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Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease in older adults. Understanding the disease burden is crucial for guiding vaccination policy and raising disease awareness. We estimated the burden of RSV hospitalizations and deaths in adults in five middle-income countries: Argentina, Brazil, Chile, Mexico, and Malaysia. Hospital discharge and death statistics due to any respiratory disease (ICD-10 codes: J00-99) from 2010 to 2022 were obtained. The RSV attributable burden on hospitalizations and deaths by age group was determined for 2019 using previously published estimates. Latin American countries showed distinct annual peaks in respiratory-related hospitalizations and deaths during winter months that were absent in Malaysia. Among ≥20-year-olds in 2019, there were 14,604 RSV-attributable hospitalizations nationally in Argentina, 44,323 in Brazil, 4529 in Chile, 7416 in Malaysia, and 8651 in Mexico, and 60-74% in ≥65-year-olds. There were also 3518 RSV-attributable deaths in Argentina, 9115 in Brazil, 801 in Chile, 704 in Malaysia, and 3806 in Mexico 79-88% in ≥65-year-olds. Incidences of RSV-attributable hospitalizations in ≥75-year-olds ranged between 256.3 and 294.3 per 100,000 population, and deaths between 33.6 and 112.9 per 100,000 population. RSV is associated with a substantial disease burden beyond pediatric age groups, and preventive vaccines could have a major impact on this burden, especially in older adults.
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Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition, mainly affecting infants. In 2017, Argentina introduced a vaccination program against serogroups A, C, W and Y (MenACWY) for infants aged 3, 5 and 15 months and adolescents aged 11 years. The objective of this study was to review the burden of IMD in Argentina in 2010-2019. Data were obtained from national surveillance databases, and the study estimated IMD incidence, mortality, case-fatality rates, and serogroup distributions across age groups. A total of 1,972 IMD cases were reported in the study period, with the highest incidence in infants aged < 1 year. Incidence peaked in 2013 and subsequently declined. Mortality rates were 18 times higher in infants than in other age groups, reflecting the high impact of IMD in this age group. The case-fatality rate was 8.5% on average and increased with age. The proportion of notified cases with serogroup identification increased over the period, reaching 91% in 2019. The most common serogroups over the study period were serogroup B (48%) and serogroup W (42%), with an increase in B relative to W since 2015. In infants aged < 1 year, the proportion of serogroup B increased in recent years, reaching around 70% of characterized cases in 2018-2019. These results show the dynamism of IMD and indicate the importance of vaccination at an early age and offering protection against predominant serogroups. These data are valuable to support evidence-based decision-making in healthcare.
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Infecciones Meningocócicas , Adolescente , Lactante , Humanos , Argentina/epidemiología , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Bases de Datos Factuales , Instituciones de Salud , Costo de EnfermedadRESUMEN
BACKGROUND: Detailed information is needed on the dynamic pattern of antimicrobial resistance (AMR) in Neisseria gonorrhoeae in Latin America and the Caribbean (LAC). OBJECTIVES: To conduct a systematic review of AMR in N. gonorrhoeae in LAC. METHODS: Electronic searches without language restrictions were conducted in PubMed, Embase, Cochrane Library, EconLIT, Cumulative Index of Nursing and Allied Health Literature, Centre for Reviews and Dissemination, and Latin American and Caribbean Literature in Health Sciences. Studies were eligible if published between 1 January 2011 and 13 February 2021, conducted in any LAC country (regardless of age, sex and population) and measured frequency and/or patterns of AMR to any antimicrobial in N. gonorrhoeae. The WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO-GASP) for LAC countries and Latin American AMR SurveillanceNetwork databases were searched. AMR study quality was evaluated according to WHO recommendations. RESULTS: AMR data for 38,â417 isolates collected in 1990-2018 were included from 31 publications, reporting data from Argentina, Brazil, Colombia, Peru, Uruguay, Venezuela and WHO-GASP. Resistance to extended-spectrum cephalosporins was infrequent (0.09%-8.5%). Resistance to azithromycin was up to 32% in the published studies and up to 61% in WHO-GASP. Resistance to penicillin, tetracycline and ciprofloxacin was high (17.6%-98%, 20.7%-90% and 5.9%-89%, respectively). Resistance to gentamicin was not reported, and resistance to spectinomycin was reported in one study. CONCLUSIONS: This review provides data on resistance to azithromycin, potentially important given its use as first-line empirical treatment, and indicates the need for improved surveillance of gonococcal AMR in LAC. Trial registration: Registered in PROSPERO, CRD42021253342.
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Antiinfecciosos , Gonorrea , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Neisseria gonorrhoeae , Azitromicina , América Latina/epidemiología , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiologíaRESUMEN
INTRODUCTION: Rotavirus (RV) is the most common cause of childhood diarrhea. Argentina introduced RV vaccination in the National Immunization Program in January 2015. This study evaluates the impact of RV vaccine implementation on the burden of acute diarrheal disease (ADD) and RV positive cases, and hospitalizations among children in Argentina. METHODS: A counterfactual time-series analysis was performed. Data on ADD (2013-2018) and RV diarrhea (2012-2018) cases in children aged < 5 years were collected from the National Healthcare Surveillance System (clinical and laboratory data). Data on hospital discharges following ADD and RV diarrhea (2011-2017) were retrieved from the Health Statistics and Information Office. All data were classified by the age groups < 1 year, < 2 years, 2-5 years. Vaccine impact was defined as the difference between the predicted time trend (simulated using 2012-2014 data) and the actual post-vaccination data (2015-2018). RESULTS: A significant reduction of 22.1% of notified ADD cases and 15.4% of hospital discharges following ADD among children < 2 years was observed in the 3 years after RV vaccine implementation. Data also showed a significant decline of 54.0% and 59.4% of notified RV cases in children < 2 and < 1 years, respectively, and a reduction of 39.3% and 40.8% in RV hospital discharges for the same age groups. CONCLUSION: This study shows a significant reduction in notified ADD cases and RV cases and hospital discharges following ADD and RV cases in children < 2 years after RV vaccine introduction in Argentina in 2015.
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Invasive meningococcal disease (IMD) is an uncommon yet unpredictable, severe, and life-threatening disease with the highest burden in young children. In Chile, most IMD is caused by meningococcal serogroup B (MenB) and W (MenW) infection. In response to a MenW outbreak in 2012, a toddler vaccination program was implemented using quadrivalent meningococcal conjugate vaccine against serogroups A, C, W and Y (MenACWY). The vaccine program, however, does not protect infants or other unvaccinated age groups and does not protect against MenB IMD. Since 2017, MenB IMD cases are becoming increasingly prevalent. Using a dynamic transmission model adapted for Chile, this analysis assessed the public health impact (reduction in IMD cases, long-term sequelae, deaths, and quality-adjusted life-years) of six alternative vaccination strategies using MenACWY and/or the four-component MenB (4CMenB) vaccine in infants, toddlers, and/or adolescents compared to the National Immunization Program (NIP) implemented in 2014. Strategies that added infant 4CMenB to MenACWY in toddlers or adolescents would prevent more IMD than the current NIP, observed within the first 5 years of the program. Replacing the NIP by an adolescent MenACWY strategy would prevent more IMD in the longer term, once herd immunity is established to protect unvaccinated infants or older age groups. The strategy that maximized reduction of IMD cases and associated sequelae in all age groups with immediate plus long-term benefits included infant 4CMenB and MenACWY in both toddlers and adolescents. This analysis can help policymakers determine the best strategy to control IMD in Chile and improve public health. A set of audio slides linked to this manuscript can be found at https://doi.org/10.6084/m9.figshare.16837543.
Plain Language Summary (PLS)What is the context?Invasive meningococcal disease (IMD) is a severe, sometimes fatal, unpredictable disease with highest rates in infants, young children, and adolescents. It is caused by different serogroups of Neisseria meningitidis bacteria. Most cases in Chile are due to meningococcal serogroups B (MenB) and W (MenW). Following a MenW IMD outbreak in 2012, vaccination was introduced, leading to the current National Immunization Program (NIP) in toddlers with quadrivalent meningococcal conjugate vaccine (MenACWY) (protecting against IMD caused by MenA, C, W, and Y).What is new?A disease model to predict the impact of vaccination strategies in the Chilean population compared six alternative strategies, using the multi-component MenB (4CMenB) vaccine for infants (protecting against MenB, with potential cross-protection against MenW and Y IMD) and/or the MenACWY vaccine for toddlers and/or adolescents.What is the impact?Results, compared to the NIP, show that: Strategy 1 (a program targeting only infants with 4CMenB) would reduce more MenB cases but fewer MenA, C, W and Y cases resulting in a lower reduction of total IMD cases in the long term; Strategy 3 (a program targeting only adolescents with MenACWY) would have a similar effect to the NIP in the short term but a far greater IMD reduction in the long term (as vaccinating this age group eventually reduces transmission to other age groups, reducing their risk of disease); all the other strategies targeted more than one age group, further reducing numbers of IMD cases compared with the NIP. The greatest benefits were seen with infant 4CMenB vaccination combined with toddler and adolescent MenACWY vaccination. Results can help policymakers determine the best IMD strategy to maximize the benefits of available meningococcal vaccines.
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Infecciones Meningocócicas , Vacunas Meningococicas , Adolescente , Anciano , Preescolar , Chile/epidemiología , Progresión de la Enfermedad , Humanos , Programas de Inmunización , Lactante , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Salud Pública , Vacunación , Vacunas ConjugadasRESUMEN
OBJECTIVES: To identify the most cost-efficient combination of pneumococcal vaccines in infants and aging adults for a 10-year period in Brazil. METHODS: Constrained optimization (CO) prioritized 9 pneumococcal vaccine regimens according to their gain in quality-adjusted life-years (QALYs) and their related costs over a prespecified time horizon with defined constraints for 2 age groups, infants and aging adults. The analysis starts from the current universal infant vaccination of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), 2 primary and 1 booster dose at 2, 4, and 12 months, respectively. Key constraints are the fixed annual vaccine budget increase and the relative return on investment (ROIR) per regimen, which must be > 1, the reference intervention being the current vaccination strategy in infants and the most cost-efficient one in aging adults. RESULTS: The CO analysis including all the constraints indicates that over 10 years the maximum extra health gain is 126 194 QALYs for an extra budget of $974 million Brazilian reals (ROIR = 1.15). Results could be improved with a higher proportion of the at-risk population in aging adults, less herd effect, and better QALY scores. CONCLUSION: The study shows that with 4 constraints on budget, time horizon, vaccine coverage, and cost efficiency, a CO analysis could identify the most cost-efficient overall pneumococcal vaccination strategy for Brazil, allowing for limited vaccine budget increase while obtaining appropriate health gain.
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Infecciones Neumocócicas , Adulto , Brasil , Humanos , Lactante , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Vacunación , Vacunas ConjugadasRESUMEN
Liver cancer is one of the main causes of death related to cancer worldwide; its etiology is related with infections by C or B hepatitis virus, alcohol consumption, smoking, obesity, nonalcoholic fatty liver disease, diabetes, and iron overload, among other causes. Several kinds of primary liver cancer occur, but we will focus on hepatocellular carcinoma (HCC). Numerous cellular signaling pathways are implicated in hepatocarcinogenesis, including YAP-HIPPO, Wnt-ß-catenin, and nuclear factor-κB (NF-κB); these in turn are considered novel therapeutic targets. In this review, the role of lipid metabolism regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in the development of HCC will also be discussed. Moreover, recent evidence has been obtained regarding the participation of epigenetic changes such as acetylation and methylation of histones and DNA methylation in the development of HCC. In this review, we provide detailed and current information about these topics. Experimental models represent useful tools for studying the different stages of liver cancer and help to develop new pharmacologic treatments. Each model in vivo and in vitro has several characteristics and advantages to offer for the study of this disease. Finally, the main therapies approved for the treatment of HCC patients, first- and second-line therapies, are described in this review. We also describe a novel option, pirfenidone, which due to its pharmacological properties could be considered in the future as a therapeutic option for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinogénesis , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Modelos Teóricos , PPAR gammaRESUMEN
BACKGROUND: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD), community-acquired pneumonia (CAP) and acute otitis media (AOM). Two higher-valent pneumococcal conjugate vaccines (PCV) are available, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV-13). This study estimated the economic and health impact of PHiD-CV vaccination on pneumococcal disease burden in children <5 years of age in Brazil. METHODS: The disease burden prior to the PHiD-CV vaccination program was estimated from literature and databases. The effect of PHiD-CV was estimated as a reduction of 70% for IPD, 26% for CAP and 40% for AOM, based on published studies. Residual IPD cases attributable to serotype 19A were estimated using surveillance data. PCV-13 effectiveness against 19A-IPD was set at 30%-70% higher than PHiD-CV. Vaccine prices were US$12.85/dose for PHiD-CV and US$14.50/dose for PCV-13. RESULTS: PHiD-CV vaccination reduced IPD by 6359, CAP by 315,016 and AOM by 669,943 cases, with estimated cost savings of >US$84 million annually and US$211-22,232 per case averted depending on the outcome. Switching from PHiD-CV to PCV-13 would avoid only a few additional IPD cases at additional costs exceeding US$18 million per year (US$125,192-386,230 per IPD case averted). CONCLUSIONS: The PHiD-CV vaccination program in Brazil has resulted in important reductions of pneumococcal disease and substantial cost savings. Instead of switching PCVs, expanding vaccine coverage or investing in other health care interventions would be a more efficient use of resources to improve the health of the population in Brazil.
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Costo de Enfermedad , Programas de Inmunización/economía , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/economía , Brasil , Preescolar , Costos y Análisis de Costo , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Infecciones Neumocócicas/economíaRESUMEN
Atrazine (ATZ) is an herbicide which is applied to the soil, and its mechanism of action involves the inhibition of photosynthesis. One of its main functions is to control the appearance of weeds in crops, primarily in corn, sorghum, sugar cane, and wheat; however, it is very toxic for numerous species, including humans. Therefore, this work deals with the adsorption of ATZ from aqueous solutions using nanocomposite materials, synthesized with two different types of organo-modified clays. Those were obtained by the free radical polymerization of 4-vinylpyridine (4VP) and acrylamide (AAm) in different stoichiometric ratios, using tetrabutylphosphonium persulfate (TBPPS) as a radical initiator and N,N'-methylenebisacrylamide (BIS) as cross-linking agent. The structural, morphological, and textural characteristics of clays, copolymers, and nanocomposites were determined through different analytical and instrumental techniques, i.e., X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Adsorption kinetics experiments of ATZ were determined with the modified and synthesized materials, and the effect of the ratio between 4VP and AAm moieties on the removal capacities of the obtained nanocomposites was evaluated. Finally, from these sets of experiments, it was demonstrated that the synthesized nanocomposites with higher molar fractions of 4VP obtained the highest removal percentages of ATZ.
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In a recent article, Wasserman et al. estimated and forecasted the health and economic impact of switching from the 13-valent (PCV-13) to the 10-valent (PHiD-CV) pneumococcal conjugate vaccine in Mexico's national immunization program. In this response letter, we highlight various methodological inconsistencies and model input considerations that potentially bias the results and further recommendations made by the authors.
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Infecciones Neumocócicas , Análisis Costo-Beneficio , Humanos , México , Vacunas Neumococicas , Vacunas ConjugadasRESUMEN
OBJECTIVE: To estimate the cost effectiveness associated with the use of pneumococcal conjugated vaccines, Prevenar-13 and Synflorix®, in the Mexican pediatric population. METHODS: The cost-effectiveness ratio of instrumenting vaccination programs based upon the use of Prevenar-13 and Synflorix® in the Mexican pediatric population was estimated by using a Markov's simulation model. The robustness of the conclusions reached on cost-effectiveness for both vaccines was assayed through an univariate and probabilistic sensitivity analysis that included all of the parameters considered by the model. RESULTS: Synflorix® was dominant over Prevenar-13 in the cost-utility analysis; the former generated more quality-adjusted life years at a lower cost and with a lower incremental cost-utility ratio. Based on the cost-effective analysis, Prevenar-13 generated more life years gained but at a higher cost. The use of Prevenar-13 originated a higher incremental cost-effectiveness ratio and, therefore, it was not cost-effective as compared with Synflorix®. CONCLUSIONS: Even though the simulations for Prevenar-13 and Synflorix® revealed both of them to be cost-effective when used to instrument pediatric vaccination campaigns in Mexico, Synflorix® had a better cost-utility/effectiveness profile. In addition, although Prevenar-13 and Synflorix® produced equivalent health outcomes, the overall analysis predicted that Synflorix® would save 360 million Mexican pesos, as compared with Prevenar-13.
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Vacuna Neumocócica Conjugada Heptavalente/economía , Infecciones Neumocócicas/prevención & control , Años de Vida Ajustados por Calidad de Vida , Análisis Costo-Beneficio , Vacuna Neumocócica Conjugada Heptavalente/uso terapéutico , Humanos , Lactante , México , Infecciones Neumocócicas/economía , Vacunas Neumococicas/economía , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae , Vacunación , Vacunas ConjugadasRESUMEN
Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoantibodies were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of the disease. The overall aim of this study was to characterize the reactivity of different isotypes of autoantibodies against carbamylated antigens of vimentin in relation to established rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA. Antigenic properties of carbamylated vimentin as well as vimentin peptides were analyzed in 101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor, anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %) and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was associated with positive IgG antibody reactivity against CCP2 in 75.0 % and against MCV in 90 % of patients. Furthermore, IgM antibody response against carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the combination of ACPA with anti-carbVIM IgM provided the best diagnostic performance so far achieved in a RA cohort of this ethnic origin. We demonstrate a high prevalence of anti-carbVIM antibodies and correlation with smoking in Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker in ACPA-negative patients and, in combination with ACPA IgG assays, optimizes the strategy for autoantibody testing.
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Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Autoantígenos/inmunología , Inmunoglobulina M/sangre , Vimentina/inmunología , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/etnología , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Cuba/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Estudios Seroepidemiológicos , Pruebas Serológicas , Fumar/efectos adversos , Fumar/sangre , Fumar/inmunologíaRESUMEN
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Linfocitos B/inmunología , Citocinas/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Artritis Reumatoide/patología , Linfocitos B/patología , Método Doble Ciego , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Linfocitos T/patologíaRESUMEN
Implementation of cervical cancer (CC) vaccination in Latin America is expected to reduce the high CC burden in those countries. But the efficiency of such vaccination programs in the region still remains unknown. This study assesses the cost-effectiveness and cost-utility of introducing vaccination into the current CC disease management of five Latin American countries (Argentina, Brazil, Chile, Mexico, and Peru). The modelling results indicate that universal mass vaccination is cost-effective in the current health care setting of each country (<3x gross domestic product per capita, per country) with a substantial number of CC cases and deaths avoided in addition to an increase of quality-adjusted life years. This study will help guide the design of future clinical programmes and health-related policies. It will assist early and effective decision-making processes related to vaccine implementation in Latin America.
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Vacunas contra el Cáncer/economía , Programas de Inmunización/economía , Modelos Económicos , Vacunas contra Papillomavirus/economía , Análisis Costo-Beneficio , Femenino , Humanos , América Latina , Infecciones por Papillomavirus/prevención & control , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
Group A rotaviruses are one of the most frequently detected viral agents associated with neonatal diarrhea in piglets. In order to characterize rotavirus (RV) strains circulating in Argentinean swine, four porcine production farms located in Buenos Aires were studied. RV strains genotyped as P[6]G4, P[6]G8 and P[1]G6 were found in piglets under 30 days of age, without diarrhea. Phylogenetic and sequence analysis of the VP7 gene from G4 strains available in databases, reveals five porcine new lineages (III-VII) and three sublineages (VIIa-VIIc). The G4 porcine Argentinean strains were grouped with a porcine RV strain isolated in Brazil and another RV strain isolated from a child with diarrhea in Mexico, constituting an American lineage (VII). On the other hand, porcine G6 and G8 were closely related to RV's circulating in Argentinean cattle and South-American camelids, respectively. The fact that G4 porcine lineages were epidemiologically related to human strains, and G6 and G8 Argentinean porcine strains were found related to bovine and South-American camelids, respectively, suggests that pigs might play a crucial role as reservoir and generator of newly adapted emerging RV strains for human and other species.