[Use of ribavirin in viruses other than hepatitis C. A review of the evidence]. / Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia.

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.

[Diagnosis and treatment of imported malaria in Spain: Recommendations from the Malaria Working Group of the Spanish Society of Tropical Medicine and International Health (SEMTSI)]. / Diagnóstico y tratamiento de la malaria importada en España: recomendaciones del Grupo de Trabajo de Malaria de la Sociedad Española de Medicina Tropical y Salud Internacional (SEMTSI).

Malaria is a common parasitic disease diagnosed in the returned traveler. Mortality in travelers with imported malaria is around 2-3%, and one of the main factors associated with poor prognosis is the delay in the diagnosis and treatment. Imported malaria cases usually present with fever, headache and myalgia, but other symptoms may appear. The diagnosis should be performed as soon as possible, using thick smear or rapid diagnostic tests, and a blood smear. Treatment should be initiated urgently. In cases of severe malaria, the use of intravenous artemisinins has proved to be superior to intravenous quinine. This document reviews the recommendations of the expert group of the Spanish Society of Tropical Medicine and International Health (SEMTSI) for the diagnosis and treatment of imported malaria in Spain.

Comparison of imported Plasmodium ovale curtisi and P. ovale wallikeri infections among patients in Spain, 2005-2011.

Sequencing data from Plasmodium ovale genotypes co-circulating in multiple countries support the hypothesis that P. ovale curtisi and P. ovale wallikeri are 2 separate species. We conducted a multicenter, retrospective, comparative study in Spain of 21 patients who had imported P. ovale curtisi infections and 14 who had imported P. ovale wallikeri infections confirmed by PCR and gene sequencing during June 2005-December 2011. The only significant finding was more severe thrombocytopenia among patients with P. ovale wallikeri infection than among those with P. ovale curtisi infection (p = 0.031). However, we also found nonsignificant trends showing that patients with P. ovale wallikeri infection had shorter time from arrival in Spain to onset of symptoms, lower level of albumin, higher median maximum core temperature, and more markers of hemolysis than did those with P. ovale curtisi infection. Larger, prospective studies are needed to confirm these findings.

Performance of a new gelled nested PCR test for the diagnosis of imported malaria: comparison with microscopy, rapid diagnostic test, and real-time PCR.

Microscopy and rapid diagnostic tests (RDTs) are the techniques commonly used for malaria diagnosis but they are usually insensitive at very low levels of parasitemia. Nested PCR is commonly used as a reference technique in the diagnosis of malaria due to its high sensitivity and specificity. However, it is a cumbersome assay only available in reference centers. We evaluated a new nested PCR-based assay, BIOMALAR kit (Biotools B&M Labs, Madrid, Spain) which employs ready-to-use gelled reagents and allows the identification of the main four species of Plasmodium. Blood samples were obtained from patients with clinical suspicion of malaria. A total of 94 subjects were studied. Fifty-two (55.3%) of them were malaria-infected subjects corresponding to 48 cases of Plasmodium falciparum, 1 Plasmodium malariae, 2 Plasmodium vivax, and 1 Plasmodium ovale. The performance of the BIOMALAR test was compared with microscopy, rapid diagnostic test (RDT) (BinaxNOW® Malaria) and real-time quantitative PCR (qPCR). The BIOMALAR test showed a sensitivity of 98.1% (95% confidence interval [CI], 89.7-100), superior to microscopy (82.7% [95% CI, 69.7-91.8]) and RDT (94.2% [95% CI, 84.1-98.8]) and similar to qPCR (100% [95% CI, 93.2-100]). In terms of specificity, the BIOMALAR assay showed the same value as microscopy and qPCR (100% [95% CI, 93.2-100]). Nine subjects were submicroscopic carriers of malaria. The BIOMALAR test identified almost all of them (8/9) in comparison with RDT (6/9) and microscopy (0/9). In conclusion, the BIOMALAR is a PCR-based assay easy to use with an excellent performance and especially useful for diagnosis submicroscopic malaria.

[Etravirine in clinical practice: Experience in 151 non-naïve patients]. / Etravirina en la práctica clínica: experiencia de uso en 151 pacientes pretratados.

BACKGROUND: There are limited data on etravirine (ETV) use in routine clinical practice. METHODS: The reasons, efficacy and tolerability of its use are retrospectively reviewed. RESULTS: Overall, 151patients started a regimen containing ETV. The main reasons for prescription were toxicity and virological failure. After a median follow-up of 16months 76.2% of the patients had an undetectable viral load. Patients with detectable HIV-RNA at baseline had a greater risk of failure (31.7% vs 18%; P=.05). CONCLUSION: ETV is safe, effective and durable.

Application of telemedicine in infectious diseases.

INTRODUCTION: Infectious pathologies can benefit from the application of Telemedicine (TM). This study provides a description of the infectious pathology treated by the Telemedicine Service of the Hospital Central de la Defensa Gómez Ulla (STM-HCDGU). METHODS: Analysis of the e-consultations made by members of the Armed Forces (FA) of Spain displaced to the area of ​​operations (ZO) in the period between 01/1/2015 and 31/12/2018 who developed infectious symptoms. RESULTS: 127 infectious diseases were diagnosed, the most frequent being those of respiratory etiology and later malaria. Geographically Africa and embarked contingents were the most significant. It was necessary to evacuate 18 patients to the HCDGU, being the diagnosis of malaria the most frequent reason for evacuation, cause of the only fatal case. CONCLUSIONS: infectious diseases benefit from the application of TM, being an important tool for the diagnosis and treatment of these, constituting an opportunity to expand to other displaced or remote populations.

The Impact of Antibiotic Prophylaxis on a Retrospective Cohort of Hospitalized Patients with COVID-19 Treated with a Combination of Steroids and Tocilizumab.

OBJECTIVES: In the context of COVID-19, patients with a severe or critical illness may be more susceptible to developing secondary bacterial infections. This study aims to investigate the relationship between the use of prophylactic antibiotic therapy and the occurrence of bacterial or fungal isolates following the administration of tocilizumab in hospitalized COVID-19 patients who had previously received steroids during the first and second waves of the pandemic in Spain. METHODS: This retrospective observational study included 70 patients hospitalized with COVID-19 who received tocilizumab and steroids between January and December 2020. Data on demographics, comorbidities, laboratory tests, microbiologic results, treatment, and outcomes were collected from electronic health records. The patients were divided into two groups based on the use of antibiotic prophylaxis, and the incidence of bacterial and fungal colonizations/infections was analyzed. RESULTS: Among the included patients, 45 patients received antibiotic prophylaxis. No significant clinical differences were observed between the patients based on prophylaxis use regarding the number of clinically diagnosed infections, ICU admissions, or mortality rates. However, the patients who received antibiotic prophylaxis showed a higher incidence of colonization by multidrug-resistant bacteria compared to that of the subgroup that did not receive prophylaxis. The most commonly isolated microorganisms were Candida albicans, Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus epidermidis. Conclusions: In this cohort of hospitalized COVID-19 patients treated with tocilizumab and steroids, the use of antibiotic prophylaxis did not reduce the incidence of secondary bacterial infections. However, it was associated with an increased incidence of colonization by multidrug-resistant bacteria.

Imported submicroscopic malaria in Madrid.

BACKGROUND: Submicroscopic malaria (SMM) can be defined as low-density infections of Plasmodium that are unlikely to be detected by conventional microscopy. Such submicroscopic infections only occasionally cause acute disease, but they are capable of infecting mosquitoes and contributing to transmission. This entity is frequent in endemic countries; however, little is known about imported SMM.The goals of this study were two-fold: a) to know the frequency of imported SMM, and b) to describe epidemiological, laboratorial and clinical features of imported SMM. METHODS: A retrospective study based on review of medical records was performed. The study population consisted of patients older than 15 years attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1, 2002 and December 31, 2007. Routinely detection techniques for Plasmodium included Field staining and microscopic examination through thick and thin blood smear. A semi-nested multiplex malaria PCR was used to diagnose or to confirm cases with low parasitaemia. RESULTS: SMM was diagnosed in 104 cases, representing 35.5% of all malaria cases. Mean age (IC95%) was 40.38 years (37.41-43.34), and sex distribution was similar. Most cases were in immigrants, but some cases were found in travellers. Equatorial Guinea was the main country where infection was acquired (81.7%). Symptoms were present only in 28.8% of all SMM cases, mainly asthenia (73.3% of symptomatic patients), fever (60%) and arthromialgias (53.3%). The associated laboratory abnormalities were anaemia (27.9%), leukopaenia (15.4%) and thrombopaenia (15.4%). Co-morbidity was described in 75 cases (72.1%). CONCLUSIONS: Results from this study suggest that imported SMM should be considered in some patients attended at Tropical Medicine Units. Although it is usually asymptomatic, it may be responsible of fever, or laboratory abnormalities in patients coming from endemic areas. The possibility of transmission in SMM has been previously described in endemic zones, and presence of vector in Europe has also been reported. Implementation of molecular tests in all asymptomatic individuals coming from endemic area is not economically feasible. So re-emergence of malaria (Plasmodium vivax) in Europe may be speculated.

Application of telemedicine in infectious diseases. / Aplicación de la telemedicina en enfermedades infecciosas.

INTRODUCTION: Infectious pathologies can benefit from the application of Telemedicine (TM). This study provides a description of the infectious pathology treated by the Telemedicine Service of the Hospital Central de la Defensa Gómez Ulla (STM-HCDGU). METHODS: Analysis of the e-consultations made by members of the Armed Forces of Spain displaced to the area of operations in the period between 01/1/2015 and 31/12/2018 who developed symptoms of infectious diseases. RESULTS: 127 infectious diseases were diagnosed, the most frequent being those of respiratory etiology and later malaria. Geographically Africa and embarked contingents were the most significant. It was necessary to evacuate 18 patients to the HCDGU, being the diagnosis of malaria the most frequent reason for evacuation, cause of the only fatal case. CONCLUSIONS: infectious diseases benefit from the application of TM, being an important tool for the diagnosis and treatment of these, constituting an opportunity to expand to other displaced or remote populations.

Incidence, Characteristics, Laboratory Findings and Outcomes in Acro-Ischemia in COVID-19 Patients.

AIM: In addition to its respiratory impact of SARS-CoV2, skin lesions of probable vascular origin have been described. This study intends to quantify the incidence of acro-ischemic lesions in COVID-19 infected adult subjects in our population, describing clinical patterns and associated findings. METHODS: All adult confirmed cases of COVID-19 infection who presented with acro-ischemic lesions and received care in our institution were prospectively enrolled up to May 15th, 2020. The variables included demographics, comorbidities, analytical parameters, clinical presentations and COVID-19 treatment. RESULTS: We enrolled 24 patients. The overall rate of acro-ischemic findings in COVID-19 patients was 1.2% [0.6% for outpatients and 2.9% for hospitalized (ICU and non-ICU patients)], but the observed incidence for acro-ischemia in ICU patients was remarkably higher (23.0%, p<0.001). We have described four different clinical patterns of acroischemia: atypical Raynaud´s phenomenon (ARP), (4); pseudo-pernio (PP), (5); severe microcirculatory ischemia with preserved pulse (SMI), (6); and dry gangrene with arteriosclerosis obliterans (AO), (9). Kendall´s τ correlation with lung disease severity was 0.877 (95% CI, 0.756 to 0.968); p<0.01). ARP individuals were predominantly female, while SMI appeared lately in elderly hospitalized subjects with better prognosis. AO occurred in patients with more comorbidity and younger than those with SMI. We observed other associated lesions of suggestive ischemic nature in other organs in all groups (15 patients of total sample). Plasma procalcitonin was significantly higher in patients who developed SMI (median and interquartile range: 9.99 (4.2, 12.3) mg/mL vs 0.26 (0.11, 0.89) mg/mL; p<0.001), and D-dimer level at hospital admission was significantly higher in AO patients (median and interquartile range: 1166 (1050, 2111) mg/L vs 502 (448, 777) mg/L; p<0.001). CONCLUSION: The observed risk for acroischemia in COVID-19 is high in ICU patients (23%). We have described four different clinical patterns of acroischemia (ARP, PP, SMI and AO) associated with lung disease severity. Authors have communicated various lesions of suggestive ischemic nature in other organs. Raynaud-like pattern is reported as a "novelty".

Loiasis in sub-Saharan migrants living in Spain with emphasis of cases from Equatorial Guinea.

BACKGROUND: Loiasis is an uncommon and poorly understood parasitic disease outside endemic areas of Africa. The aim of this study was to describe the clinical and biological patterns and treatment of imported loiasis by sub-Saharan migrants diagnosed in Madrid, Spain. METHODS: A retrospective study was conducted with sub-Saharan immigrants seen at the Tropical Medicine Unit of the Carlos III Hospital in Madrid, Spain, a reference center, over 19 years. Categorical variables were expressed as frequency counts and percentages. Continuous variables were expressed as the mean and standard deviation (SD) or median and interquartile range (IQR: Q3-Q1). Chi-square tests were used to assess the association between categorical variables. The measured outcomes were expressed as the odds ratio (OR) with a 95% confidential interval. Continuous variables were compared by Student's t-tests or Mann-Whitney U tests. Binary logistic regression models were used. P <  0.05 was considered a statistically significant difference. RESULTS: One hundred thirty-one migrants from tropical and subtropical areas with loiasis were identified. Forty-nine patients were male (37.4%). The migrants' mean age (±SD) was 42.3 ± 17.3 years, and 124 (94.7%) were from Equatorial Guinea. The median time (IQR) between arrival in Spain and the first consultation was 2 (1-7) months. One hundred fifteen migrants had eosinophilia, and one hundred thirteen had hyper-IgE syndrome. Fifty-seven patients had pruritus (43.5%), and thirty patients had Calabar swelling (22.9%). Seventy-three patients had coinfections with other filarial nematodes (54.2%), and 58 migrants had only Loa loa infections (45.8%). One hundred two patients (77.9%) were treated; 45.1% (46/102) patients were treated with one drug, and 54.9% (56/102) patients were treated with combined therapy. Adverse reactions were described in 14 (10.7%) migrants. CONCLUSIONS: Our patients presented early clinical manifestations and few atypical features. Thus, physicians should systematically consider loiasis in migrants with a typical presentation. However, considering that 72.5% of the patients had only positive microfilaremia without any symptoms, we suggest searching for microfilaremia in every migrant from endemic countries for loiasis presenting with eosinophilia.

[Malignancies in HIV infected patients: study of 139 cases]. / Tumores en pacientes con infección por el virus de la inmunodeficiencia humana: estudio de 139 casos.

BACKGROUND AND OBJECTIVE: Since the introduction of highly active antiretroviral therapy (HAART), the natural history of HIV infection has been altered by an increasing survival. Following this, neoplastic diseases have become more common in HIV positive patients. The purpose of this study was to describe the types of tumor, clinical features and prognosis of HIV infected patients with malignant diseases. PATIENTES AND METHODS: A descriptive study of epidemiological and clinical features was undertaken at Hospital Carlos III, in Madrid. Information was collected on age, sex, risk factors for HIV, HBV/HCV coinfection, malignancies, diagnosis of AIDS, viral load and CD4 cell counts at diagnosis, antiretroviral therapy and mortality. A total of 139 HIV-infected patients were identified who had at least one malignancy. Statistical analysis was performed using SPSS 15.0 package. RESULTS: Types of malignancy were Kaposi's Sarcoma (n=43, 30.9%); non-Hodgkin lymphoma (n=42, 30.2%); gynecologic malignancy (n=16, 11.5%); Hodgkin's disease (n=15, 10.8%); hepatocellular carcinoma (n=7, 5%) and others (n=16, 11.5%). Mean age at diagnosis was 40 years (IC 95% 38.51-1.50). Male/female ratio was 3.63. Patients with HBV or HCV coinfection were 1.4% and 35.3% respectively. Risk factor for HIV was MSM (n=64;46%), IDUs (n=48; 34.5%) and heterosexual (n=26; 18.7%). Viral load was undetectable in 27 cases (19.4%); CD4 cell count was<200 cell/mcl in 58 cases (41.7%). There were 77 (55.4%) patients on HAART when cancer was diagnosed. Mean time on HAART was 23.31 months. Ten patients (7.2%) developed a secondary tumor. Twelve years survival was 20%. CONCLUSIONS: Increased survival of HIV-infected patients receiving HAART makes it possible the development of secondary tumors and AIDS- unrelated malignancies, sometimes related to another virus.

Use of ribavirin in viruses other than hepatitis C. A review of the evidence. / Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia.

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitisC virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.

[Immigration and HIV: pulmonary, cutaneous and genitourinary syndromes. Eosinophilia]. / Inmigración y VIH: síndromes pulmonar, cutáneo y genitourinario. Eosinofilia.

Infectious diseases are the leading cause of mortality in less developed countries, many of which are located in tropical areas. These diseases have particular features than can hamper diagnosis unless clinicians are familiar with their characteristics. The present article describes the clinical pattern of pulmonary, cutaneous and genitourinary tropical diseases and the main principles of their diagnosis. Emphasis is placed on their geographical distribution and the influence of HIV infection.

HIV and malaria.

Malaria and HIV infection are both prevalent in the areas of the world where these diseases have the largest burden. Both diseases interact with one another and this interaction is especially important in areas with non-continuous malaria transmission, in pregnant women, and in patients with more severe immunodeficiency. Malaria has been implicated in transitory higher viral load and in low CD4 counts, so it could have an influence on higher transmission rates of HIV and perhaps in the course of HIV infection. Infection with HIV has been shown to cause more clinical malaria and higher parasitemia in patients living in perennial transmission areas, and higher rates of severe malaria episodes and mortality in areas where malaria is transmitted with seasonal frequency. The HIV-infected patients have also higher rates of malaria treatment failures. Co-trimoxazole prophylaxis has been shown to be effective in the prevention of some opportunistic infections in HIV-infected patients, but also in prevention of malaria episodes. Antiretroviral protease inhibitors demonstrate antimalarial effects that could have important clinical and therapeutic implications. For all of these reasons, HIV and malaria should be considered together as part of healthcare programs for both diseases in countries where their co-presence favors an interaction with important clinical consequences.

Immunizations in HIV-infected adults.

The incidence or severity of certain vaccine-preventable diseases is higher in HIV-infected individuals. However, immune responses to vaccination may be diminished, particularly in those with severe immunosuppression. Higher doses of vaccine, more frequent boosters, or revaccination after antiretroviral therapy-induced immune reconstitution are strategies to be considered for patients in certain circumstances. In addition, some vaccines may be harmful when given to severely immunocompromised patients. The challenge for healthcare providers is assessing the safety and effectiveness of vaccines for HIV-infected patients, especially when information on vaccines has not been fully characterized in the HIV-setting. This review presents state-of-the-art knowledge about immunizations for HIV-adults. The efficacy and safety of current vaccines, their current indications in HIV-infected adults, and the strategies aimed to enhance their results are discussed.

Dermatological manifestations in onchocerciasis: A retrospective study of 400 imported cases.

INTRODUCTION: Onchocerciasis is caused by Onchocerca volvulus and mainly leads to pruritus and skin and visual disorders, including blindness. Seventeen million people are infected in 38 countries; 31 of these are in sub-Saharan Africa, six in Latin America and one on the Arabian Peninsula. More than 99% of cases occur in sub-Saharan Africa where 120 million people are at risk of infection. Eye disorders have been well-documented; however, skin disorders have not been described accurately. The objective of our study was to describe the epidemiology, main skin manifestations and treatment of imported onchocerciasis. MATERIAL AND METHODS: A retrospective study was thus conducted by analysing the main demographic, clinical and treatment data regarding a cohort of 400 patients attending a reference clinical unit over a 17-year period. RESULTS: Most patients were female (55%) with mean age 37.5±16.7 years. All the migrants came from sub-Saharan countries. The most frequently occurring dermatological symptom was pruritus. Ivermectin had been used as first-line therapy and adverse reactions had been described in 11 patients (3.2%). CONCLUSIONS: The results indicate the fact that there should be a clinical suspicion of onchocerciasis regarding immigrants from endemic areas having skin lesions compatible with the disease's profile or asymptomatic patients having eosinophilia or unexplained high IgE. Moreover, skin snips from the buttocks region were very fruitful and treatment with ivermectin was seen to be safe. This is the largest case series regarding imported onchocerciasis described up to the present time.

Executive summary of imported infectious diseases after returning from foreign travel: Consensus document of the Spanish Society for Infectious Diseases and Clinical Microbiology (SEIMC).

In a global world, knowledge of imported infectious diseases is essential in daily practice, both for the microbiologist-parasitologist and the clinician who diagnoses and treats infectious diseases in returned travelers. Tropical and subtropical countries where there is a greater risk of contracting an infectious disease are among the most frequently visited tourist destinations. The SEIMC considers it appropriate to produce a consensus document that will be useful to primary care physicians as well as specialists in internal medicine, infectious diseases and tropical medicine who help treat travelers returning from tropical and sub-tropical areas with infections. Preventive aspects of infectious diseases and infections imported by immigrants are explicitly excluded here, since they have been dealt with in other SEIMC documents. Various types of professionals (clinicians, microbiologists, and parasitologists) have helped produce this consensus document by evaluating the available evidence-based data in order to propose a series of key facts about individual aspects of the topic. The first section of the document is a summary of some of the general aspects concerning the general assessment of travelers who return home with potential infections. The main second section contains the key facts (causative agents, diagnostic procedures and therapeutic measures) associated with the major infectious syndromes affecting returned travelers [gastrointestinal syndrome (acute or persistent diarrhea); febrile syndrome with no obvious source of infection; localized cutaneous lesions; and respiratory infections]. Finally, the characteristics of special traveler subtypes, such as pregnant women and immunocompromised travelers, are described.

Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients.

Surveillance of drug resistance mutations in antiretroviral-experienced HIV(+) patients may provide useful information regarding options available for rescue interventions. All resistance tests performed from 1999 to 2005 on antiretroviral-experienced individuals at one reference laboratory in Madrid were examined. Only mutations associated with drug resistance recorded at the September 2006 IAS-USA list were considered. A total of 2137 specimens were analyzed. Overall, 71.1% showed resistance mutations to at least one drug class, 56.1% to at least two, and 21% to all three drug families. Resistance mutations were 65% for NRTI, 44.4% for NNRTI, and 42.5% for PI. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. Their rate significantly declined since 1999. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). The presence of five or more was 58.8% in 1999 but declined to 22.2% in 2005. The rate of drug resistance mutations causing NRTI and PI resistance has steadily declined in antiretroviral-experienced patients since 1999. The availability of a large number and/or more convenient NRTI as well as the wide use of ritonavir-boosted PI could explain these observations. However, broad PI cross-resistance was seen in nearly 25% of antiretroviral-experienced patients in 2005. Therefore, there is a still need for new antiretrovirals with different resistance profiles.