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1.
Emerg Infect Dis ; 29(6): 1250-1253, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37209675

RESUMO

We detected Leishmania RNA virus 1 (LRV1) in 11 isolates of Leishmania (Viannia) panamensis collected during 2014-2019 from patients from different geographic areas in Panama. The distribution suggested a spread of LRV1 in L. (V.) panamensis parasites. We found no association between LRV1 and an increase in clinical pathology.


Assuntos
Leishmania guyanensis , Leishmaniose Cutânea , Leishmaniose Mucocutânea , Leishmaniavirus , Humanos , Leishmania guyanensis/genética , Leishmaniose Mucocutânea/epidemiologia , Leishmaniavirus/genética , Panamá/epidemiologia
2.
Virology ; 579: 101-110, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623351

RESUMO

Zika virus (ZIKV), a mosquito-borne pathogen, is associated with neurological complications in adults and congenital abnormalities in newborns. There are no vaccines or treatments for ZIKV infection. Understanding the specificity of natural antibody responses to ZIKV could help inform vaccine efforts. Here, we used a technology called Deep Sequence-Coupled Biopanning to map the targets of the human antibody responses to ZIKV infection. A bacteriophage virus-like particle (VLP) library displaying overlapping linear peptides derived from the ZIKV polyprotein was generated. The library was panned using IgG from 23 ZIKV-infected patients from Panama and deep sequencing identified common targets of anti-ZIKV antibodies within the ZIKV envelope glycoprotein. These included epitopes within the fusion loop within domain II and four epitopes within domain III. Additionally, we showed that VLPs displaying selected epitopes elicited antibodies that bound to native ZIKV envelope protein but failed to prevent infection in a mouse challenge model.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Humanos , Camundongos , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Epitopos , Proteínas do Envelope Viral/química , Infecção por Zika virus/imunologia
3.
Int J Gynaecol Obstet ; 158(2): 359-367, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34767628

RESUMO

OBJECTIVE: To quantify rates of influenza illness and assess value of influenza vaccination among pregnant women in Panama and El Salvador. METHODS: Pregnant women were enrolled and followed each week in a prospective cohort study to identify acute respiratory illnesses (ARI). Nasopharyngeal swabs obtained from women with febrile ARI were tested by reverse-transcription polymerase chain reaction for influenza and other respiratory viruses. RESULTS: We enrolled 2556 women between October 2014 and April 2017. Sixteen percent developed at least one ARI; 59 had two ARI, and five had three ARI for a total of 463 ARI. Women in El Salvador and Panama contributed 297 person-years (py) and 293 py, respectively, during influenza circulation. Twenty-one (11%) of 196 sampled women tested positive for influenza. Influenza incidence was 5.0/100 py (5.7/100 py in El Salvador and 4.3/100 py in Panama). Only 13% of women in El Salvador and 43% in Panama had been vaccinated against influenza before influenza epidemics (P < 0.0001). CONCLUSIONS: One in six pregnant women developed ARI and more than one in ten ARI were attributable to vaccine-preventable influenza. While women were at risk of influenza, few had been vaccinated before each epidemic. Such findings suggest the utility of evaluations to optimize vaccine timing and coverage.


Assuntos
Vacinas contra Influenza , Influenza Humana , Vírus , Estudos de Coortes , Feminino , Humanos , Incidência , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Gravidez , Gestantes , Estudos Prospectivos
4.
Am J Trop Med Hyg ; 104(4): 1326-1334, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432903

RESUMO

Isolates from 475 cutaneous leishmaniasis (CL) patients from three endemic regions were studied by three typing techniques. The molecular analysis from lesion scrapings based on hsp70 PCR-restriction fragment length polymorphism (RFLP) showed that 78.1% (371/475) restriction patterns corresponded to Leishmania (Viannia) panamensis, 19% (90/475) to Leishmania (Viannia) guyanensis, and 3.0% (14/475) to Leishmania (Viannia) braziliensis. Promastigotes isolated by culture from lesions of 228 patients (48.0%, 228/475) were identified by multi-locus enzyme electrophoresis. Of them, 95.2% (217/228) were typified as L. (V.) panamensis, 1.3% (3/228) as L. (V.) guyanensis, 2.2% (5/228) as L. (V.) braziliensis, and 1.3% (3/228) as hybrids (L. [V.] braziliensis/L. [V.] panamensis). However, a partial sequencing analysis of the hsp70 gene from 77 selected samples showed 16.9% (13/77) typified as L. (V.) panamensis, 68.8% (53/77) as Leishmania (V.) sp., 1, 3.9% (3/77) as L. (V.) guyanensis, 1.3% (1/77) as L. (V.) braziliensis outlier, 2.6% (2/77) as Leishmania (Viannia) naiffi, 2.6% as (2/77) Leishmania (V.) sp., and 2 and 3.9% (3/77) hybrid isolates of L. (V.) braziliensis/L. (V.) guyanensis. These results confirm L. (V.) panamensis as the predominant species and cause of CL lesions in Panama and that L. (V.) guyanensis, L. (V.) braziliensis, and L. (V.) naiffi are circulating to a lower degree. Furthermore, the determination of parasite isolates belonging to atypical clusters and hybrid isolates suggests the circulation of genetic variants with important implications for the epidemiology and clinical follow-up of CL in Panama. No evidence of the existence of parasites of the Leishmania (Leishmania) mexicana complex in Panamanian territory was found in this study.


Assuntos
DNA de Protozoário/análise , Variação Genética , Leishmania/genética , Leishmaniose Cutânea/parasitologia , Impressões Digitais de DNA/métodos , DNA de Protozoário/genética , Leishmania/classificação , Leishmania/isolamento & purificação , Leishmaniose Cutânea/epidemiologia , Leishmaniose Mucocutânea/epidemiologia , Leishmaniose Mucocutânea/parasitologia , Panamá/epidemiologia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
5.
Viruses ; 12(10)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008118

RESUMO

Identifying the specific epitopes targeted by antibodies elicited in response to infectious diseases is important for developing vaccines and diagnostics. However, techniques for broadly exploring the specificity of antibodies in a rapid manner are lacking, limiting our ability to quickly respond to emerging viruses. We previously reported a technology that couples deep sequencing technology with a bacteriophage MS2 virus-like particle (VLP) peptide display platform for identifying pathogen-specific antibody responses. Here, we describe refinements that expand the number of patient samples that can be processed at one time, increasing the utility of this technology for rapidly responding to emerging infectious diseases. We used dengue virus (DENV) as a model system since much is already known about the antibody response. Sera from primary DENV-infected patients (n = 28) were used to pan an MS2 bacteriophage VLP library displaying all possible 10-amino-acid peptides from the DENV polypeptide. Selected VLPs were identified by deep sequencing and further investigated by enzyme-linked immunosorbent assay. We identified previously described immunodominant regions of envelope and nonstructural protein-1, as well as a number of other epitopes. Our refinement of the deep sequence-coupled biopanning technology expands the utility of this approach for rapidly investigating the specificity of antibody responses to infectious diseases.


Assuntos
Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Bioprospecção/métodos , Epitopos/imunologia , Soro/imunologia , Antígenos Virais/química , Dengue/imunologia , Vírus da Dengue/genética , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Humanos , Levivirus/genética , Levivirus/imunologia , Modelos Moleculares , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/química
6.
Int J STD AIDS ; 31(8): 791-799, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32487001

RESUMO

Most of the information on clinical factors related to HIV infection is focused on key populations and young people. Therefore, there is little information on clinical factors related to HIV infection in older persons (>45 years old). In this study, data on CD4 lymphocyte counts were analyzed on adults who are linked to care and have their first CD4 cell count done from different regions of the Republic of Panama from 2012 to 2017. Samples were grouped according to late presentation status, region of origin in the country, year, gender, and age groups. Factors associated with late presentation to care and advanced HIV were assessed on each group by multivariable logistic regression. Late presentation to care was observed in 71.6% of the evaluated subjects, and advanced HIV in 54.5%. Late presentation was associated with males (adjusted odds ratio [AOR] = 1.3, 95% confidence interval [CI]=1.1-1.6, p = 0.03), age greater than 45 years old (AOR = 2.3 CI= 1.8-2.9, p < 0.001), and being from regions where antiretroviral clinics are not well instituted (AOR = 2.1, CI = 1.6-2.7, p < 0.001). Despite an increase in subjects linked to care with a CD4 test performed over the years, late presentation remained constant. Therefore, prevention policies must be reformulated. Promotion of routine HIV testing, accessibility among all population groups, installation of antiretroviral clinics, and implementation of programs as rapid initiation of antiretroviral therapy should be rolled out nationally.


Assuntos
Sorodiagnóstico da AIDS/estatística & dados numéricos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Panamá/epidemiologia , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Fatores de Tempo , Tempo para o Tratamento , Adulto Jovem
7.
Acta Trop ; 204: 105346, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31982434

RESUMO

Scorpions of the Neotropical genus Tityus are responsible for most severe envenomations in the Caribbean, South America, and Lower Central America (LCA). Although Tityus is taxonomically complex, contains high toxin polymorphism, and produces variable clinical manifestations, treatment is limited to antivenoms produced against species with restricted distributions. In this study, we explored the compositional and antigenic diversity of Tityus venoms to provide improved guidelines for the use of available antivenoms at a broader geographic scale. We used immunoblotting, competitive ELISA, and in vivo studies to compare reactivity against commercial antivenoms from Brazil, Venezuela, and Mexico, as well as MALDI-TOF mass spectrometry, cDNA sequencing, and phylogenetic analyses to assess venom sodium channel-active toxin (NaTx) content from medically important Tityus populations inhabiting Brazil, Colombia, Costa Rica, Ecuador, Panama, Trinidad and Tobago, and Venezuela. Additionally, we raised rabbit antibodies against Tityus venoms from LCA to test for cross-reactivity with congeneric species. The results suggest that Tityus spp. possess high venom antigenic diversity, underlying the existence of four toxinological regions in Tropical America, based on venom composition and immunochemical criteria: LCA/Colombia/Amazonia (Region I), Venezuela (Region II), southeast South America (Region III), and a fourth region encompassing species related to toxinologically divergent Tityus cerroazul. Importantly, our molecular and cross-reactivity results highlight the need for new antivenoms against species inhabiting Region I, where scorpions may produce venoms that are not significantly reactive against available antivenoms.


Assuntos
Antivenenos/imunologia , Picadas de Escorpião/epidemiologia , Venenos de Escorpião/imunologia , Escorpiões/classificação , Animais , Colômbia/epidemiologia , Filogenia , Coelhos , Picadas de Escorpião/tratamento farmacológico , Venenos de Escorpião/toxicidade , Especificidade da Espécie
8.
Viruses ; 11(4)2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018496

RESUMO

Mayaro (MAYV) and Una (UNAV) are emerging arboviruses belonging to the Alphavirus genus of the Togaviridae family. These viruses can produce febrile disease with symptoms such as fever, headache, myalgia, skin rash and incapacitating poly-arthralgia. Serological studies indicate that both viruses are circulating in different countries in Latin America. Viruses need the host cell machinery and resources to replicate effectively. One strategy to find new antivirals consists of identifying key cellular pathways or factors that are essential for virus replication. In this study, we analyzed the role of the ubiquitin-proteasome system (UPS) in MAYV and UNAV replication. Vero-E6 or HeLa cells were treated with the proteasome inhibitors MG132 or Lactacystin, and viral progeny production was quantified using a plaque assay method. In addition, the synthesis of viral proteins was analyzed by Western blot and confocal microscopy. Our results indicate that treatment with proteasome inhibitors decreases MAYV and UNAV protein synthesis, and also causes a significant dose-dependent decrease in MAYV and UNAV replication. Proteasome activity seems to be important at the early stages of MAYV replication. These findings suggest that the ubiquitin-proteasome system is a possible pharmacological target to inhibit these neglected alphaviruses.


Assuntos
Alphavirus/efeitos dos fármacos , Antivirais/farmacologia , Complexo de Endopeptidases do Proteassoma/fisiologia , Replicação Viral , Acetilcisteína/análogos & derivados , Acetilcisteína/farmacologia , Alphavirus/fisiologia , Animais , Chlorocebus aethiops , Inibidores de Cisteína Proteinase/farmacologia , Citoplasma/efeitos dos fármacos , Citoplasma/virologia , Células HeLa , Humanos , Leupeptinas/farmacologia , Inibidores de Proteassoma/farmacologia , Células Vero
9.
J Med Virol ; 90(3): 604-608, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28980711

RESUMO

Human metapneumovirus (HMPV) is a common causative agent of severe respiratory tract infections in children under 5 years old, the elderly and immunocompromised patients, being responsible for 5-15% of all viral respiratory infections requiring hospitalization. Though HMPV was included in the surveillance program for respiratory viruses in 2010, its genotype distribution remains unknown. Herein, 45 positive samples to HMPV from children ≤5 years old were characterized by phylogenetic analysis based on N gene sequence. Results showed the co-circulation of four sub-lineages: A2a (8.8%), A2b (55.5%), B1 (15.6%), and B2 (20%), demonstrating the genetic heterogeneity of HMPV circulating in Panamá.


Assuntos
Variação Genética , Metapneumovirus/genética , Infecções por Paramyxoviridae/epidemiologia , Pré-Escolar , Genótipo , Hospitalização , Humanos , Lactente , Nasofaringe/virologia , Panamá/epidemiologia , Infecções por Paramyxoviridae/virologia , Filogenia , RNA Viral/genética , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Análise de Sequência de DNA
10.
AIDS ; 31(14): 1935-1943, 2017 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-28650381

RESUMO

OBJECTIVE: Long-acting rilpivirine is a candidate for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP. METHODS: We analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission. RESULTS: Reverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 × 10) and in all HIV-1 subtypes except A. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 × 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. sub-Saharan Africa, Southeastern Europe) where B18 is more common. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time. CONCLUSIONS: Results illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP.


Assuntos
Antirretrovirais/farmacologia , Farmacorresistência Viral , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Evasão da Resposta Imune , Mutação de Sentido Incorreto , Profilaxia Pré-Exposição , Saúde Global , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , HIV-1/enzimologia , HIV-1/genética , Antígeno HLA-B18/genética , Humanos , Polimorfismo Genético , Rilpivirina/farmacologia
11.
Infect Genet Evol ; 54: 98-107, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28645708

RESUMO

BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0.7%) between 2011 and 2016 were included. Phylogenetic and genetic network analyses were performed to infer putative relationships between HIV sequences. The demographic and geographic associations with clustering were analyzed and viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iterations of random subsets of equal number of sequences per location. RESULTS: A total of 1685/6088 (27.7%) of sequences linked with at least one other sequence, forming 603 putative transmission clusters (range: 2-89 individuals). Clustering individuals were significantly more likely to be younger (median age 29 vs 33years, p<0.01) and men-who-have-sex-with-men (40.4% vs 30.3%, p<0.01). Of the 603 clusters, 30 (5%) included sequences from multiple countries with commonly observed linkages between Mexican and Honduran sequences. Eight of the 603 clusters included >10 individuals, including two comprised exclusively of Guatemalans (52 and 89 individuals). Phylogenetic and migration analyses suggested that the Central and Southern regions of Mexico along with Belize were major sources of HIV throughout the region (p<0.01) with genetic flow southward from Mexico to the other nations of Mesoamerica. We also found evidence of significant viral migration within Mexico. CONCLUSION: International clusters were infrequent, suggesting moderate migration between HIV epidemics of the different Mesoamerican countries. Nevertheless, we observed important sources of transnational HIV spread in the region, including Southern and Central Mexico and Belize.


Assuntos
Infecções por HIV , HIV-1/genética , Adulto , América Central/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Masculino , México/epidemiologia , Epidemiologia Molecular , Adulto Jovem
12.
J Med Virol ; 89(10): 1734-1742, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28464479

RESUMO

In Panama, human respiratory syncytial virus (HRSV) is responsible of 20-40% of acute respiratory infections in children under 5 years old. Currently, little is known about the genetic variability of HRSV in Central America and the Caribbean. Recently, we reported the genetic variability of HRSV-A, however; no studies on HRSV-B in Panama have been described yet. In this study, 24 sequences of Panamanian HRSV-B, from children (<5 years) with acute respiratory infections (ARI), collected from July 2008 to November 2012 were analyzed. All sequences share the characteristic 60-nt duplication of the BA strains. Six Panamanian strains grouped with the BA10 genotype and 12 samples clustered together in a separate monophyletic clade with an aLRT support value of 0.92 and an intra-group p-distance less than 0.07. This fulfills the criteria to consider a new genotype in HRSV, which we named BA14 genotype. Another six strains remain unclassified, but closely related to BA9, BA11, or the new BA14 genotypes, according to their genetic p-distance. Different amino acid substitutions in the Panamanian HRSV-B strains were observed, some previously described and others found only on Panamanian strains. This study contributes to the knowledge of the genetic variability and evolution of HRSV in Central America.


Assuntos
Variação Genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Pré-Escolar , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Panamá/epidemiologia , Filogenia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/virologia , Análise de Sequência de DNA
13.
PLoS One ; 12(2): e0171511, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28152075

RESUMO

Identifying the targets of antibody responses during infection is important for designing vaccines, developing diagnostic and prognostic tools, and understanding pathogenesis. We developed a novel deep sequence-coupled biopanning approach capable of identifying the protein epitopes of antibodies present in human polyclonal serum. Here, we report the adaptation of this approach for the identification of pathogen-specific epitopes recognized by antibodies elicited during acute infection. As a proof-of-principle, we applied this approach to assessing antibodies to Dengue virus (DENV). Using a panel of sera from patients with acute secondary DENV infection, we panned a DENV antigen fragment library displayed on the surface of bacteriophage MS2 virus-like particles and characterized the population of affinity-selected peptide epitopes by deep sequence analysis. Although there was considerable variation in the responses of individuals, we found several epitopes within the Envelope glycoprotein and Non-Structural Protein 1 that were commonly enriched. This report establishes a novel approach for characterizing pathogen-specific antibody responses in human sera, and has future utility in identifying novel diagnostic and vaccine targets.


Assuntos
Formação de Anticorpos/fisiologia , Epitopos/imunologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Infecções/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Dengue/imunologia , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/genética , Humanos , Imunoglobulina G/imunologia , Levivirus/imunologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Biblioteca de Peptídeos
15.
PLoS One ; 11(4): e0154317, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27119150

RESUMO

The use of antiretroviral therapy in HIV infected subjects prevents AIDS-related illness and delayed occurrence of death. In Panama, rollout of ART started in 1999 and national coverage has reached 62.8% since then. The objective of this study was to determine the level and patterns of acquired drug resistance mutations of clinical relevance (ADR-CRM) and surveillance drug resistance mutations (SDRMs) from 717 HIV-1 pol gene sequences obtained from 467 ARV drug-experienced and 250 ARV drug-naïve HIV-1 subtypes B infected subjects during 2007-2013, respectively. The overall prevalence of SDRM and of ADR-CRM during the study period was 9.2% and 87.6%, respectively. The majority of subjects with ADR-CRM had a pattern of mutations that confer resistance to at least two classes of ARV inhibitors. The non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K103N and P225H were more prevalent in both ARV drug-naïve and ARV drug-experienced subjects. The nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V was more frequent in ARV drug-experienced individuals, while T215YFrev and M41L were more frequent in ARV drug-naïve subjects. Prevalence of mutations associated to protease inhibitors (PI) was lower than 4.1% in both types of subjects. Therefore, there is a high level of resistance (>73%) to Efavirenz/Nevirapine, Lamivudine and Azidothymidine in ARV drug-experienced subjects, and an intermediate to high level of resistance (5-10%) to Efavirenz/Nevirapine in ARV drug-naïve subjects. During the study period, we observed an increasing trend in the prevalence of ADR-CRM in subjects under first-line schemes, but not significant changes in the prevalence of SDRM. These results reinforce the paramount importance of a national surveillance system of ADR-CRM and SDRM for national management policies of subjects living with HIV.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Mutação , Adulto , Idoso , Alcinos , Benzoxazinas/farmacologia , Ciclopropanos , Feminino , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Nevirapina/farmacologia , Panamá , Prevalência , Estudos Retrospectivos , Adulto Jovem
16.
J Med Virol ; 88(3): 389-94, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26252655

RESUMO

The human bocavirus (HBoV) was added as a new member of the Parvoviridae family in 2005 upon its discovery in nasopharyngeal aspirates from children with respiratory infection. Recently, there has been increasing evidence of worldwide circulation of HBoV; however, in Latin America few studies have been conducted. In order to detect the circulation of HBoV in Panama, based on the National Flu Surveillance System, we developed this retrospective, cross-sectional study, from January 2011 to January 2012. Children younger than 6 years old who presented with respiratory disease were enrolled in this study. Nasopharyngeal swabs were taken in sentinel surveillance sites. Samples were tested to detect mRNA from HBoV, as well as viral RNA and DNA from others respiratory viruses. A total of 1078 patients were enrolled in this study. Overall, 44 (4.1%) of the patients presented HBoV. The most common symptoms were cough (84.6%), fever (82.1%), rhinorrhea (74.4%), and sore throat (38.5%). Less than half (45.5%) of HBoV infected patients presented with monoinfection while 54.5% of cases presented with coinfection with others respiratory viruses. Both, outpatients and inpatients were included in this study. Outpatients corresponded to 52.3% of the cases and 47.7% were inpatients. Coinfection was observed in the 50% of the inpatient cases. Phylogenetic analyses indicated that the circulating strains belonged to different clades of HBoV genotype 1. Taken together, our results support the pathogenic nature of this viral agent, especially in younger children.


Assuntos
Bocavirus Humano/genética , Bocavirus Humano/isolamento & purificação , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/virologia , Infecções Respiratórias/virologia , Criança , Pré-Escolar , Coinfecção/virologia , Tosse/etiologia , Tosse/virologia , Estudos Transversais , Feminino , Febre/etiologia , Febre/virologia , Genótipo , Bocavirus Humano/classificação , Bocavirus Humano/patogenicidade , Humanos , Lactente , Masculino , Nasofaringe/virologia , Panamá/epidemiologia , Infecções por Parvoviridae/epidemiologia , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/análise , Estudos Retrospectivos , Análise de Sequência de DNA , Carga Viral
17.
PLoS One ; 10(7): e0134850, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26230260

RESUMO

The Hepatitis B Virus (HBV) can cause acute or chronic infection it is also associated with the development of liver cancer, thousands of new infections occur on a yearly basis, and many of these cases are located in certain areas of the Caribbean and Latin America. In these areas, the HBV prevalence is still high which makes this virus a serious public health concern to the entire region. Studies performed in Panama suggest a complex pattern in the distribution of HBV among the country's different risk groups. We use phylogenetic analysis in order to determine which HBV genotypes were circulating in these specific groups; for this we used a fragment of the PreS2/2 region of the HBV genome. Subsequently whole HBV genome sequences were used for Bayesian analysis of phylodynamics and phylogeography. Two main genotypes were found: genotype A (54.5%) and genotype F (45.5%). There was a difference in the distribution of genotypes according to risk groups: 72.9% of high risk groups were associated to genotype A, and 55.0% of samples of genotype F were associated to the low risk group (p<0.002). The Bayesian analysis of phylogeny-traits association revealed a statistically significant geographical association (p<0.0001) with both genotypes and different regions of the country. The Bayesian time of most recent common ancestor analysis (tMRCA) revealed a recent tMRCA for genotype A2 circulating in Panama (1997, 95% HPD: 1986-2005), when it is compared with Panamanian genotype F1c sequences (1930, 95% HPD: 1810 - 2005). These results suggest a possible change in the distribution of HBV genotypes in Panama and Latin America as a whole. They also serve to encourage the implementation of vaccination programs in high-risk groups, in order to prevent an increase in the number of new HBV cases in Latin America and worldwide.


Assuntos
Vírus da Hepatite B/classificação , Filogenia , Genótipo , Vírus da Hepatite B/genética , Panamá
18.
J Virol ; 89(15): 7776-85, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25995258

RESUMO

UNLABELLED: Worldwide G-glycoprotein phylogeny of human respiratory syncytial virus (hRSV) group A sequences revealed diversification in major clades and genotypes over more than 50 years of recorded history. Multiple genotypes cocirculated during prolonged periods of time, but recent dominance of the GA2 genotype was noticed in several studies, and it is highlighted here with sequences from viruses circulating recently in Spain and Panama. Reactivity of group A viruses with monoclonal antibodies (MAbs) that recognize strain-variable epitopes of the G glycoprotein failed to correlate genotype diversification with antibody reactivity. Additionally, no clear correlation was found between changes in strain-variable epitopes and predicted sites of positive selection, despite both traits being associated with the C-terminal third of the G glycoprotein. Hence, our data do not lend support to the proposed antibody-driven selection of variants as a major determinant of hRSV evolution. Other alternative mechanisms are considered to account for the high degree of hRSV G-protein variability. IMPORTANCE: An unusual characteristic of the G glycoprotein of human respiratory syncytial virus (hRSV) is the accumulation of nonsynonymous (N) changes at higher rates than synonymous (S) changes, reaching dN/dS values at certain sites predictive of positive selection. Since these sites cluster preferentially in the C-terminal third of the G protein, like certain epitopes recognized by murine antibodies, it was proposed that immune (antibody) selection might be driving the apparent positive selection, analogous to the antigenic drift observed in the influenza virus hemagglutinin (HA). However, careful antigenic and genetic comparison of the G glycoprotein does not provide evidence of antigenic drift in the G molecule, in agreement with recently published data which did not indicate antigenic drift in the G protein with human sera. Alternative explanations to the immune-driven selection hypothesis are offered to account for the high level of G-protein genetic diversity highlighted in this study.


Assuntos
Anticorpos Monoclonais/imunologia , Epitopos/genética , Evolução Molecular , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , Anticorpos Antivirais/imunologia , Variação Antigênica , Sequência Conservada , Epitopos/química , Epitopos/imunologia , Variação Genética , Humanos , Dados de Sequência Molecular , Filogenia , Vírus Sincicial Respiratório Humano/química , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/imunologia , Alinhamento de Sequência , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia
19.
PLoS One ; 9(8): e103545, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25093674

RESUMO

Hepatitis B Virus (HBV) is an infectious agent that causes more than half of the cases of liver disease and cancer in the world. Globally there are around 250 million people chronically infected with this virus. Despite 16% of the cases of liver disease in Central America are caused by HBV, the information regarding its genetic diversity, genotypes and circulation is scarce. The purpose of this study was to evaluate the genetic variability of the HBV genotypes from HBV-DNA positive samples obtained from screening blood donors at the Social Security System of Panama and to estimate its possible origin. From 59,696 blood donors tested for HBV infection during 2010-2012, there were 74 HBV-DNA positive subjects. Analysis of the partial PreS2-S region of 27 sequences shows that 21% of the infections were caused by genotype A, 3% by genotype D and 76% by genotype F. In addition, we were able to confirm circulation of six sub-genotypes A1, A2, A3, D4, F3, F1 and a proposed new sub-genotype denominated F5pan. We found a confinement of sub-genotypes F1 and F5pan to the western area of Panama. The tMRCA analysis suggests a simultaneous circulation of previously described sub-genotypes rather than recent introductions of the Panamanian sub-genotypes in the country. Moreover, these results highlight the need of more intensive research of the HBV strains circulating in the region at the molecular level. In conclusion, Panama has a high HBV genotype diversity that includes a new proposed sub-genotype, an elevated number of PreCore-Core mutations, and confinement of these variants in a specific geographical location.


Assuntos
Doadores de Sangue , Variação Genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Doadores de Sangue/estatística & dados numéricos , Análise Mutacional de DNA , DNA Viral/genética , Genótipo , Hepatite B/sangue , Hepatite B/epidemiologia , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Dados de Sequência Molecular , Panamá/epidemiologia , Filogenia , Análise de Sequência de DNA , Estudos Soroepidemiológicos
20.
J Urban Health ; 91(4): 793-808, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24927712

RESUMO

Respondent-driven sampling (RDS) was used to conduct a biobehavioral survey among men who have sex with men (MSM) in three cities in the Republic of Panama. We estimated the prevalence of HIV, syphilis, and other sexually transmitted infections (STIs), sociodemographic characteristics, and sexual risk behaviors. Among 603 MSM recruited, RDS-adjusted seroprevalences (95 % confidence intervals) were: HIV-David 6.6 % (2.2-11.4 %), Panama 29.4 % (19.7-39.7 %), and Colon 32.6 % (18.0-47.8 %); active syphilis-David 16.0 % (8.9-24.2 %), Panama 24.7 % (16.7-32.9 %), Colon 31.6 % (14.8-47.5 %); resolved HBV infection-David 10.0 % (4.8-16.8 %), Panama 29.4 % (20.0-38.3 %), and Colon 40.6 % (21.9-54.4 %); herpes simplex virus type 2-David 38.4 % (27.9-48.9 %), Panama 62.6 % (52.8-71.0 %), and Colon 72.9 % (57.4-85.8 %). At least a third of MSM in each city self-identified as heterosexual or bisexual. HIV prevalence is concentrated among MSM. Preventive interventions should focus on increasing HIV and syphilis testing, and increasing promotion of condom awareness and use.


Assuntos
Infecções por HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/epidemiologia , População Urbana/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Panamá/epidemiologia , Prevalência , Fatores de Risco , Assunção de Riscos , Fatores Socioeconômicos , Adulto Jovem
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