Domestic Triatoma spp. Infections with Trypanosoma cruzi, Household Infestations, and Molecular Identification in Oaxaca, México.

In Latin America, Mexico is the country with the second highest annual estimated number of Chagas disease cases, caused by Trypanosoma cruzi, due to vector-borne transmission. The state of Oaxaca is the location of the first documented human cases of Chagas disease in Mexico and contained the highest T. cruzi seropositive rate (3.5%) from blood donors. Here, entomological surveys, from 2017 to 2019, were conducted to collect triatomines in 124 villages of 60 municipalities. Four principal domestic Triatoma spp. (Hemiptera: Triatominae), Triatoma phyllosoma, T. barberi, T. mazzotti, and T. dimidiata, of Oaxaca, Mexico were identified by morphology and molecular analysis of the barcode region of the cytochrome oxidase 1 (cox1 or COI or CO1) gene. A total of 41 out of 83 T. phyllosoma specimens examined by microscopy were positive for T. cruzi (49%), 49 out of 171 for T. barberi (28%), 31 out of 177 for T. mazzotti (17%), and none out of 10 for T. dimidiata (0%). Overall, the infestation index was 3.1% of households containing at least one triatomine; the crowding index was a mean of two Triatoma spp./household; and the colonization index was 0.38 for households based on presence of nymphs. Geographical distribution of triatomines in Oaxaca at the municipality level and endophilic behavior is also reported. Precise identification, endophilic habits, and infection rates of these triatomines are paramount for vector control programs of the Ministry of Health of Oaxaca and beyond.

In vitro refolding of the structural protein VP1 of parvovirus B19 produces virus-like particles with functional VP1 unique region.

Virus-like particles (VLPs) from Parvovirus B19 (B19V) can be obtained by the self-assembly of the structural proteins VP1 and VP2. It is possible to produce B19V VLPs either from VP2 or a mixture of VP1 and VP2, through its heterologous expression in eukaryotic cells. The difference between VP1 and VP2 protein is a tract of 227 residues located at the N-terminal region of VP1, known as the VP1 unique region (VP1u). This region is critical for B19V infection, including tropism, cell internalization, and lysosomal scape through its phospholipase 2A activity. Herein, we report the in vitro self-assembly of VP1 to form VLPs. These species have phospholipase activity, suggesting that the phospholipase domain is correctly folded. Furthermore, VP1 and VP2 were co-assembled to produce hybrid VLPs which were able to bind and internalize in the non-permissive HepG2 cells, another evidence of the functionality of the in vitro refolded VP1u.

Shorter Time to Discontinuation Due to Treatment Failure in People Living with HIV Switched to Dolutegravir Plus Either Rilpivirine or Lamivudine Compared with Integrase Inhibitor-Based Triple Therapy in a Large Spanish Cohort.

INTRODUCTION: Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). METHODS: All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. RESULTS: Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. CONCLUSION: In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs.

People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects.

eGFR-EPI changes among HIV patients who switch from F/TDF to F/TAF while maintaining the same third agent in the Spanish VACH cohort.

Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited.Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH).Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup.Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m2 (n = 125) was 79.6 (78.0; 81.2) ml/min/1.73m2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m2 at 12 months after switch. In the patient-matched subgroup (n = 175), median annual eGFR-EPI declined -4.24 ml/min/1.73m2 while on F/TDF and increased +0.93 ml/min/1.73m2 after switch to F/TAF (P < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m2, median annual eGFR-EPI increased +4.19 mL/min/1.73m2 after switch (P < 0.0001).Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m2. eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting.

Long-term exposure to particulate matter from air pollution alters airway ß-defensin-3 and -4 and cathelicidin host defense peptides production in a murine model.

Epidemiological studies have associated long-term exposure to environmental air pollution particulate matter (PM) with the development of diverse health problems. They include infectious respiratory diseases related to the deregulation of some innate immune response mechanisms, such as the host defense peptides' expression. Herein, we evaluated in BALB/c mice the effect of long-standing exposure (60 days) to urban-PM from the south of Mexico City, with aerodynamic diameters below 2.5 µm (PM2.5) and 10 µm (PM10) on the lung's gene expression and production of three host defense peptides (HDPs); murine beta-defensin-3, -4 (mBD-3, mBD-4) and cathelin-related antimicrobial peptide (CRAMP). We also evaluated mRNA levels of Il1b and Il10, two cytokines related to the expression of host defense peptides. Exposure to PM2.5 and PM10 differentially induced lung inflammation, being PM2.5, which caused higher inflammation levels, probably associated with a differential deposition on the airways, that facilitate the interaction with alveolar macrophages. Inflammation levels were associated with an early upregulation of the three HDPs assessed and an increment in Il1b mRNA levels. Interestingly, after 28 days of exposure, Il10 mRNA upregulation was observed and was associated with the downregulation of HDPs and Il1b mRNA levels. The upregulation of Il10 mRNA and suppression of HDPs might facilitate microbial colonization and the development of diseases associated with long-term exposure to PM.

Real world effectiveness of standard of care triple therapy versus two-drug combinations for treatment of people living with HIV.

BACKGROUND: Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients. METHODS: A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA<50 copies/mL at baseline, irrespective of the regimen used. The following endpoints were assessed: time to discontinuation for any reason, time to switch due to virologic failure, and time to switch due to toxicity (reasons for discontinuation according to clinician report in the database). Time-to-event analyses were conducted using Kaplan-Meier survival curves and Cox regression models. RESULTS: Overall 7,481 patients were included in the analysis, contributing to 9,243 patient-regimens. Patient characteristics at baseline differed among groups, with the 2DC group being significantly older and having a higher proportion of women, a longer time on ART and a higher number of previous virologic failures. Median (95% Confidence Interval [C.I.]) time to switch was 2.5 years (2.3, 2.7) in 2DC group versus 2.9 years (2.7, 3.0) in TT. Adjusted hazard ratios (95% C.I.) for discontinuation due to any reason, virologic failure and toxicity in the 2DC vs TT group were 1.29 (1.15; 1.44), 2.06 (1.54; 2.77) and 1.18 (0.94; 1.48), respectively. Results were consistent in the two sub-analyses. CONCLUSION: In this analysis, time to discontinuation and probability of remaining free of virologic failure were significantly higher in patients on INSTI-based TT compared to DTG- and/or bPI-containing 2DC, with no differences in toxicity.

Decoration of virus-like particles with an enzymatic activity of biomedical interest.

The natural properties of virus-like particles (VLPs), like their nanometric size, polyvalence, monodispersity and biocompatibility, had called the attention of scientists from different fields. VLPs constitute an excellent platform for the development nanomaterials with a broad spectrum of applications, ranging from physics of soft matter to the development of vaccines and biological nanocarriers. To expand the repertoire of functions of VLPs, they can be decorated with different molecules. In this research, the α-glucosidase Ima1p of Saccharomyces cerevisiae was attached to the surface of in vitro assembled VLPs of parvovirus B19, by using the SpyTag/SpyCatcher system. The resulting particles were structurally characterized displaying a noticeable increase in size compared to the non-decorated VLPs. The study of the biochemical properties of the coupled enzyme indicate that it increased its Vmax by three-fold toward p-nitrophenyl-α-D-glucopyranoside (p-NPG) as substrate. In addition, the linked enzyme displayed a notorious 10 °C shift in its optimal temperature, from 35 °C for the non-attached enzyme, to 45 °C for the enzyme attached to VLPs. The decorated VLPs were also able to act on glycogen; therefore, these particles may be further developed as part of the therapy for treatment of lysosomal storage diseases derived from defects in the human acid α-glucosidase.

Thermal, conformational and rheological properties of κ-carrageenan-sodium stearoyl lactylate gels and solutions.

Polysaccharide-surfactant blends are widely used in foods. However, their possible mutual interactions have not been extensively studied. The purpose of this work was to examine how the anionic surfactant sodium stearoyl lactylate (SSL) affects different properties of κ-carrageenan solutions and gels. Rheometry, differential scanning calorimetry, asymmetrical flow field-flow fractionation coupled with multiangle laser light scattering, among others, were used to determine the flow and viscoelastic behavior, thermal transitions, and conformation changes, respectively. Interference caused by SSL is postulated as the primary factor to explain the variations in the conformation of κ-carrageenan in gels and solutions. However, electrostatic repulsions between κ-carrageenan and SSL can also be involved. These latter interactions are more important for high SSL concentrations (13 mmol dm-3) without addition of KCl, because of the higher net negative charge density of the system. SSL significantly modifies the properties of κ-carrageenan in aqueous media.

Production and characterization of a nanocomposite of highly crystalline nanowhiskers from biologically extracted chitin in enzymatic poly(ε-caprolactone).

A nano-composite from biologically obtained chitin nanofillers homogenously dispersed in a poly(ε-caprolactone) matrix was successfully achieved by an ultrasonication-assisted non-toxic and non-aqueous methodology. For this purpose, biological chitin was obtained from lactic acid fermentation of shrimp wastes and converted into chitin whiskers by acidic hydrolysis in a novel process at low temperature (4°C) that enhanced the distribution and yield. Additionally, the polyester matrix was enzymatically produced in a non-toxic compressed fluid (1,1,1,2-tetrafluoroethane at 25bar and 65°C) medium. The homogeneous distribution of the nanofiller in the matrix was corroborated by confocal and atomic force microscopies. Films of the nanocomposite were physicochemically characterized to assess its adequate properties. Additionally, the qualitative viability of human fibroblasts and osteoblasts cells was studied on the produced nanocomposite films showing good biocompatibility.

The transmission dynamics and diversity of human metapneumovirus in Peru.

BACKGROUND: The transmission dynamics of human metapneumovirus (HMPV) in tropical countries remain unclear. Further understanding of the genetic diversity of the virus could aid in HMPV vaccine design and improve our understanding of respiratory virus transmission dynamics in low- and middle-income countries. MATERIALS & METHODS: We examined the evolution of HMPV in Peru through phylogenetic analysis of 61 full genome HMPV sequences collected in three ecologically diverse regions of Peru (Lima, Piura, and Iquitos) during 2008-2012, comprising the largest data set of HMPV whole genomes sequenced from any tropical country to date. RESULTS: We revealed extensive genetic diversity generated by frequent viral introductions, with little evidence of local persistence. While considerable viral traffic between non-Peruvian countries and Peru was observed, HMPV epidemics in Peruvian locales were more frequently epidemiologically linked with other sites within Peru. We showed that Iquitos experienced greater HMPV traffic than the similar sized city of Piura by both Bayesian and maximum likelihood methods. CONCLUSIONS: There is extensive HMPV genetic diversity even within smaller and relatively less connected cities of Peru and this virus is spatially fluid. Greater diversity of HMPV in Iquitos compared to Piura may relate to higher volumes of human movement, including air traffic to this location.

Construction of protein-functionalized virus-like particles of parvovirus B19.

Decoration of virus-like particles (VLPs) expands the repertory of functions these particles can display. In the last years, VLPs have successfully been used as scaffolds to present different molecules, frequently through the specific reaction of chemical groups on the surface of the particles, or by protein engineering when the presentation of peptides or proteins is the primary goal. VLPs of parvovirus B19 (B19V), have been previously produced in vitro and its stability and ability to assemble into hybrid particles composed of wild-type and chimeric proteins evidenced their potential as research tools. Herein, we report the presentation of functional proteins on the surface of B19V VLPs, through the fusion of the gene coding for the heterologous protein within the gene coding for the structural protein VP2. Two model proteins were used for the construction of chimeras, a lipase from Bacillus pumilus (BplA) and the enhanced green fluorescent protein (EGFP). Both chimeras were folded and successfully assembled in vitro into VLPs. While the BplA chimera exhibited esterase activity, the chimera of EGFP showed no fluorescence. We replaced the EGFP by its fast-folding derivative "super folder GFP" (sfGFP) flanked by larger linkers to increase its movement freedom, which resulted in fluorescent protein able to assemble fluorescent VLPs. These results expand the toolbox for VLP decoration as well as for the construction of new nanobiomaterials.

Improving Disability Care in Countries of the Bolivarian Alliance for the Peoples of Our America.

Persons with disabilities constitute one of the most vulnerable groups in every society; their identification, assessment and care present a major challenge. In 2001-2003, Cuba conducted the first comprehensive national study of persons with disabilities in the Americas. In 2007-2010, the study was replicated in Bolivia, Ecuador, Nicaragua, Saint Vincent and the Grenadines, and Venezuela, at their governments' request. Study results have enabled implementation of strategies with substancial impact on human health in these countries. In response to it, more than a million medical consultations were provided by professionals whose specialties are lacking in the participating countries, including 139,772 clinical genetic consultations. Once each country's needs were identified, Cuba provided technical assistance with equipment supplied by Venezuela. The study led to development of public policies and programs for disability prevention and care of disabled persons in Bolivia, Ecuador, Nicaragua and Venezuela, and the opening of the National Medical Genetics Center and orthotic and prosthetic laboratories in Venezuela, and rehabilitation centers in Bolivia. KEYWORDS Disability, epidemiology, health services research, needs assessment, human resources, workforce, Bolivia, Cuba, Ecuador, Nicaragua, Saint Vincent and the Grenadines, Venezuela.

Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults: rhinovirus among adults and children.

BACKGROUND: human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. OBJECTIVES: to characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. STUDY DESIGN: observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. RESULTS: eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18 years. Fifty-four were HRV-A, 11HRV-B, and 19HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (P trend=0.01). CONCLUSIONS: among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.

Peptide display on a surface loop of human parvovirus B19 VP2: Assembly and characterization of virus-like particles.

Virus-like particles (VLPs) are valuable tools for nanotechnology and nanomedicine. These particles are obtained by the self-assembly, either in vivo or in vitro, of structural proteins of viral capsids. VLPs are excellent scaffolds for surface display of molecules. The N-termini of the structural proteins of human parvovirus B19 (B19V) have been already modified to display peptides or proteins. However, other surface-exposed elements have not been studied as potential locations for peptide display. In this research, we tested the potential of surface loop 62-75 of VP2 protein for the presentation of a 64-residue heterologous peptide. The chimeric protein was able to self-assemble in vitro into VLPs. Improved colloidal stability was observed for these particles, indicating that the peptide is on the surface of the particle. AFM analysis of the chimeric particles shows no obvious difference between the surfaces of particles assembled with VP2 and those assembled with the chimeric VP2. Our results indicate that loop 62-75 is a good candidate for heterologous peptide presentation on the surface of B19V VLPs.

Influenza-like illness sentinel surveillance in one hospital in Medellin, Colombia. 2007-2012.

BACKGROUND: The city of Medellin in Colombia has almost no documentation of the causes of acute respiratory infections (ARIs). As part of an ongoing collaboration, we conducted an epidemiologic surveillance for influenza and other respiratory viruses. It described the influenza strains that were circulating in the region along with their distribution over time, and performing molecular characterization to some of those strains. This will contribute to the knowledge of local and national epidemiology. OBJECTIVES: To analyze viral etiologic agents associated with influenza like illness (ILI) in participants reporting to one General hospital in Medelllin, Colombia. RESULTS: From January 2007 to December 2012, a total of 2039 participants were enrolled. Among them, 1120 (54.9%) were male and 1364 (69%) were under the age of five. Only 124 (6%) were older than the age of 15. From all 2039 participants, 1040 samples were diagnosed by either isolation or RT-PCR. One or more respiratory viruses were found in 737 (36%) participants. Of those, 426 (57.8%) got influenza A or B. Adenoviral and parainfluenza infections represented 19.1% and 14.9% of viral infections, respectively. Influenza A was detected almost throughout the whole year except for the first quarter of 2010, right after the 2009 influenza A pandemic. Influenza B was detected in 2008, 2010, and 2012 with no pattern detected. During 2008 and 2010, both types circulated in about the same proportion. Unusually, in many months of 2012, the proportion of influenza B infections was higher than influenza A (ranging between 30% and 42%). The higher proportion of adenovirus was mainly detected in the last quarter of years 2007 and 2010. Adenoviral cases are more frequent in participants under the age of four. CONCLUSIONS: The phylogenetic analysis of influenza viruses shows that only in the case of influenza A/H1N1, the circulating strains totally coincide with the vaccine strains each year.

Evaluation of the degree of liver fibrosis and genetical characteristics in HIV patients with spontaneous clearance of HCV in Cartagena, Spain.

INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in the region of the Interleukin 28B (IL28B) gene on chromosome 19, coding for the interferon (IFN)-λ3, are involved in hepatitis c virus (HCV), spontaneous clearance. There is little information on the degree of liver fibrosis (LF) in HIV patients, who have had spontaneous clearance of HCV. Our objective in this study is to assess the degree of liver fibrosis in this population, as well as to identify key genetic characteristics associated with spontaneous clearance. MATERIALS AND METHODS: Retrospective descriptive study that evaluated from 1 January 2013 to 30 May 2014, the HIV-HCV coinfected patients in which it has been demonstrated spontaneous clearance of HCV infection. The main variables analyzed were (1) genetics: Haplotype determination of genetic polymorphism SNP rs12979860 in the region of IL 28B gene and (2) grade of LF measured in kilopascals (kPa) by transient elastography (TE). RESULTS: We evaluated 205 patients with HIV and HCV coinfection, of whom, 17 patients (8.3%), presented spontaneous clearance. Fourteen patients (82.4%) had HIV CV<20 copies/mL, while the mean CD4 cell count was 396 (SD: 245) cells/mcL. Nine (53%) patients were analyzed for SNP rs12979860 of IL 28B gene. Nine patients (100%) had the CC haplotypes, and no cases of CT and TT haplotypes were detected (p<0.001). LF was measured by TE in 12 (70.6%) patients. The median of LF (Kpa) was 5.95 (IQR 4.78). In four patients (33.3%) were observed significant LF (F3-F4). In the univariate analysis, no significant differences in the median of LF (Kpa) of HIV patients with spontaneous clearance of HCV were observed with respect to the coinfected HIV-HCV patients with SVR to antiviral therapy (N=34; median 9.6 Kpa; IQR: 10.7; p=0.92) or the coinfected HIV-HCV group who did not receive antiviral therapy (N=124; median 8.5 kPa; IQR: 7.65; p=0.85). CONCLUSIONS: Spontaneous clearance of HCV in our series of patients coinfected with HIV infection represents an uncommon clinical phenomenon. The immune status was preserved and most patients had HIV virological suppression. In all patients in which the IL 28B genetic polymorphism was determined, CC haplotypes were found. The degree of LF (Kpa) in this population was low (<9.5 Kpa) and a low proportion of subjects showed significant LF (F3-F4). No differences in the degree of LF were found in this group compared to coinfected patients receiving HCV treatment with SVR and compared to untreated patients coinfected with HIV-HCV.

Human parainfluenza virus in patients with influenza-like illness from Central and South America during 2006-2010.

BACKGROUND: Human parainfluenza viruses (HPIVs) are common viral causes of community-acquired pneumonia, particularly in children. The four types of HPIV have world-wide distribution; however, limited information exists about the epidemiological profile of HPIV in Latin-America. OBJECTIVE: Provide epidemiologic and phylogenetic information about HPIVs that circulated in Latin America between 2006 and 2010 to better characterize the extent and variability of this respiratory virus in the region. METHODS: Oropharyngeal swabs, demographic data and clinical characteristics were obtained from individuals with influenza-like illness in 10 Latin-American countries between 2006-2010. Specimens were analyzed with culture and molecular methods. RESULTS: A total of 30 561 individuals were enrolled; 991 (3·2%) were HPIV positive. Most infected participants were male (53·7%) and under 5 years of age (68·7%). The HPIV type most frequently isolated was HPIV-3 (403, 40·7%). In 66/2007 (3·3%) hospitalized individuals, HPIV was identified. The most frequent symptoms at enrollment were cough and rhinorrhea. We identified certain patterns for HPIV-1, -2 and -3 in specific cities. Phylogenetic analysis revealed a homogeneous distribution in the region. CONCLUSIONS: In the current scenario, no vaccine or treatment is available for this pathogen. Our results contribute to the scarce epidemiologic and phylogenetic information of HPIV in the region that could support the development of specific management.

Human rhinoviruses and enteroviruses in influenza-like illness in Latin America.

BACKGROUND: Human rhinoviruses (HRVs) belong to the Picornaviridae family with high similarity to human enteroviruses (HEVs). Limited data is available from Latin America regarding the clinical presentation and strains of these viruses in respiratory disease. METHODS: We collected nasopharyngeal swabs at clinics located in eight Latin American countries from 3,375 subjects aged 25 years or younger who presented with influenza-like illness. RESULTS: Our subjects had a median age of 3 years and a 1.2:1.0 male:female ratio. HRV was identified in 16% and HEV was identified in 3%. HRVs accounted for a higher frequency of isolates in those of younger age, in particular children < 1 years old. HRV-C accounted for 38% of all HRVs detected. Phylogenetic analysis revealed a high proportion of recombinant strains between HRV-A/HRV-C and between HEV-A/HEV-B. In addition, both EV-D68 and EV-A71 were identified. CONCLUSIONS: In Latin America as in other regions, HRVs and HEVs account for a substantial proportion of respiratory viruses identified in young people with ILI, a finding that provides additional support for the development of pharmaceuticals and vaccines targeting these pathogens.

Sequential waves of gene expression in patients with clinically defined dengue illnesses reveal subtle disease phases and predict disease severity.

BACKGROUND: Dengue virus (DENV) infection can range in severity from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Changes in host gene expression, temporally through the progression of DENV infection, especially during the early days, remains poorly characterized. Early diagnostic markers for DHF are also lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated host gene expression in a cohort of DENV-infected subjects clinically diagnosed as DF (n = 51) and DHF (n = 13) from Maracay, Venezuela. Blood specimens were collected daily from these subjects from enrollment to early defervescence and at one convalescent time-point. Using convalescent expression levels as baseline, two distinct groups of genes were identified: the "early" group, which included genes associated with innate immunity, type I interferon, cytokine-mediated signaling, chemotaxis, and complement activity peaked at day 0-1 and declined on day 3-4; the second "late" group, comprised of genes associated with cell cycle, emerged from day 4 and peaked at day 5-6. The up-regulation of innate immune response genes coincided with the down-regulation of genes associated with viral replication during day 0-3. Furthermore, DHF patients had lower expression of genes associated with antigen processing and presentation, MHC class II receptor, NK and T cell activities, compared to that of DF patients. These results suggested that the innate and adaptive immunity during the early days of the disease are vital in suppressing DENV replication and in affecting outcome of disease severity. Gene signatures of DHF were identified as early as day 1. CONCLUSIONS/SIGNIFICANCE: Our study reveals a broad and dynamic picture of host responses in DENV infected subjects. Host response to DENV infection can now be understood as two distinct phases with unique transcriptional markers. The DHF signatures identified during day 1-3 may have applications in developing early molecular diagnostics for DHF.