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.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

Travel-associated human trichinellosis in Portugal.

Trichinellosis is an emerging or re-emerging foodborne parasitic zoonotic disease caused by nematodes of the genus Trichinella. It represents a global food safety problem and a public health hazard. This case report aims to describe the first case of human trichinellosis in Portugal since the creation of the European Union surveillance system. Infection by Trichinella spp. is a rare cause of hypereosinophilia and hospital admission, but it can cause high morbidity. Clinical detailed history is crucial to obtain a correct diagnosis.

Correction to the article "Implementing an Influenza Vaccine Effectiveness Study in a Hospital Context in Portugal: The EVA Hospital Project", Published on Acta Med Port 2021 Jan;34(1):20-27.

On page 23, Figure 1, where it reads: "Controls 157 2015-2016 season = 47" (area circled in the image bellow) It should read: (see new Figure 1 on pag. 62). On page 25, Table 2, third line of the last column, under "p-value", where it reads: 1 (see Table 2 in page 63) It should read: 1.000 (see new Table 2, page 64) Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/13438.

Na página 23, Figura 1, onde se lê:"Controls 1572015-2016 season = 47"Deverá ler-se: (ver nova Figura 1 na página 62)Na página 25, Tabela 2, terceira linha da última coluna intitulada "p-value", onde se lê: 1 (ver Tabela 2 na pág. 63)Deverá ler-se: 1.000 (ver nova Tabela 2, pág. 64)Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/13438.

Implementing an Influenza Vaccine Effectiveness Study in a Hospital Context in Portugal: The EVA Hospital Project.

INTRODUCTION: The project 'Integrated Monitoring of Vaccines in Europe' aimed to measure seasonal influenza vaccine effectiveness against hospitalised adults, aged 65 years and over, with influenza. We describe the protocol implementation in Portugal. MATERIAL AND METHODS: We implemented a test-negative design, targeting community-dwelling patients aged 65 years old and over hospitalised with severe acute respiratory illness. Patients were reverse transverse-polymerase chain reaction tested for influenza. Cases were those positive for influenza while others were controls. Most variables were collected using hospital medical records. Selection bias was evaluated by comparison with the laboratory influenza test requests database according to demographic characteristics. Crude, season-adjusted influenza vaccine effectiveness was estimated as = 1 - odds ratio, and 95% confidence intervals were obtained by conditional logistical regression, matched with the disease onset month. RESULTS: The recruitment rate was 37.8%. Most participants (n = 368) were female (55.8%) and aged 80 years old and over (55.8%). This was similar to values for potentially eligible severe acute respiratory illness patients (80 years old and over: 56.8%, female: 56.2%). The proportion of missing values was below 2.5% for 20 variables and above 5% (maximum 11.6%) for six variables. Influenza vaccine effectiveness estimates were 62.1% against AH1pdm09 (95% confidence intervals: -28.1 to 88.8), 14.9% against A(H3N2) (95% confidence intervals: -69.6 to 57.3), 43.6% against B/Yam (95% confidence intervals: -66.2 to 80.8). DISCUSSION: Given the non-existence of a coded admission database in either participating hospital the selection of severe acute respiratory illness due to clinical features was the feasible one. These results are only valid for the older adult population residing in the catchment area of the two participating hospitals who were admitted to a public hospital with severe influenza or SARI symptoms. CONCLUSION: Despite the low participation rate, we observed comparable characteristics of participants and eligible severe acute respiratory illness patients. Data quality was high, and influenza vaccine effectiveness results were in accordance with the results of meta-analyses and European season-specific estimates. The final sample size was low, which inhibited obtaining estimates with good precision.

Introdução: O projeto "Integrated Monitoring of Vaccines in Europe" pretende medir a efetividade da vacina antigripal nas hospitalizações por gripe nos adultos com mais de 65 anos. Este estudo pretende descrever a implementação do protocolo em Portugal. Material e Métodos: Implementou-se um estudo com desenho caso-controlo teste negativo. A população-alvo foram indivíduos com idade superior a 65 anos, hospitalizados com doença respiratória aguda grave. Os doentes foram testados para gripe por reverse transverse-polimerase chain reaction. Foram considerados casos aqueles com resultado positivo; os restantes foram controlos. Os dados foram obtidos através de registo clinicos. O potencial viés de seleção foi avaliado por comparação de características demográficas e enfermarias com dados das requisições laboratoriais. A efetividade da vacina, foi estimada em 1 ­ odds ratio por regressão logística condicional, emparelhada para o mês de início da doença. Resultados: A taxa de recrutamento foi de 37,8%. A maioria dos participantes (n = 368) era do sexo feminino (55,8%) e tinha idade superior a 80 anos (55,8%). Padrão similar foi verificado nos doentes elegíveis (idade superior a 80 anos: 56,8%; feminino: 56,2%). Os valores omissos foram inferiores a 2,5% em 20 variáveis e acima de 5% (máximo 11,6%) em seis variáveis. As estimativas da efetividade foram 62,1% contra AH1pdm09 (intervalo de confiança IC 95%: -28,1, 88,8); 14,9% contra A (H3) (intervalo de confiança 95%: -69,6; 57,3) e 43,6% contra B/yamagata (intervalo de confiança 95%: -66,2; 80,8). Discussão: Dada a inexistência de uma codificação em base de dados de admissão em qualquer um dos hospitais participantes, a abordagem de identificação e casos clínicos de doença respiratória aguda grave foi a exequível. Estes resultados são válidos para a população idosa residente na área de abrangência dos dois hospitais participantes que foram internados em um hospital público com gripe grave ou sintomas de doença respiratória aguda grave. Conclusão: Apesar da baixa taxa de participação, observámos características comparáveis entre os participantes e os doentes elegíveis. A qualidade dos dados foi elevada, e os resultados da efetividade concordantes com resultados de meta-análises e estimativas europeias. A reduzida dimensão da amostra impediu a obtenção de estimativas mais precisas.

Community-acquired Escherichia coli meningitis and spondylodiscitis in an adult patient with discoid lupus erythematosus.

Acute bacterial meningitis has a high impact on adult mortality worldwide. Community-acquired Escherichia coli meningitis (CA-ECM) is a rare and poorly described condition and the available knowledge is based on low evidence research, mainly from case reports. We describe a case of CA-ECM in Portugal in an adult patient with discoid lupus erythematosus under immunomodulatory therapy. A 73-year-old woman was admitted to the emergency department with fever and altered mental status over 48 h. Cerebrospinal fluid analysis showed 185 leukocytes/µL, including 85% neutrophils, hypoglycorrhachia (less than 5 mg/dL) and elevated protein of 423 mg/dL with positive culture for Escherichia coli. She was treated with ceftriaxone. Imaging studies also demonstrated spondylodiscitis and arthritis. She responded well to antimicrobial therapy and completed the treatment as an outpatient.

Acute disseminated encephalomyelitis, a rare post-malaria neurological complication: Case report and review of the literature.

There are four neurological complications that can occur after malaria treatment at a time when the patient is aparasitaemic: delayed cerebellar ataxia, acute inflammatory demyelinating polyneuropathy, post-malaria neurological syndrome and acute disseminated encephalomyelitis (ADEM). The authors describe a case of a 54-year-old male who presented with encephalopathy and generalized seizures forty-three days after complete recovery from acute malaria by Plasmodium falciparum. Diagnosis of post-malaria ADEM was made based on the acute onset of the neurological symptoms, characteristic findings in magnetic resonance imaging of the brain and prompt response to steroid therapy. ADEM is an autoimmune demyelinating disease of the central nervous system that usually arises after an infection or vaccination. Its occurrence after malaria infection is relatively rare, and to the best of our knowledge there are only thirteen cases described in the literature.

Epstein-Barr virus hemorrhagic meningoencephalitis: case report and review of the literature.

Neurologic complications related to Epstein-Barr virus (EBV) in immunocompetent adults are rare and most commonly self-limited. However, severe cases have been previously reported in the literature. We describe a case of meningoencephalitis with frontal bilateral hemorrhage in a non-immunocompromised adult following an EBV infection of the central nervous system confirmed by the presence of EBV-DNA in the cerebrospinal fluid. During the patient's hospital stay, there was a favorable clinical and radiologic evolution and the patient was discharged asymptomatic. To our knowledge, this is the fourth case of hemorrhagic meningoencephalitis related to EBV and the first one in an immunocompetent patient with a favorable outcome.

Impact of HIV infection on cardiac deformation.

AIM: The aim of this study was to detect abnormalities in left ventricular myocardial function due to HIV (human immunodeficiency virus) infection without established cardiovascular disease. METHODS: An echocardiogram was performed in 50 asymptomatic HIV-infected patients (age 41 ± 6 years, 64% male) and in 20 healthy individuals. Conventional echocardiography and pulsed tissue Doppler imaging (TDI) were performed according to the guidelines. The strain rate of the basal segments was obtained with color tissue Doppler and used to evaluate systolic strain rate (SRS), early diastolic strain rate (SRE) and late diastolic strain rate (SRA). Longitudinal, radial and circumferential strain were assessed by 2D speckle tracking. RESULTS: The mean duration of HIV infection was 10 ± 5 years, CD4 count was 579 ± 286 cells/mm³, 32% had detectable viral load, and 86% were under treatment. Of the HIV-infected patients, one had grade 1 diastolic dysfunction. The groups were not different except for E wave (HIV 0.72 ± 0.17 m/s vs. control 0.84 ± 0.16 m/s, p=0.01), longitudinal strain (-19.5 ± 1.9% vs. -21 ± 2%, p=0.005), SRS (-1.1 ± 0.28 s⁻¹ vs. -1.3 ± 0.28 s⁻¹, p=0.02) and SRE (1.8 ± 0.4 s⁻¹ vs. 2.2 ± 0.4 s⁻¹, p<0.001), but only SRS (p=0.03, 95% CI 0.036; 0.67) and SRE (p=0.001, 95% CI -0.599; -0.168) had independent value. CONCLUSION: In an HIV-infected population without established cardiovascular disease, myocardial deformation abnormalities can be detected with strain and strain rate, revealing markers of myocardial injury.

HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.

To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.

Enteric mucosa integrity in the presence of a preserved innate interleukin 22 compartment in HIV type 1-treated individuals.

BACKGROUND: Interleukin 22 (IL-22) is emerging as a key cytokine for gut epithelial homeostasis and mucosal repair. Gut disruption is a hallmark of human immunodeficiency virus (HIV) infection. Here, we investigated IL-22 production and gut mucosal integrity in HIV type 1 (HIV-1)-infected individuals receiving long-term antiretroviral therapy (ART). METHODS: Biopsy specimens from 37 individuals who underwent colonoscopy primarily for cancer screening and from 17 HIV-1-infected and 20 healthy age-matched controls were assessed. RESULTS: We found significant depletion of sigmoid IL-22-producing CD4(+) T cells (T-helper type 22 [Th22] cells) even after prolonged ART, contrasting with the apparently normal compartments of regulatory and interleukin 17 (IL-17)-producing CD4(+) T cells, as well as total mucosal CD4(+) T cells. Despite the preferential Th22 cell depletion, IL-22 production by innate lymphoid cells (ILCs) was similar to that observed in HIV-1-seronegative subjects, and transcription of genes encoding molecules relevant for IL-22 production (ie, AHR, IL23, IL23R, IL1B, IL6, and TGFB1) was preserved. Remarkably, levels of transcripts of IL-22-target genes (ie, REG3G, DEFB4A, S100A9, MUC1, and MUC13) were unaltered, suggesting an adequate production of antimicrobial peptides and mucins. In agreement, enteric epithelial architecture was fully preserved. CONCLUSIONS: Despite the reduced Th22 cell subset, innate IL-22-mediated mechanisms, essential for sigmoid mucosa integrity, were fully operational in long-term-treated HIV-1-infected individuals. Our data highlight IL-22 production by ILCs as an important target for therapies aimed at facilitating human mucosal reconstitution.

Direct treatment costs of HIV/AIDS in Portugal / Custos diretos com tratamento do VIH/SIDA em Portugal / Costos originados por tratamiento del VIH/SIDA en Portugal

OBJECTIVE To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. METHODS A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients’ characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. RESULTS The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. CONCLUSIONS The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs. .

OBJETIVO Analizar los costos médicos originados por tratamiento de VIH/SIDA, de acuerdo con la perspectiva del Servicio Nacional de Salud, en Portugal. MÉTODOS Se realizó análisis retrospectivo de registros médicos en muestra de 150 pacientes de cinco centros especializados, en 2008. Se obtuvieron datos de utilización de recursos médicos y de las características de los pacientes, en horizonte temporal de 12 meses. Se aplicó el costo unitario a cada componente de costo, usando fuentes oficiales y datos de contabilidad de los hospitales. RESULTADOS El costo promedio anual del tratamiento fue de 14,277€ por paciente. La parcela de costo más importante fue el relacionado con el tratamiento antiretrovial (9,598€), seguido por los costos de internación (1,323€). Los costos de tratamiento con severidad aumentaron de 11,901€ (> 500 CD4 células/µl) para 23,351€ (CD4 ≤ 50 células/µl). La progresión de los costos se debe mayormente al aumento de los costos de internación, dado que los costos por tratamiento antiretrovial se mantienen constantes a lo largo de las fases. CONCLUSIONES El elevado costo del tratamiento antiretrovial es compensado por el costo relativamente bajo de la internación, a pesar de que éste aumenta con la severidad. La baja progresión de los costos totales revela que estrategias de salud pública alternativas que no alteren la transmisión de la enfermedad tendrán sólo impacto limitado en los gastos, dado que los costos son mayormente influenciados por el tratamiento antiretrovial. .

OBJETIVO Analisar dos custos diretos médicos com VIH/SIDA, de acordo com a perspetiva do Serviço Nacional de Saúde, em Portugal. MÉTODOS Efetuou-se análise retrospectiva de registros médicos em amostra de 150 pacientes de cinco centros especializados em 2008. Foram obtidos dados de utilização de recursos médicos durante 12 meses e das características dos pacientes nesse período. Aplicou-se o custo unitário a cada componente de custo, usando fontes oficiais e dados contabilísticos dos hospitais. RESULTADOS O custo médio anual de tratamento foi de 14.277 euros por paciente. A parcela de custo mais importante foi o custo com o tratamento antirretroviral (9.598 euros), seguido dos custos de internação (1.323 euros). Os custos de tratamento com severidade aumentaram de 11.901 euros (> 500 CD4 células/µl) para 23.351 euros (CD4 ≤ 50 células/µl). A progressão dos custos deve-se principalmente ao aumento dos custos de internação, dado que os custos com tratamento antirretroviral se mantêm constantes ao longo dos estádios. CONCLUSÕES O custo elevado do tratamento antirretroviral é compensado com o custo relativamente baixo da internação, apesar deste aumentar com a severidade. A baixa progressão dos custos totais revela que estratégias de saúde pública alternativas que não alterem a transmissão da doença terão apenas impacto limitado nas despesas, dado que os custos são largamente influenciados pelo do tratamento antirretroviral. .

Direct treatment costs of HIV/AIDS in Portugal.

OBJECTIVE: To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. METHODS: A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients' characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. RESULTS: The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. CONCLUSIONS: The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs.

Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients.

BACKGROUND: The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. METHODS: This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. RESULTS: A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. CONCLUSIONS: Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.

Intralesional expression of mRNA of interferon- gamma , tumor necrosis factor- alpha , interleukin-10, nitric oxide synthase, indoleamine-2,3-dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis.

BACKGROUND: The mechanisms of immunity to Rickettsia conorii that have been elucidated in mouse models have not been evaluated in human tissues. METHODS: In this study, quantitative real-time polymerase chain reaction was used to determine the levels of expression of inflammatory and immune mediators in skin-biopsy samples collected from 23 untreated patients with Mediterranean spotted fever (MSF). RESULTS: In all 23 patients, the levels of intralesional expression of mRNA of tumor necrosis factor (TNF)- alpha , interferon (IFN)- gamma , interleukin (IL)-10, RANTES, and indoleamine-2,3-dioxygenase (IDO), an enzyme involved in limiting rickettsial growth by tryptophan degradation, were higher than those in control subjects; 6 of the 23 patients had high levels of inducible nitric oxide synthase (iNOS), a source of microbicidal nitric oxide. Positive correlations between TNF- alpha , IFN- gamma , iNOS, IDO, and mild/moderate MSF suggest that type 1 polarization plays a protective role. Significantly higher levels of intralesional expression of IL-10 mRNA were inversely correlated with levels of intralesional expression of IFN- gamma mRNA and TNF- alpha mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF. CONCLUSION: Mild/moderate MSF is associated with a strong and balanced intralesional proinflammatory and anti-inflammatory response, with a dominant type 1 immunity, whereas severe MSF is associated with increased expression of chemokine mRNA. Whether these factors are simply correlates of mild and severe MSF or contribute to antirickettsial immunity and pathogenesis remains to be determined.

The presence of eschars, but not greater severity, in Portuguese patients infected with Israeli spotted fever.

In Portugal, Mediterranean spotted fever (MSF) is caused by R. conorii Malish and Israeli spotted fever (ISF) strains. It has been suggested that the ISF strain isolated from patients with MSF causes different clinical manifestations compared to those caused by Malish strain, namely the absence of eschar and greater severity. The aim of this study was to analyze the presence or absence of eschar and of fatality in Portuguese patients infected with either Malish or ISF strain. Of 94 patients with a clinical diagnosis of MSF between 1994 to 2004, 47 were infected with Malish strain and 47 with ISF strain. Eschars were reported in 20 patients (49%) infected with Malish strain, and in 17 (39%) with ISF strain. The presence of eschar is not statistically associated to a greater extent with either R. conorii strain (P=0.346). A total of 22 patients died, 9 infected with Malish strain and 13 infected with ISF strain, and no statistically significant difference was found (P=0.330). This study showed that the concepts of absence of the eschar and greater severity in Israeli spotted fever infection should be revised.