Mononeuritis multiplex: an uncommon neurological manifestation of cytomegalovirus reactivation in an HIV-infected patient.

BACKGROUND: Cytomegalovirus (CMV) reactivation with neurological involvement in patients with acquired immunodeficiency syndrome (AIDS) is increasingly rare since the introduction of antiretroviral therapy (ART). Manifestations include encephalitis, myelitis, polyradiculopathy and, less commonly, mononeuritis multiplex (MNM). We report a case of disseminated CMV disease with gastrointestinal and peripheral and central nervous system involvement in a patient with AIDS, manifesting primarily as MNM. CASE PRESENTATION: A 31-year old woman with AIDS presented with a clinical picture of MNM. Electromyography confirmed the clinical findings. CMV DNA was detected in cerebrospinal fluid (CSF) and blood. Gastrointestinal involvement was histologically documented. HIV RNA was also detected in CSF and brain MRI was consistent with HIV encephalopathy. A diagnosis of disseminated CMV disease (with esophagitis, colitis, encephalitis and MNM) and HIV encephalopathy was made. Treatment consisted of ganciclovir and foscarnet, followed by maintenance therapy with valganciclovir. Evolution was favorable and valganciclovir was stopped after sustained immune recovery following ART initiation. CONCLUSION: We discuss the diagnostic approach to CMV neurological disease, with a focus on MNM and CMV encephalitis. Combination therapy with ganciclovir and foscarnet should be considered for all forms of neurological involvement, although available data are scarce. Since there is significant overlap between CMV encephalitis and HIV encephalopathy, ART drugs with higher CSF penetration may have to be considered. ART and immune recovery are essential to improve outcomes.

Non-falciparum malaria imported mainly from Africa: a review from a Portuguese hospital.

BACKGROUND: Non-falciparum malaria (NFM) has been reported to be responsible for around 25% of imported malaria cases in Europe but is often neglected due to its less severe clinical course when compared to Plasmodium falciparum. Differentiation between species is however crucial for a correct approach. The objective of this study is to report the cases of this often missed aetiology of malaria in a tertiary hospital in Portugal. METHODS: Data were retrospectively analysed from patients admitted from January 2006 to August 2016 with a NFM diagnosis based on microscopy, rapid diagnostic tests (RDT) (BinaxNow®) and/or PCR. Epidemiologic and clinical aspects were reviewed. RESULTS: A total of 19 NFM cases were diagnosed, corresponding to 8.4% of the total 225 cases of malaria. Seventeen (89%) were male with a median age of 41 years. All but one case were imported from sub-Saharan Africa, with 12 (63%) of the cases returned from Angola. Microscopy was positive for all patients and correctly identified the species in 12 (63%) patients. BinaxNOW® was performed in all patients and it was positive in 11 cases, showing a sensitivity of 58%. PCR was performed in nine patients and was positive in eight of them, being responsible for the identification of the species in four cases. Plasmodium malariae accounted for 37% (n = 7) of the cases, Plasmodium ovale for 32% (n = 6) and Plasmodium vivax for 17% (n = 3). In three (16%) patients, morphology was suggestive of P. vivax or P. ovale, but precise species identification was not possible. Regarding presentation, fever was the most reported symptom, and the most frequent laboratory finding was thrombocytopaenia. Quinine-doxycycline was prescribed in eleven patients (58%), chloroquine in six cases (32%) and artemether-lumefantrine in two (11%). All of the patients showed clinical improvement. CONCLUSIONS: NFM remains an important cause of imported malaria in patients from sub-Saharan Africa, alone or as mixed infection with P. falciparum. Access to PCR techniques facilitates diagnosis, as low sensitivity from RDTs and microscopy are to be expected.

Artemether-lumefantrine and liver enzyme abnormalities in non-severe Plasmodium falciparum malaria in returned travellers: a retrospective comparative study with quinine-doxycycline in a Portuguese centre.

BACKGROUND: Artemisinin-based therapy is the current standard treatment for non-severe malaria due to Plasmodium falciparum. The potential for asymptomatic liver toxicity of this therapy and its implication in clinical practice is currently unknown. The aim of this study is to assess the hepatic function in patients treated with a standard three-day artemisinin-based regimen and to compare it with the quinine-doxycycline regimen. METHODS: Retrospective and comparative study of returned adult travellers admitted with non-severe P. falciparum malaria. Fifty-seven patients were included: 19 treated with artemisinin-based therapy and 38 with quinine-doxycycline therapy. RESULTS: During treatment, when compared with quinine-doxycycline group, the artemisinin-lumefantrine group presented a higher proportion of significant liver enzyme abnormalities (42 vs. 5%, p < 0.01) and a higher peak value of aspartate aminotransferase (131 vs. 64 U/L, p < 0.01) and alanine aminotransferase (99 vs. 75 U/L, p = 0.05). None of the patients was symptomatic, there were no treatment interruptions and all patients achieved clinical cure. CONCLUSIONS: Treatment of uncomplicated falciparum malaria with artemisinin-based therapy might cause asymptomatic liver enzyme abnormalities in the first days of treatment. Nevertheless, these liver enzyme abnormalities seem to be harmless, asymptomatic and self-limited.

Acute HIV infection presenting as hemophagocytic syndrome with an unusual serological and virological response to ART.

BACKGROUND: HIV clinical presentation in the acute stage is variable and some of its virological and immunological aspects are not completely understood. Most cases of HIV- associated reactive hemophagocytic syndrome have been reported in patients with advanced stages of HIV and to our knowledge, there are only 8 cases in the English literature presenting during acute HIV infection, most in East Asia, being this the first case in a European patient. CASE PRESENTATION: We report a case of a European Caucasian 27- year old woman with a primary HIV- infection presenting with extremely low CD4+ T cell count who developed a haemophagocytic syndrome after starting ART and in whom we documented a very unusual serological and virological response, characterized by an impaired HIV- antibody production and a 12 month time frame to reach an undetectable viral load, despite no evidence of resistance. CONCLUSIONS: This case report apart from describing an unusual clinical presentation of an acute HIV infection as hemophagocytic syndrome provides useful information that might contribute for understanding some subtle issues in acute HIV infection, namely the dynamics of virological and immunological aspects after antiretroviral therapy initiation.

Increased viability but decreased culturability of Mycobacterium avium subsp. paratuberculosis in macrophages from inflammatory bowel disease patients under Infliximab treatment.

Mycobacterium avium subsp. paratuberculosis (MAP) has long been implicated as a triggering agent in Crohn's disease (CD). In this study, we investigated the growth/persistence of both M. avium subsp. hominissuis (MAH) and MAP, in macrophages from healthy controls (HC), CD and ulcerative colitis patients. For viability assessment, both CFU counts and a pre16SrRNA RNA/DNA ratio assay (for MAP) were used. Phagolysosome fusion was evaluated by immunofluorescence, through analysis of LAMP-1 colocalization with MAP. IBD macrophages were more permissive to MAP survival than HC macrophages (a finding not evident with MAH), but did not support MAP active growth. The lower MAP CFU counts in macrophage cultures associated with Infliximab treatment were not due to increased killing, but possibly to elevation in the proportion of intracellular dormant non-culturable MAP forms, as MAP showed higher viability in those macrophages. Increased MAP viability was not related to lack of phagolysosome maturation. The predominant induction of MAP dormant forms by Infliximab treatment may explain the lack of MAP reactivation during anti-TNF therapy of CD but does not exclude the possibility of MAP recrudescence after termination of therapy.

Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease.

Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.

The workup process of vaccination in IBD patients needs a change-Insights from a multinational survey.

BACKGROUND: Immunosuppressive medications play a crucial role in inflammatory bowel disease (IBD) but increase susceptibility to infections, underlining the importance of vaccination. Nevertheless, vaccination rates are often low. AIMS: This study assessed the perspective of gastroenterologists (GEs) on vaccination of IBD patients. METHODS: An online survey was applied to GEs worldwide, from 10/2022 to 06/2023. RESULTS: The 271 respondents considered vaccination important, however, 26 % never/rarely prescribed vaccines and 60 % admitted having limited or no confidence on managing their side effects - GEs practicing in Europe, male and older more often felt capable of this. Female and younger participants were more aware of the need to alter the current workflow in vaccination. Some respondents proposed to delegate the responsibility of vaccination to general practitioners, nurses in gastroenterology units, or infectious diseases specialists, but 19 % considered that no change was needed. CONCLUSION: Overall, the importance of addressing vaccine hesitancy, providing flyers to patients, and implementing vaccine guidelines were consensually recognized. The data indicated that the vaccination process needs reformulation and that different opinions/attitudes toward vaccines are influenced by demographic factors, workplace characteristics, affiliation, and teaching activities. Delegating the responsibility of vaccination and adopting a multidisciplinary approach seem like effective strategies to increase vaccination coverage among IBD patients.

Vaccines - beliefs and concerns: the voice of patients with inflammatory immunomediated diseases.

BACKGROUND: Vaccination is a key issue in patients with immunomodulated inflammatory diseases on immune-mediated therapy. Still, vaccination rates in these patients are low. This study aimed to assess the knowledge and fears of patients with immune-mediated inflammatory diseases (IMIDs) regarding vaccines, with the ultimate goal of increasing vaccination rates through the definition and implementation of more effective communication strategies with the patient. METHODS: This study was conducted in a Portuguese hospital, between January 2019-December 2020, and included adult patients with an IMID. A questionnaire was developed and applied to evaluate knowledge and fears regarding vaccines. RESULTS: From the 275 included patients, more than 90% answered correctly to all questions on general knowledge, with an exception for the question related to protection from severe disease, without differences between age groups or education levels, except for the question about vaccine contraindications (P = 0.017). Regarding vaccines in immunocompromised hosts, the proportion of correct answers was lower and significantly different between education levels (P = 0.00-0.042),. More than 50% of the participants showed moderate to very high concern about several aspects of vaccines, with differences between age groups (P = 0.018). CONCLUSION: Our patients have general knowledge of vaccines but regarding vaccines in immunocompromised patients knowledge is lower and dependent on the education level. In addition, age influences the pattern of concerns related to vaccines. The information gathered in this study shall be considered to identify potential local interventions targeted to improve vaccination.

Adherence to Vaccines in Adult Patients with Immune-Mediated Inflammatory Diseases: A Two-Year Prospective Portuguese Cohort Study.

BACKGROUND: Patients with immune-mediated inflammatory diseases (IMIDs) treated with immunomodulatory therapy present an increased susceptibility to infections. Vaccination is a crucial element in the management of IMID patients; however, rates remain suboptimal. This study intended to clarify the adherence to prescribed vaccines. MATERIALS AND METHODS: This prospective cohort study included 262 consecutive adults with inflammatory bowel disease and rheumatological diseases who underwent an infectious diseases evaluation before initiating or switching immunosuppressive/biological therapy. Vaccine prescription and adherence were assessed during an infectious diseases (ID) consultation using a real-world multidisciplinary clinical project. RESULTS: At baseline, less than 5% had all their vaccines up-to-date. More than 650 vaccines were prescribed to 250 (95.4%) patients. The most prescribed were pneumococcal and influenza vaccines, followed by hepatitis A and B vaccines. Adherence to each of the vaccines ranged from 69.1-87.3%. Complete adherence to vaccines occurred in 151 (60.4%) patients, while 190 (76%) got at least two-thirds of them. Twenty patients (8%) did not adhere to any of the vaccines. No significant differences were found in the adherence rates of patients with different sociodemographic and health-related determinants. CONCLUSIONS: ID physicians can play a role in the process of increasing vaccine prescription and adherence. However, more data on patients' beliefs and vaccine hesitancy, along with mobilization of all health care professionals and adequate local interventions, shall be considered to improve vaccine adherence.

Severe imported malaria in an intensive care unit: a review of 59 cases.

BACKGROUND: In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU). METHODS: Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011) and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS), malaria score for adults (MSA), simplified acute physiology score (SAPSII) and a score based on WHO's malaria severe criteria were applied. Statistical analysis was performed using StataV12. RESULTS: Fifty nine patients were included in the study, all but three were adults; 47 (79,6%) were male; parasitaemia on admission, quantified in 48/59 (81.3%) patients, was equal or greater than 2% in 47 of them (97.9%); the most common complications were thrombocytopaenia in 54 (91.5%) patients, associated with disseminated intravascular coagulation (DIC) in seven (11.8%), renal failure in 31 (52.5%) patients, 18 of which (30.5%) oliguric, shock in 29 (49.1%) patients, liver dysfunction in 27 (45.7%) patients, acidaemia in 23 (38.9%) patients, cerebral dysfunction in 22 (37.2%) patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2%) patients, hypoglycaemia in 18 (30.5%) patients; 29 (49.1%) patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were not associated with death in this cohort. CONCLUSION: Severe malaria cases should be continued monitored in the ICUs. SAPS II and the WHO score are good predictors of mortality in malaria patients, but other specific scores deserve to be studied prospectively.

Travel-Related Diseases and Injuries in Children and Adolescents: A Post-Travel Surveillance Questionnaire Assessment.

INTRODUCTION: Children and adolescents are a relevant and increasing proportion of travelers. Injuries and infectious diseases in children are safety concerns when traveling. However, data on diseases and injuries during international travels in children are not available. The aims of this study were to analyze travel-related diseases and injuries among pediatric travelers during and after international trips, to identify risk factors for travel-associated disease, and to evaluate the compliance and effectiveness of the recommendations provided in pre-travel appointments. MATERIAL AND METHODS: We enrolled travelers aged under 18 years attending a pre-travel clinic, in a tertiary hospital (2017 - 2019); 223 of the 370 pediatric travelers attending the pre-travel clinic were included. The study was based on a questionnaire designed to address health and safety issues - vaccines and chemoprophylaxis, including side effects, the occurrence of disease or injury, diagnosis, treatment, and outcomes. RESULTS: The median age at pre-travel evaluation was eight years; 39.7% of the travelers were adolescents, 52.5% were female. The participants traveled to 40 countries across four continents, with a median travel duration of 14.5 days. Asia was the most visited continent. Traveling was safe for 84.8%. From 34 travelers who had illness/injury, gastrointestinal symptoms were elicited in 41.2%. Sixteen (47.1%) travelers required an urgent medical appointment at the destination, and no one was hospitalized. Destinations in Africa and longer trips were significantly associated with a higher occurrence of disease/injury (p = 0.023 and p < 0.001, respectively). In a multivariable model, traveling to Africa was still significantly associated with travel-related disease/injury [OR = 2.736 (1.037 - 7.234)]. CONCLUSION: Disease/injury occurred in 15.2% of pediatric travelers. Even though 47.1% of the travelers required an urgent medical appointment, the developed conditions were not severe enough to warrant hospitalization. Travels to Africa and longer trips seem to be associated with a higher risk of disease and injury.

Introdução: As crianças e adolescentes representam uma proporção relevante e crescente de viajantes. As doenças infeciosas e as lesões em crianças durante viagens internacionais são motivo de preocupação relacionada com segurança; no entanto, os dados na idade pediátrica são amplamente desconhecidos. Os objetivos deste estudo foram analisar as doenças e lesões relacionadas com as viagens ocorridas em viajantes em idade pediátrica, durante e após viagens internacionais, identificar fatores de risco para a ocorrência de doenças associadas à viagem, e avaliar o cumprimento e a eficácia das recomendações fornecidas na consulta pré-viagem. Material e Métodos: Incluímos viajantes com idade inferior a 18 anos avaliados na consulta do viajante num hospital terciário (2017 - 2019). O estudo baseou-se num questionário, desenhado para abordar questões de saúde e segurança ­ vacinas e quimioprofilaxia, incluindo efeitos colaterais, ocorrência de doença ou lesão, diagnóstico, tratamento e resultado. Resultados: Foram incluídos 223 dos 370 viajantes pediátricos observados na consulta do viajante. A mediana da idade à data da consulta era oito anos, 39,7% eram adolescentes e 52,5% eram do sexo feminino. Os participantes viajaram para 40 países, em quatro continentes, e a mediana da duração da viagem foi 14,5 dias. O continente asiático foi o mais visitado. A viagem foi segura em 84,8% dos casos. Nos 34 viajantes que apresentaram doença/lesão, verificaram-se sintomas gastrointestinais em 41,2%. Dezasseis (47,1%) viajantes necessitaram de consulta médica urgente no destino e nenhum foi hospitalizado. Destinos em África e viagens mais longas foram associados, significativamente, a maior ocorrência de doença/lesão (p = 0,023 e p < 0,001, respetivamente). No modelo multivariável, viajar para África foi associado, significativamente, a doença/lesão [OR = 2,736 (1,037 - 7,234)]. Conclusão: A viagem associou-se a doença/lesão em 15,2% dos viajantes pediátricos. Embora não requerendo hospitalização, 47,1% dos viajantes necessitaram de consulta médica urgente. África e viagens mais longas parecem estar associados a risco maior de doenças/lesões.

[Guidelines for the Treatment and Follow-Up of Patients with Q Fever]. / Recomendações para o Tratamento e Seguimento de Doentes com Febre Q.

Q fever (or query fever) is a zoonotic infectious disease with worldwide distribution transmitted by an intracellular Gram-negative bacterium, Coxiella burnetii. The most common identified sources of human infection are farm animals, such as sheep, goats and cattle. The disease is endemic in mainland Portugal, with most cases notified in the central and southern regions. Q fever is a complex and pleomorphic disease, with those affected presenting with a wide range of manifestations from acute self-limited flu-like symptoms with good prognosis to persistent localized forms that may harbor a poor prognosis. Cases might occur in an isolated fashion or following outbreaks with great public health repercussion, as seen recently in the Netherlands from 2007 to 2010. Given the complexity of this infection, there is no universal consensus to date on the best strategy to manage Q fever patients. These guidelines provide recommendations regarding the treatment and follow-up of these patients, based on studies, on the author's experience and on the opinion of international experts. The aim is to harmonize the management of these patients taking into account not only the clinical manifestations but also the risk factors of the host in order to reduce disease-associated morbidity and mortality.

A febre Q (do inglês query fever) é uma zoonose de distribuição mundial transmitida por uma bactéria intracelular Gram negativo, Coxiella burnetii. Os ruminantes domésticos são os principais reservatórios implicados na transmissão da doença ao ser humano. Em Portugal continental, esta doença é endémica, com o maior número de casos notificados nas regiões Centro e Sul. A doença causada por C. burnetii é complexa e polimórfica, podendo manifestar-se sob uma forma aguda autolimitada do tipo gripal, com um curso ligeiro a moderado e prognóstico benigno, e/ou sob uma forma persistente, geralmente localizada e de evolução grave ou potencialmente fatal. Pode ocorrer em casos isolados ou em contexto de surtos, alguns com importantes implicações em saúde pública, como o verificado na Holanda em 2007 - 2010. Dada a complexidade e espetro clínico da febre Q, não existe um consenso universal sobre a melhor forma de tratamento, gestão e seguimento destes doentes. Este protocolo é uma sugestão de tratamento e seguimento dos doentes com febre Q, compilando a informação de estudos e opiniões de peritos internacionais e a experiência dos autores. Pretende-se assim uniformizar a gestão destes doentes tendo em conta não só o espetro das suas manifestações clínicas, mas também os fatores de risco do hospedeiro, por forma a reduzir morbimortalidade que a doença possa causar.

[Human Rabies: Optimization of Prevention and Paths Towards the Cure]. / Raiva Humana: Optimização da Prevenção e Caminhos Para a Cura.

INTRODUCTION: Rabies is one of the oldest and deadliest infectious diseases known by human beings and is commonly transmitted by animal bites. Dogs have a major role in the transmission of the virus. Rabies has no approved curative therapy, and its prevention, even though it is highly effective, it is complex, expensive and challenging in terms of accessibility, particularly regarding immunoglobulin. This review aims to provide a practical approach to cost-effective prevention as well as the future perspectives regarding the development of an effective and secure cure. MATERIAL AND METHODS: This review article was based on a search in PubMed using the following MeSH terms: rabies, preexposure and postexposure prophylaxis, rabies immune globulin, treatment, Milwaukee Protocol. RESULTS: Concerning rabies infection, it's important to apply the prevention protocols effectively as early as possible due the unpredictable time window between infection and the appearance of symptoms. The literature shows that is possible to reduce the vaccination dosage and maintain the efficiency of the immunization, and booster vaccination is only required in specific risk groups/populations. DISCUSSION: The current philosophy of cost-effective prevention which consists of canine vaccination, restriction of vaccine overdosage used in humans and the appropriate use of rabies immunoglobulin - could make the prevention of the disease accessible for those countries that need it the most. There are several therapies in development but they're all in early stages of development. CONCLUSION: The development of new and more effective therapeutic and prophylactic approaches is a goal not yet achieved and relies on a better understanding of the disease pathophysiology.

Introdução: A raiva é uma das doenças infecciosas mais antigas e fatais conhecidas pelo ser humano e é maioritariamente transmitida por mordeduras de animais. O cão é o principal vector. A raiva não possui uma terapia curativa aprovada e a sua prevenção ainda que possua altas taxas de eficácia, é complexa, dispendiosa e nem sempre conseguida, muito devido às dificuldades de acesso da imunoglobulina. Esta revisão pretende analisar uma abordagem prática de uma prevenção custo-efectiva e as perspectivas futuras em desenvolvimento de uma cura eficaz e segura.Material e Métodos: Foi utilizada a base de dados da PubMed para pesquisa bibliográfica. Usaram-se os termos MeSH: 'rabies', 'preexposure prophylaxis', 'postexposure prophylaxis', 'rabies immune globulin', 'treatment' e 'Milwaukee Protocol'.Resultados: Relativamente à raiva, é importante executar os protocolos de prevenção atempadamente, devido à imprevisível janela de tempo entre a infecção e a sintomatologia. A literatura mostra que é possível reduzir a dose de vacina mantendo uma eficiente imunização, e que doses de reforço só são necessárias em grupos/populações de risco.Discussão: A actual filosofia de uma prevenção custo-efectiva, que assenta na vacinação canina, restrição de sobredose das vacinas usadas em seres humanos e o uso inteligente da imunoglobulina rábica ­ irá permitir maior acessibilidade da prevenção da doença aos países que mais carecem dela. Encontram-se em progresso terapias promissoras, ainda em estadios precoces de estudo.Conclusão: O desenvolvimento de novas abordagens terapêuticas e profilácticas mais eficazes é um objectivo ainda não alcançado e depende de uma melhor compreensão da patogénese subjacente à doença.

Infectious Risk Mitigation in Patients with Multiple Sclerosis under Disease-Modifying Therapies - the Experience of a Collaborative Neurology-Infectious Diseases Approach.

BACKGROUND: Multiple sclerosis treatment has changed in the last years with the emergence of new disease-modifying therapies (DMTs). Despite a better efficacy profile, these drugs raise concerns about infectious risk, which needs to be mitigated. OBJECTIVE: To analyze the results of a systematic collaborative approach between Neurology and Infectious Diseases (ID) Departments in the management of infectious risk and complications in MS patients treated with DMT. METHODS: Retrospective collection of MS patients' demographic and clinical data from clinical records of MS and ID outpatient clinics (2011-2017). RESULTS: We included 149 patients: most had evidence of previous contact with Herpesviridae, and half of them were not immune to hepatitis A and B viruses (HAV and HBV). Vaccines for HAV, HBV, and Streptococcus pneumoniae were administered in 91%, 78%, and 88% of non-immune patients, respectively. JC virus serology monitoring prevented natalizumab (NTZ) initiation or prompted its switch in 34/122 patients. Forty patients had latent tuberculosis, in which 88% were treated. Infectious events occurred in 33 patients, mostly mild urinary, respiratory, and herpes virus group infections. Only three patients required inpatient care. CONCLUSION: Facing the expansion of the new DMT, we highlight the benefits of an interdisciplinary approach for safer use of the chosen treatment.

COVID-19 in gastroenterology: Where are we now? Current evidence on the impact of COVID-19 in gastroenterology.

BACKGROUND: The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. OBJECTIVE: At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. METHODS/RESULTS/CONCLUSION: We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

The daily impact of COVID-19 in gastroenterology.

A new strain of coronavirus, called SARS-CoV-2, emerged in Wuhan, China, in December 2019, probably originating from a wild-animal contamination. Since then, the situation rapidly evolved from a cluster of patients with pneumonia, to a regional epidemic and now to a pandemic called COrona VIrus Disease 2019 (COVID-19). This evolution is related to the peculiar modes of transmission of the disease and to the globalization and lifestyle of the 21st century that created the perfect scenario for virus spread. Even though research has not evidenced particular susceptibility of inflammatory bowel disease (IBD) patients to SARS-CoV-2 infection, immunosuppressive and immunomodulatory treatments were considered potential risk factors. In this context, initiating treatments with these agents should be cautiously weighted and regular ongoing treatments shall be continued, while the dose of corticosteroids should be reduced whenever possible. Due to the increased risk of contamination, elective endoscopic procedures and surgeries should be postponed and IBD online appointments shall be considered. IBD patients shall also follow the recommendations provided to the general population, such as minimization of contact with infected or suspected patients and to wash hands frequently. In the absence of effective treatments and vaccines, this pandemic can only be controlled through prevention of SARS-CoV-2 transmission with the main objectives of providing patients the best healthcare possible and reduce mortality.

Prospective study of blood viral load of Epstein-Barr virus, herpes virus type 6 and human parvovirus B19 in Crohn's disease: Does therapy matter?

BACKGROUND: The interplay between inflammatory bowel disease (IBD) and DNA viruses, such as Epstein-Barr (EBV), human parvovirus B19 (HPVB19) and human herpes type 6 (HHV6) is scarcely studied. The main aim of this prospective study is to screen for EBV, HSV6, and HPVB19 DNA viremia in adult patients with stable Crohn's disease (CD), correlating the results with IBD treatment. METHODS: From July 2015 - March 2017, 100 patients were enrolled and divided in four groups of 25 participants each, according to in course treatment. Blood collections were performed every 5 months in all patients. Antibodies for EBV and HPVB19 were screened and repeated if negative. Blood EBV DNA, HPVB19 DNA, and HHV6 DNA were quantified by quantitative real-time Polymerase Chain Reaction. RESULTS: Patients had evidence of EBV (100 %) and HPVB19 (70 %) past infection. Across the study timeline, EBV-DNA, HPVB19-DNA, and HHV6-DNA were detected in the blood of 25, 11, and 7 patients, respectively. Viremia was detected only once in 72 %, 73 %, and 86 % of the patients in the studied period, for EBV, HPVB19, and HHV6, respectively. We did not find significant differences between treatment groups, independently of the viral cut-off for the three viruses. CONCLUSIONS: The detection of EBV, HPVB19, and HHV6 viremia, in stable CD patients, was not impacted by biological/immunosuppressant therapy. Although attractive as a non-invasive technique, this approach did not prove to be useful in stable patients. More and larger studies are needed to address the relevance of these viruses on IBD course, in stable patients and during exacerbations.

Asymptomatic reactivation of hepatitis B virus after prolonged treatment with etanercept.

Etanercept is an anti-tumor necrosis factor ɑ (anti-TNFɑ) drug used for treating immunomediated inflammatory diseases. It is least associated with hepatitis B virus (HBV) reactivation. We present a 71-year-old man with psoriasis refractory to phototherapy and acitretin, which led to etanercept monotherapy. Before anti-TNFɑ treatment, past contact with HBV was elicited; antibodies to HBc and HBs were positive whereas HBsAg was negative. Seven years after treatment initiation, while the patient was completely asymptomatic, a transaminase elevation was found and a reactivation of HBV was documented, with a high viral load of the virus. He started entecavir therapy and, after a 14-month follow-up, the viral load is still detectable at a low level, as well as HBsAg. We emphasize the late and asymptomatic reactivation of HBV associated with soluble anti-TNFɑ monotherapy. This case reinforces the importance of current recommendations for periodic monitoring of viral load and HBV markers in all patients that have had prior contact with HBV (positive anti-HBc), with or without indication for treatment of HBV (HBsAg and HBV-DNA negative).