Development of SCAR Markers for Genetic Authentication of Metarhizium acridum.

In this study, molecular typing using Randomly Amplified Polymorphic DNA (RAPD-PCR) was conducted on 16 original isolates of Metarhizium acridum obtained from locusts (Schistocerca piceifrons ssp. piceifrons.) in Mexico (MX). The analysis included reference strains of the genus Metarhizium sourced from various geographical regions. The isolates were identified by phenotypic (macro and micromorphology) and genotypic methods (RAPD-PCR and Amplified Fragment Length Polymorphisms (AFLP), through a multidimensional analysis of principal coordinates (PCoA) and a minimum spanning network (MST). Subsequently, Sequences-Characterized Amplified Region (SCAR) markers were developed for the molecular detection of M. acridum, these markers were chosen from polymorphic patterns obtained with 14 primers via RAPD-PCR. Phenotypic and genotypic characterization identified the MX isolates as M. acridum. Of all the polymorphic patterns obtained, only OPA04 and OPA05 were chosen, which presented species-specific bands for M. acridum, and further utilized to create SCAR markers through cloning and sequencing of the specific bands. The specificity of these two markers was confirmed via Southern hybridization. The SCAR markers (Ma-160OPA-05 and Ma-151OPA-04) exhibit remarkable sensitivity, detecting down to less than 0.1 ng, as well as high specificity, as evidenced by their inability to cross-amplify or generate amplification with DNAs from other strains of Metarhizium (as Metarhizium anisopliae) or different genera of entomopathogenic fungi (Cordyceps fumosorosea and Akanthomyces lecanii). These SCAR markers yield readily detectable results, showcasing high reproducibility. They serve as a valuable tool, especially in field applications.

Remarkable Phenotypic Virulence Factors of Microsporum canis and Their Associated Genes: A Systematic Review.

Microsporum canis is a widely distributed dermatophyte, which is among the main etiological agents of dermatophytosis in humans and domestic animals. This fungus invades, colonizes and nourishes itself on the keratinized tissues of the host through various virulence factors. This review will bring together the known information about the mechanisms, enzymes and their associated genes relevant to the pathogenesis processes of the fungus and will provide an overview of those virulence factors that should be better studied to establish effective methods of prevention and control of the disease. Public databases using the MeSH terms "Microsporum canis", "virulence factors" and each individual virulence factor were reviewed to enlist a series of articles, from where only original works in English and Spanish that included relevant information on the subject were selected. Out of the 147 articles obtained in the review, 46 were selected that reported virulence factors for M. canis in a period between 1988 and 2023. The rest of the articles were discarded because they did not contain information on the topic (67), some were written in different languages (3), and others were repeated in two or more databases (24) or were not original articles (7). The main virulence factors in M. canis are keratinases, fungilisins and subtilisins. However, less commonly reported are biofilms or dipeptidylpeptidases, among others, which have been little researched because they vary in expression or activity between strains and are not considered essential for the infection and survival of the fungus. Although it is known that they are truly involved in resistance, infection and metabolism, we recognize that their study could strengthen the knowledge of the pathogenesis of M. canis with the aim of achieving effective treatments, as well as the prevention and control of infection.

Quantifying water-use efficiency in plant canopies with varying leaf angle and density distribution.

BACKGROUND AND AIMS: Variation in architectural traits related to the spatial and angular distribution of leaf area can have considerable impacts on canopy-scale fluxes contributing to water-use efficiency (WUE). These architectural traits are frequent targets for crop improvement and for improving the understanding and predictions of net ecosystem carbon and water fluxes. METHODS: A three-dimensional, leaf-resolving model along with a range of virtually generated hypothetical canopies were used to quantify interactions between canopy structure and WUE by examining its response to variation of leaf inclination independent of leaf azimuth, canopy heterogeneity, vegetation density and physiological parameters. KEY RESULTS: Overall, increasing leaf area index (LAI), increasing the daily-averaged fraction of leaf area projected in the sun direction (Gavg) via the leaf inclination or azimuth distribution and increasing homogeneity had a similar effect on canopy-scale daily fluxes contributing to WUE. Increasing any of these parameters tended to increase daily light interception, increase daily net photosynthesis at low LAI and decrease it at high LAI, increase daily transpiration and decrease WUE. Isolated spherical crowns could decrease photosynthesis by ~60 % but increase daily WUE ≤130 % relative to a homogeneous canopy with equivalent leaf area density. There was no observed optimum in daily canopy WUE as LAI, leaf angle distribution or heterogeneity was varied. However, when the canopy was dense, a more vertical leaf angle distribution could increase both photosynthesis and WUE simultaneously. CONCLUSIONS: Variation in leaf angle and density distributions can have a substantial impact on canopy-level carbon and water fluxes, with potential trade-offs between the two. These traits might therefore be viable target traits for increasing or maintaining crop productivity while using less water, and for improvement of simplified models. Increasing canopy density or decreasing canopy heterogeneity increases the impact of leaf angle on WUE and its dependent processes.

Factors Associated with Candidiasis in Pemphigus Vulgaris Patients: Results from a Retrospective Study in Two Second-Care Level Hospitals in Mexico.

BACKGROUND: Infections are a major cause of morbidity and mortality in patients with pemphigus vulgaris (PV). One of the most common infections in these patients is candidiasis. This is probably due to the use of systemic immunosuppressants, including oral and intravenous corticosteroids, mainly in megadoses (pulse therapy), although it is unknown if there are other associated factors, in addition to immunosuppressive treatment. We determine the factors associated with candidiasis in PV patients in two second-care level hospitals in Mexico. METHODS: We reviewed 100 cases with PV. Cases were randomly selected from the databases of two second-care level hospitals between January 2010 and December 2019 (10 years). The primary endpoint was the incidence of candidiasis in patients with PV. RESULTS: One hundred patients with PV were enrolled in this retrospective study. Candidiasis was observed in 79 patients (79%). A maximum corticosteroid dose of 55 mg/day during the last year (p = 0.001) and a higher neutrophil/lymphocyte ratio were associated with candidiasis in patients with PV (p = 0.001). CONCLUSION: Risk factors favoring candidiasis in patients with PV are not only related to the use of corticosteroids, but also to demographic factors, the activity of the disease, and the systemic inflammation associated with autoimmunity.

Clinical Cases of Coccidioidomycosis in the Americas in the Period 1950-2021: Epidemiology Data, Diagnosis, and Treatment.

Coccidioidomycosis, caused by Coccidioides immitis and C. posadasii, causes significant morbidity and mortality, both in immunocompetent and immunocompromised people, mainly in endemic areas. The present work analyzed its epidemiology, diagnostic methods, and treatment by reviewing clinical cases published from 1950 to 2021. Fifty-nine articles were included, corresponding to 275 clinical cases. The results showed a higher incidence of coccidioidomycosis in the male gender than the female gender. The most affected age group was 31-40 years, and the most reported clinical presentation was disseminated with greater involvement in cutaneous and subcutaneous tissue, followed by the CNS, bone system, and peritoneum. The species most frequently reported was C. immitis. The most used treatment was azoles, followed by their combination with amphotericin B, monotherapy with amphotericin B, and alternative medicine. This work shows that epidemiological data outside the USA are still scarce. Serological tests are the preferred diagnostic method in daily medical practice, and cultures remain the gold standard. The treatment for coccidioidomycosis is ketoconazole and amphotericin B, individually or in combination.

Acute Myopericarditis Secondary to Chagas Disease.

American trypanosomiasis or Chagas disease is predominantly a vector-borne multisystemic infection caused by Trypanosoma cruzi, a protozoan parasite transmitted by triatomine bugs in endemic areas such as Mexico and Central and South America. Acute T. cruzi infection is mostly asymptomatic, nonetheless, in up to one-third of the patients, a mild form of the disease can be present, with nonspecific manifestations like fever, lymphadenopathy, hepatosplenomegaly, inflammation at the inoculation site (inoculation chancre) and unilateral palpebral edema (Romaña sign). Severe acute disease occurs in less than 1% of patients and includes myopericarditis and meningoencephalitis. If untreated, the acute phase can cause chronicity with cardiac and gastrointestinal involvement. We report the case of a female with occupational exposure to this parasite, who presented with acute myopericarditis, a rare form of presentation of this disease.

Survival of Hemophagocytic Syndrome Secondary to Fungal and Bacterial Infection in a Pediatric Patient with HIV: A Case Report.

HIV-associated hemophagocytic lymphohistiocytosis (HLH) is mainly due to infections caused by viruses, fungi, and, to a lesser extent, bacteria, often with fatal results. Case presentation: A 15-year-old pediatric patient from another institution was admitted to our hospital with a fever of unknown origin (FUO). Clinical analysis and laboratory studies diagnosed HIV infection. The approach to an FUO in a patient with AIDS is much more complex due to the search for common etiologies and opportunistic infections. In this case, disseminated histoplasmosis, pulmonary tuberculosis, pneumocystosis, and ehrlichiosis were diagnosed, prompting an urgent and comprehensive approach to prevent mortality. Due to the multiple infections, HLH was triggered. An early intervention with trimethoprim (TMP)-sulfamethoxazole (SMX), liposomal amphotericin B, doxycycline, and quadruple antiphimic therapy to suppress infections, in conjunction with the early administration of HLH treatment, favored the survival of this patient.

Association of women-specific health factors in the severity of Parkinson's disease.

Parkinson's disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, there is little known about the role that fluctuations in hormones and immune responses from sex-specific health experiences have in the disease's development and severity. We sought to identify women-specific health experiences associated with PD severity, after adjusting for known PD factors, by developing and distributing a women-specific questionnaire across the United States and creating multivariable models for PD severity. We created a questionnaire that addresses women's specific experiences and their PD clinical history and deployed it through The Parkinson's Foundation: PD Generation. To determine the association between women-specific health factors and PD severity, we constructed multivariable logistic regression models based on the MDS-UPDRS scale and the participants' questionnaire responses, genetics, and clinical data. For our initial launch in November 2021, we had 304 complete responses from PD GENEration. Univariate and multivariate logistic modeling found significant associations between major depressive disorder, perinatal depression, natural childbirth, LRRK2 genotype, B12 deficiency, total hysterectomy, and increased PD severity. This study is a nationally available questionnaire for women's health and PD. It shifts the paradigm in understanding PD etiology and acknowledging how sex-specific experiences may contribute to PD severity. In addition, the work in this study sets the foundation for future research to investigate the factors behind sex differences in PD.

Alfabetización en medios para promover la satisfacción corporal y la alimentación saludable en adolescentes / Media literacy to promote body satisfaction and healthy eating in adolescents

Resumen Este estudio evaluó la eficacia de un programa de alfabetización en medios (AM) para promover la satisfacción corporal y la alimentación saludable en adolescentes de 12 a 15 años de edad. Es un estudio cuantitativo, cuasiexperimental y longitudinal, con preprueba y postprueba. Participaron 30 mujeres adolescentes de 12-15 años de edad, asignadas aleatoriamente a una de dos condiciones: programa de AM (n = 16) y grupo control en lista de espera (n = 14). Las participantes completaron, en preprueba y postprueba, el Cuestionario de Actitudes hacia la Apariencia Física (SATAQ-3), el Cuestionario de Evitación de la Imagen Corporal (BIAQ) y el Cuestionario de Comportamiento Alimentario (CCA). Hubo una disminución en las puntuaciones obtenidas por el grupo con intervención. Las participantes reportaron comparar menos su cuerpo con relación al cuerpo de las personas que son atléticas (F = 4.17, p = .05), las participantes también consideraron, al finalizar la intervención, que las personas famosas no son una fuente importante de información sobre la moda y sobre cómo ser atractiva (F = 6.87, p = .01). Los programas de AM son herramientas socioeducativas útiles para prevenir la insatisfacción corporal y los comportamientos alimentarios de riesgo, así como para promover conductas saludables.

Abstract This study evaluated the effectiveness of a media literacy (ML) program to promote body satisfaction and healthy eating in adolescents from 12 to 15 years old. The study is quantitative, quasi-experimental and longitudinal study, with pre-test and final post-test. Participated 30 female adolescents aged from 12 to 15 years old, randomly assigned to one of two conditions: ML program (n = 16) and control group on the waiting list (n = 14), who answered the Attitudes to the Physical Appearance Questionnaire (SATAQ-3), the Body Image Avoidance Questionnaire (BIAQ) and the Eating Behavior Questionnaire (CCA). The participants reported comparing their body less with respect to the body of people who are athletic (F = 4.17, p = .05), the participants also considered, at the end of the intervention, that famous people are not an important source of information about fashion and how to be attractive (F = 6.87, p = .01). ML programs are useful socio-educational tools to prevent problems such as dissatisfaction with body image and risky eating behaviors, or to promote healthy behaviors.

Phenotypic and Genotypic Identification of Dermatophytes from Mexico and Central American Countries.

Dermatophytes are fungi included in the genera Trichophyton, Microsporum, Epidermophyton, Nannizzia, Paraphyton, Lophophyton, and Arthroderma. Molecular techniques have contributed to faster and more precise identification, allowing significant advances in phylogenetic studies. This work aimed to identify clinical isolates of dermatophytes through phenotypic (macro- and micromorphology and conidia size) and genotypic methods (sequences of ITS regions, genes of ß tubulin (BT2), and elongation factor α (Tef-1α)) and determine the phylogenetic relationships between isolates. Ninety-four dermatophyte isolates from Costa Rica, Guatemala, Honduras, Mexico, and the Dominican Republic were studied. The isolates presented macro- and micromorphology and conidia size described for the genera Trichophyton, Microsporum, and Epidermophyton. Genotypic analysis classified the isolates into the genera Trichophyton (63.8%), Nannizzia (25.5%), Arthroderma (9.6%), and Epidermophyton (1.1%). The most frequent species were T. rubrum (26 isolates, 27.6%), T. interdigitale (26 isolates, 27.6%), and N. incurvata (11 isolates, 11.7%), N. gypsea and A. otae (nine isolates, 9.6%), among others. The genotypic methods clarified the taxonomic status of closely related species. For instance, the ITS and BT2 markers of T. rubrum/T. violaceum did not differ but the Tef-1α gene did. On the other hand, the three markers differed in T. equinum/T. tonsurans. Therefore, the ITS, BT2, and Tef-1α genes are useful for typing in phylogenetic analyses of dermatophytes, with Tef-1α being the most informative locus. It should be noted that isolate MM-474 was identified as T. tonsurans when using ITS and Tef-1α, but when using BT2, it was identified as T. rubrum. On the other hand, no significant difference was found when comparing the methods for constructing phylogenies, as the topologies were similar.

Aspergillus-SARS-CoV-2 Coinfection: What Is Known?

COVID-19-associated pulmonary aspergillosis (CAPA) has had a high incidence. In addition, it has been associated with prolonged hospital stays, as well as several predisposing risk factors, such as fungal factors (nosocomial organism, the size of the conidia, and the ability of the Aspergillus spp. of colonizing the respiratory tract), environmental factors (remodeling in hospitals, use of air conditioning and negative pressure in intensive care units), comorbidities, and immunosuppressive therapies. In addition to these factors, SARS-CoV-2 per se is associated with significant dysfunction of the patient's immune system, involving both innate and acquired immunity, with reduced CD4+ and CD8+ T cell counts and cytokine storm. Therefore, this review aims to identify the factors influencing the fungus so that coinfection with SARS-CoV-2 can occur. In addition, we analyze the predisposing factors in the fungus, host, and the immune response alteration due to the pathogenicity of SARS-CoV-2 that causes the development of CAPA.

HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1.

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.

Frequency of Candida spp. in the Oral Cavity of Asymptomatic Preschool Mexican Children and Its Association with Nutritional Status.

Malnutrition is a public health problem in developing countries, affecting the child population, which favors the appearance of infections such as oral candidiasis. In Mexico, information on the presence of oral colonization by Candida spp. in asymptomatic children is scarce. The present study aimed to determine the presence of Candida spp. in the oral cavity of asymptomatic preschool Mexican children and its association with their nutritional status. A sample of oral mucosa was obtained using a sterile swab and then inoculated in Sabouraud dextrose agar with antibiotics, and the yeast growth was phenotypically identified. The anthropometric profile of children was performed based on the guidelines of the International Society for the Advancement of Kinanthropometry. In addition, eating habits were investigated. The possible associations between the variables were determined through the chi-square test (IC95%, p < 0.05) (GraphPad Prism 8.0). Among the 743 assessed children (403 boys and 340 girls), the average age was 4.6 years, and the average nutritional status was normal (53.7%), followed by undernutrition (28.4%), overweight (12.4%) and obesity (5.5%). In 52 children, Candida was isolated, and the identified species were C. albicans (87.8%), C. glabrata (11.5%), C. krusei (5.8%) and C. parapsilosis (1.9%). The frequency of colonization was greater in males of six years (69.23%). There was no significant association between the colonization by Candida spp. and the nutritional status; however, a relation was observed with a high intake of simple carbohydrates.

Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers.

Adjuvanted nanocarrier-based vaccines hold substantial potential for applications in novel early-life immunization strategies. Here, via mouse and human age-specific in vitro modeling, we identified the combination of a small-molecule STING agonist (2'3'-cyclic GMP-AMP, cGAMP) and a TLR7/8 agonist (CL075) to drive the synergistic activation of neonatal dendritic cells and precision CD4 T-helper (Th) cell expansion via the IL-12/IFNγ axis. We further demonstrate that the vaccination of neonatal mice with quadrivalent influenza recombinant hemagglutinin (rHA) and an admixture of two polymersome (PS) nanocarriers separately encapsulating cGAMP (cGAMP-PS) and CL075 (CL075-PS) drove robust Th1 bias, high frequency of T follicular helper (TFH) cells, and germinal center (GC) B cells along with the IgG2c-skewed humoral response in vivo. Dual-loaded cGAMP/CL075-PSs did not outperform admixed cGAMP-PS and CL075-PS in vivo. These data validate an optimally designed adjuvantation system via age-selected small-molecule synergy and a multicomponent nanocarrier formulation as an effective approach to induce type 1 immune responses in early life.

Selection of Polymorphic Patterns Obtained by RAPD-PCR through Qualitative and Quantitative Analyses to Differentiate Aspergillus fumigatus.

The objective of this work was to use the random amplification of the polymorphic DNA-polymerase chain reaction (RAPD-PCR) technique to select polymorphic patterns through qualitative and quantitative analyses to differentiate the species A. flavus, A. fumigatus, A. niger and A. tubingensis. Twenty-seven Aspergillus isolates from different species were typified using phenotypic (macro- and micromorphology) and genotypic (partial BenA gene sequencing) methods. Thirty-four primers were used to obtain polymorphic patterns, and with these a qualitative analysis was performed to select the primers that presented species-specific patterns to distinguish each species. For the quantitative selection, a database was built from the polymorphic patterns and used for the construction of logistic regression models; later, the model that presented the highest value of sensitivity against specificity was evaluated through ROC curves. The qualitative selection showed that the primers OPA-19, P54, 1253 and OPA-02 could differentiate the species. A quantitative analysis was carried out through logistic regression, whereby a species-specific correlation of sensitivity and specificity greater than 90% was obtained for the primers: OPC-06 with a 96.32% match to A. flavus; OPF-01 with a 100% match to A. fumigatus; OPG-13 with a 98.01% match to A. tubingensis; and OPF-07 with a 99.71% match to A. niger. The primer OPF-01 discriminated the four species as well as closely related species. The quantitative methods using the selected primers allowed discrimination between species and showed their usefulness for genotyping some of the species of medical relevance belonging to the genus Aspergillus.

Vaccines Against COVID-19: A Review.

As a result of the COVID-19 pandemic, various joint efforts have been made to support the creation of vaccines. Different projects have been under development, of which some are in the clinical evaluation stage and others in are in phase III with positive results. The aim of this paper was to describe the current situation of the development and production of vaccines available to the population to facilitate future research and continue developing and proposing ideas for the benefit of the population. So, we carried out a systematic review using databases such as PubMed, ScienceDirect, SciELO, and MEDLINE, including keywords such as "vaccines," "COVID-19," and "SARS-CoV-2". We reviewed the development and production of the anti-COVID vaccine and its different platforms, the background leading to the massive development of these substances, and the most basic immune aspects for a better understanding of their physiological activity and the immune response in those who receive the vaccine. We also analyzed immunization effects in populations with any medical or physiological conditions (such as immunosuppression, people with comorbidities, and pregnancy), as well as the response to immunization with heterologous vaccines and the hybrid immunity (the combination of natural immunity to SARS-CoV-2 with immunity generated by the vaccine). Likewise, we address the current situation in Mexico and its role in managing the vaccination process against SARS-CoV-2 at the national and international levels. There are still many clinical and molecular aspects to be described, such as the duration of active immunity and the development of immunological memory, to mention some of the most important ones. However, due to the short time since the global vaccination roll-out and that it has been progressive (not counting children and people with medical conditions), it is premature to say whether a second vaccination schedule will be necessary for the near future. Thus, it is essential to continue with health measures.

Detection and Molecular Identification of Eight Candida Species in Clinical Samples by Simplex PCR.

Systemic candidiasis is a frequent opportunistic mycosis that can be life-threatening. Its main etiological agent is Candida albicans; however, the isolation of non-albicans Candida species has been increasing. Some of these species exhibit greater resistance to antifungals, so the rapid and specific identification of yeasts is crucial for a timely diagnosis and optimal treatment of patients. Multiple molecular assays have been developed, based mainly on polymerase chain reaction (PCR), showing high specificity and sensitivity to detect and identify Candida spp. Nevertheless, its application in diagnosis has been limited due to specialized infrastructure or methodological complexity. The objective of this study was to develop a PCR assay that detects and identifies some of the most common pathogenic Candida species and evaluate their diagnostic utility in blood samples and bronchial lavage. A pair of oligonucleotides was designed, CandF and CandR, based on sequence analysis of the 18S-ITS1-5.8S-ITS2-28S region of the rDNA of Candida spp., deposited in GenBank. The designed oligonucleotides identified C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei/Pichia kudriazevii, C. guilliermondii/Meyerozyma guilliermondii, C. lusitaniae/Clavispora lusitaniae, and C. dubliniensis using simplex PCR based on the amplicon size, showing a detection limit of 10 pg/µL of DNA or 103 yeasts/mL. Based on cultures as the gold standard, it was determined that the sensitivity (73.9%), specificity (96.3%), and the positive (94.4%) and negative (81.2%) predictive values of the PCR assay with the designed oligonucleotides justify their reliable use in diagnosis.

Safety of primary immunization with a DTwP-HBV/Hib vaccine in healthy infants: a prospective, open-label, interventional, phase IV clinical study.

OBJECTIVE: This study aimed to assess the safety of a fully liquid DTwP-HBV/Hib pentavalent vaccine (EupentaTM) based on the occurrence of adverse events (AEs) following vaccination. METHODS: This was a prospective, open-label, single-arm, interventional phase IV study. A single intramuscular injection of the study vaccine was administered to infants at approximately 6, 10, and 14 weeks of age, and an end-of-study follow-up visit was scheduled at 18 weeks. RESULTS: In all, 3000 subjects were enrolled and received at least one dose of the study vaccine. Of these, 2717 (90.6%) experienced at least one AE. Immediate reactions, solicited and unsolicited AEs were respectively identified in 224 (7.5%), 2,652 (88.4%), and 1,099 (36.6%) subjects. The most prevalent solicited and unsolicited AEs comprised pain/tenderness and upper respiratory tract infection, respectively. Most AEs were mildly or moderately severe. Forty-one (1.4%) subjects had at least one serious AE (SAE); of these, two (0.1%) had two SAEs each, considered related to the study vaccine. Six (0.2%) subjects died due to unsolicited AEs, none of which were considered related to the study vaccine. No AEs were reported at the end-of-study follow-up visit. CONCLUSIONS: The study vaccine  had a safety profile similar to that reported in a previous clinical study, and did not result in an increased risk of AEs known to be associated with DTwP-based vaccines or previously unrecognized SAEs.