Identification of Chagas disease biomarkers using untargeted metabolomics.

Untargeted metabolomic analysis is a powerful tool used for the discovery of novel biomarkers. Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease that affects 6-7 million people with approximately 30% developing cardiac manifestations. The most significant clinical challenge lies in its long latency period after acute infection, and the lack of surrogate markers to predict disease progression or cure. In this cross-sectional study, we analyzed sera from 120 individuals divided into four groups: 31 indeterminate CD, 41 chronic chagasic cardiomyopathy (CCC), 18 Latin Americans with other cardiomyopathies and 30 healthy volunteers. Using a high-throughput panel of 986 metabolites, we identified three distinct profiles among individuals with cardiomyopathy, indeterminate CD and healthy volunteers. After a more stringent analysis, we identified some potential biomarkers. Among peptides, phenylacetylglutamine and fibrinopeptide B (1-13) exhibited an increasing trend from controls to ICD and CCC. Conversely, reduced levels of bilirubin and biliverdin alongside elevated urobilin correlated with disease progression. Finally, elevated levels of cystathionine, phenol glucuronide and vanillactate among amino acids distinguished CCC individuals from ICD and controls. Our novel exploratory study using metabolomics identified potential biomarker candidates, either alone or in combination that if confirmed, can be translated into clinical practice.

Quantitative Proteomic Analysis of Macrophages Infected with Trypanosoma cruzi Reveals Different Responses Dependent on the SLAMF1 Receptor and the Parasite Strain.

Chagas disease is caused by the intracellular protozoan parasite Trypanosoma cruzi. This disease affects mainly rural areas in Central and South America, where the insect vector is endemic. However, this disease has become a world health problem since migration has spread it to other continents. It is a complex disease with many reservoirs and vectors and high genetic variability. One of the host proteins involved in the pathogenesis is SLAMF1. This immune receptor acts during the infection of macrophages controlling parasite replication and thus affecting survival in mice but in a parasite strain-dependent manner. Therefore, we studied the role of SLAMF1 by quantitative proteomics in a macrophage in vitro infection and the different responses between Y and VFRA strains of Trypanosoma cruzi. We detected different significant up- or downregulated proteins involved in immune regulation processes, which are SLAMF1 and/or strain-dependent. Furthermore, independently of SLAMF1, this parasite induces different responses in macrophages to counteract the infection and kill the parasite, such as type I and II IFN responses, NLRP3 inflammasome activation, IL-18 production, TLR7 and TLR9 activation specifically with the Y strain, and IL-11 signaling specifically with the VFRA strain. These results have opened new research fields to elucidate the concrete role of SLAMF1 and discover new potential therapeutic approaches for Chagas disease.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

Incidence of Anal Cancer and Related Risk Factors in HIV-Infected Patients Enrolled in the National Prospective Spanish Cohort CoRIS.

BACKGROUND: People living with HIV have an increased risk of anal cancer. OBJECTIVE: To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. DESIGN: Prospective multicenter cohort study. SETTINGS: Multicenter study including patients from the Spanish HIV Research Network. PATIENTS: We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. MAIN OUTCOMES MEASURES: The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. RESULTS: Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). LIMITATIONS: Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. CONCLUSIONS: Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. INCIDENCIA DEL CNCER DE ANO Y LOS FACTORES DE RIESGO RELACIONADOS CON PACIENTES INFECTADOS POR VIH INCLUIDOS EN LA COHORTE PROSPECTIVA NACIONAL ESPAOLA CORIS: ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).

Expert Consensus: Main Risk Factors for Poor Prognosis in COVID-19 and the Implications for Targeted Measures against SARS-CoV-2.

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm3; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir <200/mm3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

Effects of frailty, geriatric syndromes, and comorbidity on mortality and quality of life in older adults with HIV.

BACKGROUND: To understand the effects of frailty, geriatric syndromes, and comorbidity on quality of life and mortality in older adults with HIV (OAWH). METHODS: Cross-sectional study of the FUNCFRAIL multicenter cohort. The setting was outpatient HIV-Clinic. OAWH, 50 year or over were included. We recorded sociodemographic data, HIV infection-related data, comorbidity, frailty, geriatric syndromes (depression, cognitive impairment, falls and malnutrition), quality of life (QOL) and the estimated risk of all-cause 5-year mortality by VACS Index. Association of frailty with geriatric syndromes and comorbidity was evaluated using the Cochran-Mantel-Haenszel test. RESULTS: Seven hundred ninety six patients were included. 24.7% were women, mean age was 58.2 (6.3). 14.7% were 65 or over. 517 (65%) patients had ≥3 comorbidities, ≥ 1 geriatric syndrome and/or frailty. There were significant differences in the estimated risk of mortality [(frailty 10.8%) vs. (≥ 3 comorbidities 8.2%) vs. (≥ 1 geriatric syndrome 8.2%) vs. (nothing 6.2%); p = 0.01] and in the prevalence of fair or poor QOL [(frailty 71.7%) vs. (≥ 3 comorbidities 52%) vs. (≥ 1 geriatric syndrome 58.4%) vs. (nothing 51%); p = 0.01]. Cognitive impairment was significantly associated to mortality (8.7% vs. 6.2%; p = 0.02) and depression to poor QOL [76.5% vs. 50%; p = 0.01]. CONCLUSIONS: Frailty, geriatric syndromes, and comorbidity had negative effects on mortality and QOL, but frailty had the greatest negative effect out of the three factors. Our results should be a wake-up call to standardize the screening for frailty and geriatric syndromes in OAWH in the clinical practice. TRIAL REGISTRATION: NCT03558438.

Different profiles among older adults with HIV according to their chronological age and the year of HIV diagnosis: The FUNCFRAIL cohort study (GeSIDA 9817).

BACKGROUND: People in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group. OBJECTIVE: To evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis. METHODS: Cross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL). RESULTS: We evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB <10) but they were more than twice as prevalent in the 65 or over patients compared to the other chronological age groups. CONCLUSIONS: A LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.

Exploiting the Microbiota for the Diagnosis of Anal Precancerous Lesions in Men Who Have Sex With Men.

BACKGROUND: While the microbiota has been associated with human papillomavirus malignant transformation, it is unclear whether anal bacteria could improve the low specificity of anal cytology for the screening of high-grade intraepithelial squamous neoplasia (HSIL). METHODS: We recruited men who have sex with men undergoing anal cytology and high-resolution anoscopy. We assessed the microbiota composition from fecal samples and cytobrush anal samples using 16S ribosomal DNA sequencing in participants with or without biopsy-proven HSIL (bHSIL). We selected bacterial biomarkers based on their linear discriminant analysis. We assessed their predictive performance using logistic regression and bootstrap resampling. RESULTS: We included 128 individuals, 47 (36.7%) with bHSIL and 99 (77.3%) with human immunodeficiency virus. We detected 40 potential predictors of bHSIL. Ruminococcaceae NK4A214 group, Alloprevotella genus, Prevotella melanonigenica, and Ruminococcaceae UCG-014 were the most predictive of bHSIL. From 35 false-positive cytologic results, the combination of these 4 biomarkers with the anal cytology reclassified to true-negative 33 individuals (94%) and showed good diagnostic performance (area under the receiver operating characteristic curve, 0.805; 95% confidence interval, .728-.882). CONCLUSIONS: We found anal-associated bacteria indicative of a higher risk of precancerous anal lesions, which combination was highly specific. The microbiota could be developed as a complementary diagnostic tool to overcome the limitations of the current screening strategy for anal cancer.

Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity.

The receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal Trypanosoma cruzi Y strain. To elucidate whether genetic diversity of the parasite was related with disease susceptibility, we further analyzed the role of SLAMF1 using 6 different Trypanosoma cruzi strains including Y. The interaction of SLAMF1 receptor with T. cruzi was evidenced by fluorescence microscopy, flow cytometry and quantitative PCR. All the strains, except VFRA, showed a decrease in parasite load in infected macrophages in Slamf1-/- compared to BALB/c. In macrophages gene expression NADPH oxidase (NOX2), and reactive oxygen species (ROS) production increased in Slamf1-/- compared to BALB/c in 5 out of 6 strains. However, Slamf1-/-macrophages infected with VFRA strain exhibited a divergent behavior, with higher parasite load, lower NOX2 expression and ROS production compared to BALB/c. Parasitological and immunological studies in vivo with Y strain showed that in the absence of SLAMF1 the immune response protected mice from the otherwise lethal Y infection favoring a proinflammatory response likely involving CD4, CD8, dendritic cells and classically activated macrophages. In the case of VFRA, no major changes were observed in the absence of SLAMF1. Thus, the results suggest that the T. cruzi affects SLAMF1-dependent ROS production, controlling parasite replication in macrophages and affecting survival in mice in a strain-dependent manner. Further studies will focus in the identification of parasite molecules involved in SLAMF1 interaction to explain the immunopathogenesis of the disease.

Histiocytic hyperplasia with hemophagocytosis and acute alveolar damage in COVID-19 infection.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients.

Plasma levels of adenosine deaminase (ADA), an enzyme that deaminates adenosine to inosine, are increased during inflammation. An increase in ADA activity occurs with lower human immunodeficiency virus (HIV) viral load and higher CD4+ T cell counts. We aimed to investigate the role of plasma ADA as a biomarker of inflammation in treatment-naïve HIV patients who received tenofovir or another nucleoside analog for comparison. Ninety-two treatment-naïve patients were included in the study and grouped by treatment, i.e., tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or Triumeq. ADA activity was measured in plasma and cytokines were analyzed by MILLIPLEX® MAP-Luminex® Technology. Plasma concentration of monocytes and neutrophils was measured at 0, 3, and 12 months post-treatment. Treatment-naïve HIV patients had increased ADA concentrations (over 15 U/L) that decreased after treatment with TAF and Triumeq, though this did not occur in TDF-treated patients. However, all groups exhibited a pro-inflammatory systemic profile at 12 months of treatment. Plasma GM-CSF levels decreased after 12 months of treatment in the TDF group, with a concomitant decrease in blood monocyte count, and a negative correlation with ADA values was found. In conclusion, ADA levels may be modulated by antiretroviral therapy in HIV patients, possibly affecting inflammatory status.

Drug-related and psychopathological symptoms in HIV-positive men who have sex with men who inject drugs during sex (slamsex): Data from the U-SEX GESIDA 9416 Study.

OBJECTIVES: Sexualized intravenous drug use, also known as slamsex, seems to be increasing among HIV-positive men who have sex with men (MSM). Physical and psychopathological symptoms have previously been reported in this population, although research on the subject of slamsex is scarce. The objectives of our study were to describe the psychopathological background of a sample of HIV-positive MSM who engaged in slamsex during the previous year and to compare physical, psychopathological, and drug-related symptoms between these participants and those who engaged in non-injecting sexualized drug use. DESIGN AND METHODS: Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional online survey on sexual behavior and recreational drug use. When participants met the inclusion criteria, physicians offered them the opportunity to participate and gave them a card with a unique code and a link to access the online survey. The present analysis is based on HIV-positive MSM who had engaged in slamsex and non-injecting sexualized drug use. RESULTS: The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) had engaged in chemsex, and of these, 34 (15.7%) had engaged in slamsex. Participants who engaged in slamsex were more likely to have current psychopathology (depression, anxiety, and drug-related disorders) than participants who engaged in non-injecting sexualized drug use. In addition, participants who engaged in slamsex more frequently reported high-risk sexual behaviors and polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with participants who did not inject drugs, participants who engaged in slamsex experienced more severe drug-related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms during or after slamsex (eg, paranoid thoughts and suicidal behaviors). CONCLUSION: Slamsex is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.

CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control.

A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = -0.46, p = 0.043) and of CCR6 (rho = -0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.

Diagnosis of cutaneous anthrax in resource-poor settings in West Arsi Province, Ethiopia.

INTRODUCTION: Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low- and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. MATERIAL AND METHODS: The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 - 56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010-2013. RESULTS: In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. CONCLUSIONS: Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

Both Hepatitis C Virus-Specific T Cell Responses and IL28B rs12979860 Single-Nucleotide Polymorphism Genotype Influence Antihepatitis C Virus Treatment Outcome in Patients with Chronic Hepatitis C.

Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy. The interdependence and roles of T cell-mediated immune responses and IL28B rs12979860 single-nucleotide polymorphism genotype as predictors of virological response to anti-HCV treatment in patients with chronic hepatitis C were evaluated using nonparametric tests. Factors associated with rapid virological response (RVR) in univariate analysis were presence of CD4 T cell response against NS3 HCV protein, low baseline HCV-RNA, and IL28B CC genotype. Factors associated with sustained virological response (SVR) in univariate analysis were IL28B CC genotype, low baseline HCV-RNA, and presence of CD4 response against NS2. In the multivariate analysis, low baseline HCV-RNA and NS3-specific CD4 response showed a clear trend toward association with RVR (P = 0.09 and P = 0.07, respectively). Regarding SVR, IL28B CC genotype was the strongest predictor (P = 0.02), with presence of NS2-specific CD4 response showing a clear trend (P = 0.09). HCV-specific T cell response influences the outcome of pegIFNα/RBV therapy regardless of IL28B genotype. HCV-specific T cell responses (adaptive immunity) seem to influence viral clearance both in the short and long term during therapy (RVR and SVR), whereas the influence of the IL28B genotype (innate immunity) may be more relevant to the long-lasting therapeutic effect (SVR).

Successful treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement.

Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris is an uncommon infection for which there is no optimal therapy. We describe a young, female patient who presented with extensive cutaneous and neurological involvement and who recovered after receiving prolonged treatment with miltefosine, fluconazole, and albendazole.