Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study.

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.

Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Prevalence of etravirine resistance associated mutations in HIV-1 strains isolated from infected individuals failing efavirenz: comparison between subtype B and non-B genetic variants.

Etravirine (ETR) is a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) with a high genetic barrier to the development of resistance and with potential activity against Human immunodeficiency virus type 1 (HIV-1) strains resistant to first-generation NNRTIs. The objective of this study was to investigate the prevalence of ETR resistance associated mutations (RAMs) in HIV-1 strains isolated from infected individuals failing efavirenz (EFV), as well as to evaluate possible differences in the distribution of ETR RAMs between subtype B and non-B genetic variants. Nucleotide sequences of the protease and partial reverse transcriptase (RT) coding regions of the pol gene of 55 HIV-1 strains isolated from infected individuals failing EFV on regular follow-up at a reference center in Portugal, were retrospectively analyzed. The most prevalent ETR RAMs observed were L100I, V90I, and K101E, with a prevalence of 16.4% (n = 9), 9.1% (n = 5), and 5.5% (n = 3), respectively. Overall, 47.3% (n = 26) of the nucleotide sequences had at least one ETR RAM: 38.2% (n = 21) had one ETR RAM, 7.3% (n = 4) had two ETR RAMs and 1.8% (n = 1) had three ETR RAMs. No statistically significant differences were found in the distribution of ETR RAMs between subtype B and non-B genetic variants. The results demonstrate that ETR rescue therapy is a viable option in treatment-experienced individuals failing EFV and suggests that ETR may be equally useful in HIV-1 infections caused by different genetic variants.

Occult hepatitis B infection by a recombinant D/C virus in an immunosuppressed patient.

Approximately 300 million people worldwide were living with chronic hepatitis B virus infection as of 2016, however, this number does not account for those who might be living with occult hepatitis B virus infection due to difficulty diagnosing this condition. The multiple genotypes and the ability of the hepatitis B virus to acquire mutations that down-regulate its expression make occult hepatitis B virus infection a very elusive diagnosis. This is especially worrisome when there is a need to start immunosuppressive therapies, since there is a risk of reactivation in undiagnosed patients. We present a case of female patient who was referred to the consultation because she was about to start chemotherapy with an anti-CD20 agent and had a positive anti-HBc and anti-HBs. During routine workup an occult hepatitis B virus infection was diagnosed. Upon further study mutations in the PreCore and Basal Core Promoter regions were identified, as well as, a double genotype D/C. Therapy with tenofovir was initiated before the patient was started on chemotherapy. This case highlights the importance of comprehensive studying of patients who present with apparently resolved chronic hepatitis B virus infection, especially when they are about to start immunosuppressive therapies.

Mycobacterium chimaera Disseminated Infection.

The incidence and prevalence of nontuberculous mycobacterial disease is increasing due to enhanced clinician awareness and improved detection methods. The species identification using molecular microbiology techniques allows a better understanding of the differences in pathogenicity and treatment response. A 57-year-old man with a history of B-cell lymphoma in remission was transferred from the hematology department due to fever of unknown origin, night sweats and asthenia. The empirical antibiotic therapy was initiated with no clinical response, and he developed a subacute pneumonia, severe anemia and hepatosplenomegaly. After positive blood, bronchoalveolar lavage and bone marrow cultures, a disseminated Mycobacterium avium-intracellulare complex infection was diagnosed, and the patient began treatment with clarithromycin, rifabutin and ethambutol. Two weeks later, a fourth antibiotic was added, amikacin at first and then linezolid, with slow but gradual improvement. Due to amikacin-related severe kidney injury and linezolid-related severe myelosuppression, the fourth antibiotic was changed to moxifloxacin, which the patient tolerated. After 6 months of therapy, the sensitivity to the regimen was confirmed and the species was identified as Mycobacterium chimaera (MC), using the molecular genetic test GenoType NTM-DR. The blood and tissue cultures were negative after 4 months of therapy, and treatment was continued for 12 months. Although the infection was being treated successfully, the patient's B-cell lymphoma relapsed after 12 months and the patient died. This is a case report of a confirmed severe and disseminated MC infection in an immunocompromised patient using a molecular genetic test, successfully treated using a four-drug regimen.

Acute retinal necrosis by herpes simplex virus type 1: an unusual presentation of a primary infection.

Herpes simplex virus (HSV) can affect the central nervous system causing meningitis, encephalitis and, rarely, acute retinal necrosis. We present a case of a 46-year-old man, previously healthy complaining of a 5-day persistent headache and sudden loss of vision of his left eye that progressed to the right. We started ceftriaxone, methylprednisolone and acyclovir for suspected encephalitis with vasculitis. HSV-1 was identified in vitreous and aqueous humour. Therapy with acyclovir was maintained and two intravitreous boluses of foscarnet were administered, without improvement. Usually being a benign infection, HSV can, in rare cases like this, have catastrophic effects in the optic tract.

Prevalence of Hepatitis A Virus Antibody in Portuguese Travelers: A New Paradigm.

INTRODUCTION: In Portugal, the prevalence of hepatitis A virus infection has decreased in the past decades, especially in young adults. The aim of this study was to detect the prevalence of antibody to hepatitis A virus in a population observed in our Travel Clinic. MATERIAL AND METHODS: Antibodies against hepatitis A, hepatitis B, hepatitis C and human immunodeficiency virus were tested using standard enzyme immunoassay in patients older than 18. The exclusion criteria were: prior vaccination for hepatitis A virus, previous diagnosis of infection with hepatitis B virus, hepatitis C virus and/or human immunodeficiency virus, foreign travelers and long-term expatriates. We applied an epidemiological survey and data was statistically analyzed with SPSS® 18.0. RESULTS: In the 665 travelers studied, natural immunity to hepatitis A virus was present in 57.6% (n = 383). They were stratified into 8 age groups and for each one hepatitis A immunity was clarified: 5.0% (n = 1) in 18 - 25 years, 32.3% (n = 21) in 26 - 30 years, 40.9% (n = 47) in 31 - 35 years, 45.8% (n = 54) in 36 - 40 years, 68.7% (n = 79) in 41 - 45 years, 70.1% (n = 68) in 46 - 50 years, 80.8% (n = 63) in 51 - 55 years and 87.7% (n = 50) over 56 years old. In those who accepted further screening, positivity for hepatitis B core antibody was found in 0.6% (n = 3) travelers, hepatitis C virus infection in 1.1% (n = 6) and human immunodeficiency virus infection in 0.5% (n = 3) whose previous status was unknown. The most frequent travel destination was sub-Saharan Africa (72.6%; n = 483). DISCUSSION: We found 49.1% (n = 260) travelers under 50 years old susceptible to hepatitis A virus infection and for those between 40 and 50 years, 30.7% (n = 65) still need vaccine protection. CONCLUSION: Across age groups there is a trend towards lower prevalence of hepatitis A virus antibody, in particular among youngsters, when compared with older Portuguese studies.

Introdução: A prevalência da hepatite A em Portugal tem diminuído nas últimas décadas, sobretudo nos jovens adultos. O objetivo deste estudo foi avaliar a prevalência do anticorpo contra o vírus da hepatite A numa população que recorreu à consulta de Medicina do Viajante. Material e Métodos: Avaliamos a serologia de hepatite A, hepatite B, hepatite C e do vírus da imunodeficiência humana, através de imunoensaio enzimático padrão, de viajantes com idade igual ou superior a 18 anos. Excluímos aqueles previamente vacinados contra o vírus da hepatite A, com diagnóstico prévio de infeção pelos vírus da hepatite B, hepatite C e/ou vírus da imunodeficiência humana, estrangeiros e emigrantes. Aplicamos um inquérito epidemiológico prospetivo e analisamos os dados estatisticamente com o SPSS® versão 18. Resultados: Participaram no estudo 665 viajantes, dos quais 57,6% (n = 383) eram imunes para o vírus da hepatite A. Foram estratificados por oito grupos etários e, para cada um, foi avaliada a presença de imunidade: 5,0% (n = 1) nos 18 - 25 anos, 32,3% (n = 21) nos 26 - 30 anos, 40,9% (n = 47) nos 31 - 35 anos, 45,8% (n = 54) nos 36 - 40 anos, 68,7% (n = 79) nos 41 - 45 anos, 70,1% (n = 68) nos 46 - 50 anos, 80,8% (n = 63) nos 51 - 55 anos e 87,7% (n = 50) com idade igual ou superior a 56 anos. Dos que aceitaram realizar rastreio, detetou-se o anticorpo hepatitis B core em 0,6% (n = 3) viajantes, infeção pelo vírus da hepatite C em 1,1% (n = 6) e pelo vírus da imunodeficiência humana em 0,5% (n = 3), cujos estados serológicos eram desconhecidos. O destino mais frequente foi a África Subsariana (72,6%; n = 483). Discussão: Detetamos 49,1% (n = 260) viajantes suscetíveis a infeção pelo vírus da hepatite A e o grupo dos 40 aos 50 anos de idade, 30,7% (n = 65) ainda necessita de proteção vacinal. Conclusão: A prevalência do anticorpo contra o vírus da hepatite A tem diminuindo na população Portuguesa, aumentando a suscetibilidade a esta infeção nas deslocações a áreas endémicas.

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

Hemiballistic movements in a newly HIV patient.

Infections of central nervous system (CNS) include a broad group of conditions and pose a particular challenge to physicians, especially in immunocompromised individuals. This case refers to a 26-year-old male patient with a history of smoked hashish and drug abuse admitted to the infectious disease department with hemiballismus of left hemibody and a positive HIV serologic test. A magnetic resonance imaging (MRI) study showed lesions at lower left and right cerebellar hemisphere, one of them thalamus - mesencephalic suggesting an opportunistic infection or an HIV associated encephalopathy. Lumbar puncture, brain biopsy and successive neuroimaging were not conclusive for one disease and despite the use of directed therapy for cerebral toxoplasmosis, meningeal tuberculosis, anti-retrovirals and sedative medication, after over 6 weeks of hospitalization pallidotomy was performed. After 5 months of oral and surgical treatment the patient showed clinical, immunological and radiological recovery.

Gastritis as a manifestation of primary CMV infection in an immunocompetent host.

The cytomegalovirus (CMV) disease spectrum is very wide, with symptomatic infections being rare in immunocompetent hosts. We present the case of a 31-year-old immunocompetent man diagnosed with CMV gastritis in the context of primary infection. The most important laboratory abnormalities leading to diagnosis were: elevation of liver enzymes (3-4× the upper limit of normal), thrombocytopenia (133 G/L), lymphocytosis (55%-4.2 G/L) with activated lymphocytes, CMV IgM positive (negative IgG), CMV viral load of 5700 copies/mL (real-time PCR); autoimmunity study showed antiparietal cell antibodies; abdominal ultrasonography detected homogenous splenomegaly (14.6×13.4 cm) and endoscopy unveiled superficial erosions of the gastric antrum that were biopsied. Anatomopathology and immunohistochemistry of the samples identified cytomegalic inclusions in endothelial cells. Cellular and humoral immunity deficits were excluded. As the patient developed severe asthaenia, adynamia and epigastric pain, he was administered gancyclovir 5 mg/kg intravenously twice daily for 7 days, with resolution of symptoms and gastric lesions confirmed by re-evaluation through endoscopy.

[Acute bacterial meningitis as an occupational disease]. / Meningite bacteriana aguda como doença ocupacional.

Streptococcus suis is a zoonotic pathogen with worldwide distribution, responsible for more than 700 human cases globally reported. This infection affects mostly men, exposed to pig or pork, which leads to its usual classification as an occupational disease. We report a case of acute bacterial meningitis in a 44 years old male. According to his past medical history, the patient had chronic alcoholism and worked in a restaurant as a piglet roaster. Microbiological examination of blood and CSF revealed S. suis. After 14 days of ceftriaxone the patient fully recovered. The authors review the clinical reports previously described in Portugal. In all of them was possible to identify risk exposition to pork. We alert to this microorganism's importance in Portugal where it is probably underdiagnosed.

Streptococcus suis é um agente zoonótico com distribuição mundial, atualmente responsável por mais de 700 casos reportados em humanos. Atinge quase em exclusivo indivíduos do sexo masculino com exposição a suínos ou à sua carne, classificando-se neste contexto como uma doença ocupacional. Os autores apresentam um caso de meningite bacteriana aguda por este agente infeccioso, num homem de 44 anos com antecedentes de etilismo crónico cuja atividade profissional consistia em assar leitões num restaurante. A análise microbiológica do sangue e do LCR revelou S. suis, agente etiológico desta infecção. Foi tratado empiricamente com ceftriaxona, completando 14 dias de antibioterapia com resolução total do quadro. Reveem-se os casos previamente descritos em Portugal. Em todos foi possível identificar exposição a carne de porco crua. Alerta-se para a importância deste agente infeccioso em Portugal, onde possivelmente se encontrará sub-diagnosticado.

Angola's 2013 dengue outbreak: clinical, laboratory and molecular analyses of cases from four Portuguese institutions.

INTRODUCTION: Dengue virus (DENV) is the arbovirus with the widest impact on human health. In Africa in general, and in Angola in particular, the epidemiology and public health impact of DENV is far from clear. However, rapid population growth, unplanned urbanization, increased international travel, and the presence of virus major vector (Aedes aegypti) in the country suggest that DENV transmission may occur. METHODOLOGY: In parallel to the occurrence of a dengue outbreak affecting the capital of Angola, between March and July 2013 four Portuguese institutions diagnosed dengue infection in 146 individuals returning to Portugal. Clinical presentation, laboratory findings, and molecular analyses of partial viral genomic segments were performed. RESULTS: The mean age of the individuals included in this study was 42 years old, the majority being men of Portuguese nationality, reporting various lengths of stay in Angola. Fever was the most reported clinical sign, being frequently associated (61.0%) with myalgia and headache. Hematological values, including hematocrit, white-blood cell and platelets counts, correlated with the absence of severe or complicated cases, or coagulation disorders. No deaths were observed. Viral NS1 was detected in 56.2% of the samples, and all NS1 negative cases had anti-dengue IgM antibodies. RT-PCR indicated the presence of DENV1, which was confirmed by phylogenetic analysis of 25 partial NS5 viral sequences. CONCLUSION: The DENV cases analyzed conformed to classical and uncomplicated dengue, caused by the suggested exclusive circulation of a genetically homogeneous DENV1 of genotype III, apparently with a single origin.

Detection of the protease codon 35 amino acid insertion in sequences from treatment-naïve HIV-1 subtype C infected individuals in the Central Region of Portugal.

BACKGROUND: Amino acids insertions in the protease (PR) coding region have been reported in protease inhibitors (PIs) treatment-naïve and experienced HIV-1 infected individuals ranging from 0.1% to 4.55% and have been rarely found in non-B HIV-1 subtype strains. OBJECTIVES: To investigate the presence of amino acid insertions in the PR coding region in sequences from treatment-naïve HIV-1 infected individuals in the Central Region of Portugal. STUDY DESIGN: Sequences of the pol gene from 260 treatment-naïve HIV-1 infected individuals between 2000 and 2008 were analyzed and phylogenetic analysis was performed. RESULTS: A threonine insertion (E35E_T) was detected in 2.69% (n=7) of the sequences analyzed and all the sequences that possessed this insertion were identified as subtype C. All the seven inserted sequences clustered in the same lineage of the phylogenetic tree. Heterosexual and intravenous drug use were found to be the routes of infection. No major mutations in the PR coding region associated with resistance to PIs were detected. CONCLUSIONS: It was found the highest prevalence of PR codon 35 insertion among treatment-naïve HIV-1 infected individuals ever reported in the western countries. Epidemiological data and Phylogenetic analysis indicated the possibility of transmission of this insertion. The results suggested that these inserted strains have normal susceptibility to PIs containing regimens. This study demonstrated the spreading epidemic of PR codon 35 inserted strains from subtype C in the Central Region of Portugal, during the past eight years.