperemia do olho direito, além de lesöes labiais vesiculares. Através da técnica da PCR diagnosticou-se que a lesäo labial fora provocada pelo vírus do herpes simples e a lesäo ocular produzida pelo vírus da varicela-zoster

Outbreaks of human-herpes virus 6 (HHV-6) infection in day-care centers in Belém, Pará, Brazil

A total of 730 children aged less than 7 years, attending 8 day-care centers (DCCs) in Belém, Brazil were followed-up from January to December 1997 to investigate the occurrence of human-herpes virus 6 (HHV-6) infection in these institutional settings. Between October and December 1997 there have been outbreaks of a febrile- and -exanthematous disease, affecting at least 15-20 percent of children in each of the DCCs. Both serum- and- plasma samples were obtained from 401 (55 percent) of the 730 participating children for the detection of HHV-6 antibodies by enzyme-linked immunosorbent assay (ELISA), and viral DNA amplification through the nested-PCR. Recent HHV-6 infection was diagnosed in 63.8 percent (256/401) of them, as defined by the presence of both IgM and IgG-specific antibodies (IgM+/IgG+); of these, 114 (44.5 percent) were symptomatic and 142 (55.5 percent) had no symptoms (p = 0.03). A subgroup of 123 (30.7 percent) children were found to be IgM-/IgG+, whereas the remaining 22 (5.5 percent) children had neither IgM nor IgG HHV-6- antibodies (IgM-/IgG-). Of the 118 children reacting strongly IgM-positive ( > or = 30 PANBIO units), 26 (22.0 percent) were found to harbour the HHV-6 DNA, as demonstrated by nested-PCR. Taken the ELISA-IgM- and- nested PCR-positive results together, HHV-6 infection was shown to have occurred in 5 of the 8 DCCs under follow-up. Serological evidence of recent infections by Epstein-Barr virus (EBV) and parvovirus B19 were identified in 2.0 percent (8/401) and 1.5 percent (6/401) of the children, respectively. Our data provide strong evidence that HHV-6 is a common cause of outbreaks of febrile/exanthematous diseases among children attending DCCs in the Belém area

Enfermedades infecciosas / Infectious diseases

Esta parte contiene los siguientes temas: sarampión, rubeóla, parotiditis, citomegalovirus, mononucleosis infecciosa, eritema infeccioso, exantema súbito, toxoplasmosis, infecciones por enterovirus, varicela-zoster, infecciones por salmonella, shigelosis, paludismo, chagas agudo, dengue, inmunizaciones, uso racional de agentes antinfecciosos

Apresentacao clinica de 52 criancas com exantema causado pelo Herpesvirus Humano tipo 6 / Clinical profile of 52 children with exhantem caused by human herpvirus type 6

Os autores descrevem e analisam manifestacoes clinicas observadas em criancas com exantema causado pelo Herpesvirus tipo 6. Foi realizado estudo prospectivo no Servico de Pronto-Atendimento Pediatrico do Hospital Universitario da USP, durante 15 meses, com as criancas que apresentavam exantema generalizado nao-bolhoso. Os pacientes deste grupo inicial foram examinados e receberam um diagnostico clinico previo. Destas criancas, foram incluidas na casuistica do presente estudo apenas as criancas menores de tres anos, que tivessem comprovacao laboratorial da presenca do Herpesvirus tipo 6 no sangue. O estudo laboratorial foi realizado atraves da reacao de polimerizacao em cadeia do acido nucleico do Herpesvirus humano tipo 6, em linfocitos de sangue periferico...

Seroepidemiology of human herpesvirus 6 in a population seen in the University Hospital, Kuala Lumpur, Malaysia.

Sera from healthy donors and patients stored over a period of 2 years, aged 1 to 83 years, were examined for reactivity to human herpes virus 6 (HHV-6) by the standard indirect immunofluorescence assay (IFA). Of the 600 serum specimens screened, 502 showed positive reactivity to HHV-6. This gives an overall seropositive rate of 83.7%. There is no significant difference in the overall positive rate between the ethnic groups (Chinese, Malays, Indians) (chi 2 = 0.35 df = 2 p > 0.05). However, there is significant difference in the positive rates at the extreme age groups of 1 year as well as 61 years and above. From birth up to below 1 year of age, the seroprevalence rate was 82%. At one year of age the positive rate decreased to 66% before gradually rising so that the percentage seropositivity of 6 to 10 years old becomes similar to that in older children and adults (11 to 40 years). The positive rate then starts to decline after 40 years of age. Using a standardized scoring system, the corresponding antibody titer was found to be high in the very young population and starts to decline after the age of 15 years. This suggests that in our population group, primary infection occurs mainly in the pediatric age group. It also accounts for the low positive rate in the age group of 61 years and above, as by then the titer had fallen to the level below the detection limits of the assay system.