Search

We report a case of scrub typhus in a 54-year-old man who was bitten by several terrestrial leeches during a trip to Chiloé Island in southern Chile in 2006. A molecular sample, identified as related to Orientia tsutsugamushi based on the sequence of the16S rRNA gene, was obtained from a biopsy specimen of the eschar on the patient's leg. Serologic analysis showed immunoglobulin G conversion against O. tsutsugamushi whole cell antigen. This case and its associated molecular analyses suggest that an Orientia-like agent is present in the Western Hemisphere that can produce scrub typhus-like illness. The molecular analysis suggests that the infectious agent is closely related, although not identical, to members of the Orientia sp. from Asia. [ABSTRACT FROM AUTHOR]

Abstract Background Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). Methods This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. Results One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. Conclusions Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. Trial registration http://www.clinicaltrials.gov NCT00332566

Abstract Background Respiratory syncytial virus (RSV) is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide. High-risk infants currently receive RSV prophylaxis with palivizumab, a humanized RSV monoclonal antibody (MAb). In preclinical in vitro and in vivo (cotton-rat model) studies, motavizumab, a new RSV MAb, was shown to have greater anti-RSV activity than palivizumab. Motavizumab is currently under review for licensing approval. Since both MAbs may be available concurrently, this study evaluated their safety and tolerability when administered sequentially during the same RSV season. Methods Between April 2006 and May 2006, 260 high-risk infants were randomly assigned 1:1:1 to receive monthly intramuscular injections: 2 doses of motavizumab followed by 3 doses of palivizumab (M/P); 2 doses of palivizumab followed by 3 doses of motavizumab (P/M); or 5 doses of motavizumab (control). Adverse events (AEs, serious AEs [SAEs]), development of antidrug antibody (ADA), and serum drug trough concentrations were assessed. Results Most children received all 5 doses (246/260 [94.6%]) and completed the study (241/260 [92.7%]). While overall AE rates were similar (mostly level 1 or 2 in severity), SAEs and level 3 AEs occurred more frequently in the M/P group (SAEs: 22.9% M/P, 8.4% P/M, 11.8% motavizumab only; level 3 AEs: 15.7% M/P, 6.0% P/M, 6.5% motavizumab only). This trend in AE rates occurred before and after switching from motavizumab to palivizumab, suggesting a cause other than the combined regimen. Frequencies of AEs judged by the investigator to be related to study drug were similar among groups. Two deaths occurred on study (both in the M/P group, before palivizumab administration); neither was considered by the site investigator to be related to study drug. Mean serum drug trough concentrations were comparable among groups; ADA detection was infrequent (5.1% or less of any group). Conclusions The conclusions drawn from this study are limited by the small sample size per group. However, within this small study, overall AE rates, serum drug trough concentrations, and development of ADA associated with administering motavizumab and palivizumab sequentially to high-risk children appear comparable to administering motavizumab alone during the same RSV season. Trial Registration clinicaltrials.gov NCT00316264

Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus., Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac ® , were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4 + and CD8 + T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay., Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2 nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4 + T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects., Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4 + T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease., Clinical Trial Registration: clinicaltrials.gov #NCT04992260., Competing Interests: XM and QX are SINOVAC Biotech employees, contributed to the conceptualization of the study, and did not participate in the analysis or interpretation of the data presented in the manuscript. AS is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. AG is a consultant for Pfizer and Sanofi. La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rivera-Pérez, Méndez, Diethelm-Varela, Melo-González, Vázquez, Meng, Xin, Fasce, Fernández, Mora, Ramirez, Acevedo, Valiente-Echeverría, Soto-Rifo, Grifoni, Weiskopf, Sette, Astudillo, Le Corre, Abarca, Perret, González, Soto, Bueno and Kalergis.)

Immunocompetent adults with certain medical and behavioral factors are at increased risk of pneumococcal disease. In some countries, sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults. This subgroup analysis from a phase 3 study evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults 18-49 years of age with pre-defined risk factors for pneumococcal disease. Safety and immunogenicity post-vaccination were analyzed by type and baseline number of risk factors for pneumococcal disease (1 and ≥2 risk factors). This analysis included 1,131 participants randomized 3:1 to receive either V114 or PCV13, followed by PPSV23. The majority (73.1%) of participants had at least one risk factor. Safety and tolerability profiles of V114 and PCV13 were similar across risk factor groups. V114 administered either alone or sequentially with PPSV23 6 months later was immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of the number of baseline risk factors. V114 has the potential to broaden serotype coverage for at-risk adults.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac ® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac ® ; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac ® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Introduction: The human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples., Methods: PBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cell-derived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed., Results: Compared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-γ-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q., Conclusion: Immunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals., Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT03213405., Competing Interests: PG, SB, and AK hold a patent for the rBCG-N-hRSV vaccine with Pontificia Universidad Católica de Chile PCT/US2008/076682. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pacheco, Andrade, Gálvez, Vázquez, Rodríguez-Guilarte, Abarca, González, Bueno and Kalergis.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Thomas Weitzel, Constanza Martínez-Valdebenito, Katia Abarca, and Gerardo Acosta-Jamett report institutional support (including equipment and laboratory materials for diagnostic testing), travel support, and honoraria from the National Research and Development Agency of Chile (Agencia Nacional de Investigación y Desarrollo) and the National Fund for Scientific and Technological Development (Fondo Nacional de Desarrollo Científico y Tecnológico). No other potential conflicts of interest were disclosed.

Background: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster., Methods: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT., Findings: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4 + T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4 + T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found., Interpretation: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4 + T cell response may confer protection against the Omicron variant., Funding: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy., Competing Interests: Declaration of interests GZ and WM are SINOVAC Biotech employees and contributed to the conceptualization of the study (clinical protocol and eCRF design) and did not participate in the analysis or interpretation of the data presented in the manuscript. A.S. is a consultant for Gritstone Bio, Flow Pharma, ImmunoScape, Moderna, AstraZeneca, Avalia, Fortress, Repertoire, Gilead, Gerson Lehrman Group, RiverVest, MedaCorp, and Guggenheim. La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Scrub typhus is a potentially severe infection caused by bacteria of the genus Orientia, endemic in Asia-Pacific and recently discovered in southern Chile. The presented study aimed to determine the prevalence and species richness of rodent-associated trombiculid mites and their infection with Orientia spp. in different areas of two regions in southern Chile., Methodology/principal Findings: During summer 2020, trombiculid mites were collected from rodents captured in three areas in southern Chile known to be endemic for scrub typhus (Cochamó and Chiloé Island in the Los Lagos Region and Tortel in the Aysén Region). A total of 132 rodents belonging to five species were captured using Sherman-like traps; 89.4% were infested with trombiculids. Mite specimens were morphologically identified and subsequently tested by Orientia-specific qPCR. Six mite species were identified. Among chigger-infested rodents, 33.9% carried Orientia-positive mites; this rate was higher in Tortel (63.8%) than in Cochamó (45.0%) and Chiloé Island (2.0%). The analysis of individual mites (n = 901) revealed that 31.2% of Herpetacarus antarctica samples (n = 202) were positive for Orientia DNA; the prevalence was 7.0% in Paratrombicula neuquenensis (n = 213), 6.9% in Herpetacarus eloisae (n = 144), 3.6% in Argentinacarus expansus (n = 55), and 0% in Paratrombicula goffi (n = 110) and Quadraseta chiloensis (n = 177). The southernmost site (Tortel) showed the highest rates of trombiculid infestation, trombiculid load, and Orientia infection in the captured rodents., Conclusions/significance: Our study provides new insights into the trombiculid fauna and prevalence of Orientia in mites collected from wild rodents in southern Chile. Orientia DNA was detected in four of the six mite species. Rates of infestation, mite loads, and Orientia prevalences differed geographically and were highest in the Aysén Region. Our data improve our knowledge on possible vectors of scrub typhus and their distribution in Chile., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Silva de la Fuente et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4 + T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4 + T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4 + T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4 + T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4 + T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. IMPORTANCE CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4 + T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac ® , an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac ® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac ® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

Scrub typhus is a potentially severe rickettsiosis, caused by Orientia tsutsugamushi in the Asia-Pacific region. Recently, however, two distinct pathogens, " Candidatus Orientia chuto" and " Candidatus Orientia chiloensis", have been discovered in the Middle East and South America, respectively. Since the novel pathogens differ significantly from O. tsutsugamushi , many established diagnostic methods are unreliable. This work describes the development and validation of a new quantitative real-time PCR (qPCR) assay (Orien16S) for the detection of all known Orientia species. Based on a 94 bp sequence of the 16S rRNA gene ( rrs ), Orien16S recognized DNA samples from O. tsutsugamushi ( n = 41), Ca. O. chiloensis ( n = 5), and Ca. O. chuto ( n = 1), but was negative for DNA preparations from closely related rickettsiae and other members of the order Rickettsiales ( n = 22) as well as unrelated bacterial species ( n = 11). After its implementation in Chile, the assay was verified, correctly identifying all tested eschar and buffy coat samples ( n = 28) of clinical suspected cases. Furthermore, Orien16S detected Orientia DNA in trombiculid mites collected in endemic regions in southern Chile. The presented novel qPCR assay provides a useful tool for detecting Orientia and diagnosing scrub typhus from all geographical regions., Competing Interests: JJ and AR are employed by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Martínez-Valdebenito, Weitzel, Farris, Acosta-Jamett, Abarca and Richards.)

Background: Adults with certain medical and behavioral factors are at increased risk for pneumococcal disease (PD). Sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults in some countries., Methods: This phase 3 trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults aged 18-49 years with or without predefined risk factors for PD (NCT03547167). Overall, 1515 participants were randomized 3:1 to receive either V114 or PCV13, followed by PPSV23., Results: Most common solicited adverse events (AEs) following administration of V114 or PCV13 as well as PPSV23 were injection-site pain and fatigue. The proportion of participants with AEs was comparable in both groups. V114 and PCV13 were immunogenic based on opsonophagocytic activity (OPA) geometric mean titers (GMTs) 30 days postvaccination for all serotypes contained in each respective vaccine. OPA GMTs to the 2 unique serotypes in V114 were robust in the V114 group. PPSV23 was immunogenic for all 15 serotypes contained in V114 in both vaccination groups, including 22F and 33F., Conclusions: V114 administered alone or sequentially with PPSV23 is well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, in immunocompetent adults aged 18-49 years with or without certain medical or behavioral risk factors for PD., Clinical Trials Registration: NCT03547167 and EudraCT 2017-004915-38., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible of the current pandemic ongoing all around the world. Since its discovery in 2019, several circulating variants have emerged and some of them are associated with increased infections and death rate. Despite the genetic differences among these variants, vaccines approved for human use have shown a good immunogenic and protective response against them. In Chile, over 70% of the vaccinated population is immunized with CoronaVac, an inactivated SARS-CoV-2 vaccine. The immune response elicited by this vaccine has been described against the first SARS-CoV-2 strain isolated from Wuhan, China and the D614G strain (lineage B). To date, four SARS-CoV-2 variants of concern described have circulated worldwide. Here, we describe the neutralizing capacities of antibodies secreted by volunteers in the Chilean population immunized with CoronaVac against variants of concern Alpha (B.1.1.7), Beta (B.1.351) Gamma (P.1) and Delta (B.617.2)., Methods: Volunteers enrolled in a phase 3 clinical trial were vaccinated with two doses of CoronaVac in 0-14 or 0-28 immunization schedules. Sera samples were used to evaluate the capacity of antibodies induced by the vaccine to block the binding between Receptor Binding Domain (RBD) from variants of concern and the human ACE2 receptor by an in-house ELISA. Further, conventional microneutralization assays were used to test neutralization of SARS-CoV-2 infection. Moreover, interferon-γ-secreting T cells against Spike from variants of concern were evaluated in PBMCs from vaccinated subjects using ELISPOT., Results: CoronaVac promotes the secretion of antibodies able to block the RBD of all the SARS-CoV-2 variants studied. Seropositivity rates of neutralizing antibodies in the population evaluated were over 97% for the lineage B strain, over 80% for Alpha and Gamma variants, over 75% for Delta variant and over 60% for the Beta variant. Geometric means titers of blocking antibodies were reduced when tested against SARS-CoV-2 variants as compared to ancestral strain. We also observed that antibodies from vaccinated subjects were able to neutralize the infection of variants D614G, Alpha, Gamma and Delta in a conventional microneutralization assay. Importantly, after SARS-CoV-2 infection, we observed that the blocking capacity of antibodies from vaccinated volunteers increased up to ten times for all the variants tested. We compared the number of interferon-γ-secreting T cells specific for SARS-CoV-2 Spike WT and variants of concern from vaccinated subjects and we did not detect significant differences., Conclusion: Immunization with CoronaVac in either immunization schedule promotes the secretion of antibodies able to block SARS-CoV-2 variants of concern and partially neutralizes SARS-CoV-2 infection. In addition, it stimulates cellular responses against all variants of concern., Competing Interests: Authors GZ and WM are employed by company SINOVAC Biotech. AS is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. The authors declare this study received the investigational product (placebo and vaccines) from the company SINOVAC Biotech. SINOVAC employees contributed to the conceptualization of the study (clinical protocol and eCRF design) but did not participate in either the analysis or interpretation of the data shown in this manuscript., (Copyright © 2021 Melo-González, Soto, González, Fernández, Duarte, Schultz, Gálvez, Pacheco, Ríos, Vázquez, Rivera-Pérez, Moreno-Tapia, Iturriaga, Vallejos, Berríos-Rojas, Hoppe-Elsholz, Urzúa, Bruneau, Fasce, Mora, Grifoni, Sette, Weiskopf, Zeng, Meng, González-Aramundiz, González, Abarca, Ramírez, Kalergis and Bueno.)

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2 ) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac., Competing Interests: ZG and MW are SINOVAC employees and contributed to the conceptualization of the study (clinical protocol and eCRF design) and did not participate in the analysis or interpretation of the data presented in the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Duarte, Gálvez, Iturriaga, Melo-González, Soto, Schultz, Urzúa, González, Vázquez, Ríos, Berríos-Rojas, Rivera-Pérez, Moreno-Tapia, Pacheco, Vallejos, Hoppe-Elsholz, Navarrete, Rojas, Fasce, Fernández, Mora, Ramírez, Zeng, Meng, González-Aramundiz, González, Abarca, Bueno and Kalergis.)

Background: Chile has one of the highest incidences of COVID-19 infection in the world. Primary care can play a key role in early detection and containment of the disease. There is a lack of information on the clinical profile of patients with suspected COVID-19 in primary care, and controversy on the effectiveness of rapid serologic tests in the diagnosis and surveillance of the disease., Aim: To assess the effectiveness of rapid serologic testing in detection and surveillance of COVID-19 cases in primary care., Design & Setting: A longitudinal study was undertaken, which was based on a non-random sample of 522 participants, including 304 symptomatic patients and 218 high-risk asymptomatic individuals. They were receiving care at four primary health clinics in an underserved area in Santiago, Chile., Method: The participants were systematically assessed and tested for COVID-19 with reverse transcriptase-polymerase chain reaction (RT-PCR) and serology at baseline, and were followed clinically and serologically for 3 weeks., Results: The prevalence rate of RT-PCR confirmed COVID-19 cases were 3.5 times higher in symptomatic patients (27.5%; 95% confidence interval [CI] = 22.1 to 32.8) compared with asymptomatic participants (7.9%; 95% CI = 4.3 to 11.6). Similarly, the immune response was significantly different between both groups. Sensitivity of serologic testing was 57.8% (95% CI = 44.8 to 70.1) during the third week of follow-up and specificity was 98.4% (95% CI = 95.5 to 99.7)., Conclusion: Rapid serologic testing is ineffective for detecting asymptomatic or non-severe cases of COVID-19 at early stages of the disease, but can be of value for surveillance of immunity response in primary care. The clinical profile and immune response of patients with COVID-19 in primary care differs from those in hospital-based populations., (Copyright © 2020, The Authors.)

Background: Respiratory syncytial virus (RSV) is responsible for most respiratory tract infections and hospitalizations in infants and represents a significant economic burden for public health. The development of a safe, effective, and affordable vaccine is a priority for the WHO., Methods: We conducted a double-blinded, escalating-dose phase 1 clinical trial in healthy males aged 18-50 years to evaluate safety, tolerability, and immunogenicity of a recombinant Mycobacterium bovis BCG vaccine expressing the nucleoprotein of RSV (rBCG-N-hRSV). Once inclusion criteria were met, volunteers were enrolled in three cohorts in an open and successive design. Each cohort included six volunteers vaccinated with 5 × 10 3 , 5 × 10 4 , or 1 × 10 5 CFU, as well as two volunteers vaccinated with the full dose of the standard BCG vaccine. This clinical trial (clinicaltrials.gov NCT03213405) was conducted in Santiago, Chile., Findings: The rBCG-N-RSV vaccine was safe, well-tolerated, and no serious adverse events related to the vaccine were recorded. Serum IgG-antibodies directed against Mycobacterium and the N-protein of RSV increased after vaccination, which were capable of neutralizing RSV in vitro . Additionally, all volunteers displayed increased cellular response consisting of IFN-γ and IL-2 production against PPD and the N-protein, starting at day 14 and 30 post-vaccination respectively., Interpretation: The rBCG-N-hRSV vaccine had a good safety profile and induced specific cellular and humoral responses., Funding: This work was supported by Millennium Institute on Immunology and Immunotherapy from Chile (P09/016), FONDECYT 1190830, and FONDEF D11E1098., Competing Interests: Authors KA, ERJ, NMD, YV, JS, NG, JV, CI, MU, AB, JC, VM, PG, JG, SB, and AMK report grants from Millennium Institute on Immunology and Immunotherapy from Chile, grants from Fondo Nacional de Desarrollo Científico y Tecnológico, grants from Fondo de Fomento al Desarrollo Tecnológico, personal fees from Pontificia Universidad Católica de Chile, during the conduct of the study. LV reports personal fees from Pontificia Universidad Católica de Chile, during the conduct of the study ., (© 2020 The Authors.)

Scrub typhus is a potentially fatal rickettsiosis caused by Orientia species intracellular bacteria of the genus Orientia. Although considered to be restricted to the Asia Pacific region, scrub typhus has recently been discovered in southern Chile. We analyzed Orientia gene sequences of 16S rRNA (rrs) and 47-kDa (htrA) from 18 scrub typhus patients from Chile. Sequences were ≥99.7% identical among the samples for both amplified genes. Their diversity was 3.1%-3.5% for rrs and 11.2%-11.8% for htrA compared with O. tsusugamushi and 3.0% for rrs and 14.8% for htrA compared with Candidatus Orientia chuto. Phylogenetic analyses of both genes grouped the specimens from Chile in a different clade from other Orientia species. Our results indicate that Orientia isolates from Chile constitute a novel species, which, until they are cultivated and fully characterized, we propose to designate as Candidatus Orientia chiloensis, after the Chiloé Archipelago where the pathogen was identified.

Background: Scrub typhus is an emerging vector-borne zoonosis, caused by Orientia spp. and transmitted by larvae of trombiculid mites, called chiggers. It mainly occurs within a region of the Asia-Pacific called the tsutsugamushi triangle, where rodents are known as the most relevant hosts for the trombiculid vector. However, the reservoir(s) and vector(s) of the scrub typhus outside Asia-Pacific are unknown. The disease has recently been discovered on and is considered endemic for Chiloé Island in southern Chile. The aim of the present work was to detect and determine the prevalence of chiggers on different rodent species captured in probable sites for the transmission of orientiae responsible for scrub typhus on Chiloé Island in southern Chile and to molecularly examine collected chiggers for the presence of Orientia DNA., Methodology/principal Findings: During the austral summer 2018, rodents were live-trapped in six sites and examined for chigger infestation. All study sites were rural areas on Chiloé Island, previously identified as probable localities where human cases acquired the scrub typhus. During a total of 4,713 trap-nights, 244 rodents of seven species were captured: the most abundant was Abrothrix olivacea. Chiggers were detected on all seven rodent species with a 55% prevalence rate. Chiggers showed low host specificity and varied according to site specific host abundance. Three genera of trombiculids were identified. Herpetacarus was the most abundant genus (93%), prevalent in five of the six sites. Infestation rates showed site specific differences, which were statistically significant using a GLM model with binomial errors. Molecular analyses proved that 21 of 133 (15.8%) mite pools were positive for Orientia species, all of them belonged to the genus Herpetacarus., Conclusions/significance: This study firstly reports the presence of different rodent-associated chigger mites positive for Orientia sp., in a region endemic for scrub typhus in southern Chile. Herpetacarus and two other genera of mites were found with high infestation rates of rodents in sites previously identified as probable exposure of scrub typhus cases. A substantial percentage of mite pools were positive for Orientia DNA, suggesting that chigger mites serve as vectors and reservoirs of this emerging zoonosis in South America., Competing Interests: The authors have declared no competing interests.

Endemic scrub typhus was recently detected on Chiloé Island in southern Chile. We report a series of cases, acquired over a wide geographical range in continental Chile during 2016-2018, demonstrating that this emerging rickettsial infection is also found on the mainland of South America.

Background: Scrub typhus is a potentially life-threatening vector-borne infection caused by Orientia species. It occurs mainly in the Asian-Pacific region, where it causes significant morbidity and mortality. Recently, an endemic focus of scrub typhus has been described in South America, on Chiloé Island in southern Chile. Dogs have been used as sentinel hosts to determine the presence and spatial distribution of various vector-borne infections. Their suitability to gain insight into human exposure to Orientia tsutsugamushi has been suggested in studies from Asia., Methodology: In January 2016, we conducted a cross-sectional study, which included the two main cities on Chiloé Island. Canine blood samples were obtained in households, chosen by double stratified random sampling in urban and by convenience in rural locations. Specimens were tested by ELISA for IgG antibodies against whole-cell antigen preparations from three strains of O. tsutsugamushi. Data were further analyzed for factors associated with seropositivity including spatial clustering., Results: Serum samples from 202 dogs (104 urban, 98 rural) were tested for IgG against O. tsutsugamushi, of which 43 (21.3%) were positive. Seroprevalence rates were higher in rural than in urban settings (p<0.01) and in older compared to younger dogs (p<0.01). Spatial analysis by LISA indicated the presence of four localities of highly grouped cases., Conclusions: The detected seroprevalence supports the endemicity of scrub typhus in southern Chile and suggests a wide exposure of household dogs to the infected, yet unknown vector(s). The spatial data will be used for future research identifying further human cases as well as the local vector(s)/reservoirs for scrub typhus in southern Chile. The study reinforces that dogs are useful sentinels for Orientia spp. in regions of uncertain endemicity and distribution., Competing Interests: The authors have declared that no competing interests exist.

The obligate intracellular bacterium Orientia tsutsugamushi is the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions of O. tsutsugamushi , including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models., (Copyright © 2018 American Society for Microbiology.)

Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections. In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

Background: Coxiella burnetii is an important zoonotic pathogen of global distribution. Still, in most parts of South America including Chile, systematic epidemiological data are lacking. The presented study aims to determine the seroprevalence of Coxiella burnetii antibodies in healthy adults of four different regions in Chile., Methods: A cross-sectional study was performed, which included healthy adults living in rural and urban areas of four cities located in different regions in northern, central, and southern Chile. In urban sectors, households were chosen by double stratified random sampling, while in rural areas convenience sampling was performed. Serum specimens were taken and screened for the presence of IgG antibodies against C. burnetii phase II antigen using a commercial ELISA kit. Positive and indeterminate results were confirmed by a reference laboratory using indirect immunofluorescence assay (IFA)., Results: A total of 1112 individuals were included. Of those, 8 were positive by ELISA, but only one sample was confirmed using IFA. Statistical analysis for population freedom from disease revealed a high probability that C. burnetii was absent in our study population., Conclusion: Our work provides the first epidemiological data on human Q fever in Chile indicating either a very low endemicity or the absence of this pathogen in the studied areas.

One out of three pediatric sepsis deaths in high income countries occur in previously healthy children. Primary immunodeficiencies (PIDs) have been postulated to underlie fulminant sepsis, but this concept remains to be confirmed in clinical practice. Pseudomonas aeruginosa ( P. aeruginosa ) is a common bacterium mostly associated with health care-related infections in immunocompromised individuals. However, in rare cases, it can cause sepsis in previously healthy children. We used exome sequencing and bioinformatic analysis to systematically search for genetic factors underpinning severe P. aeruginosa infection in the pediatric population. We collected blood samples from 11 previously healthy children, with no family history of immunodeficiency, who presented with severe sepsis due to community-acquired P. aeruginosa bacteremia. Genomic DNA was extracted from blood or tissue samples obtained intravitam or postmortem. We obtained high-coverage exome sequencing data and searched for rare loss-of-function variants. After rigorous filtrations, 12 potentially causal variants were identified. Two out of eight (25%) fatal cases were found to carry novel pathogenic variants in PID genes, including BTK and DNMT3B . This study demonstrates that exome sequencing allows to identify rare, deleterious human genetic variants responsible for fulminant sepsis in apparently healthy children. Diagnosing PIDs in such patients is of high relevance to survivors and affected families. We propose that unusually severe and fatal sepsis cases in previously healthy children should be considered for exome/genome sequencing to search for underlying PIDs.

Reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, Boostrix™, is indicated for booster vaccination of children, adolescents and adults. The original prefilled disposable dTpa syringe presentation was recently replaced by another prefilled-syringe presentation with latex-free tip-caps and plunger-stoppers. 671 healthy adolescents aged 10-15 years who had previously received 5 or 6 previous DT(P)/dT(pa) vaccine doses, were randomized (1:1) to receive dTpa booster, injected using the new (dTpa-new) or previous syringe (dTpa-previous) presentations. Immunogenicity was assessed before and 1-month post-booster vaccination; safety/reactogenicity were assessed during 31-days post-vaccination. Non-inferiority of dTpa-new versus dTpa-previous was demonstrated for all antigens (ULs 95% CIs for GMC ratios ranged between 1.03-1.13). 1-month post-booster, immune responses were in similar ranges for all antigens with both syringe presentations. dTpa delivered using either syringe presentation was well-tolerated. These clinical results complement the technical data and support the use of the new syringe presentation to deliver the dTpa vaccine.

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].

Background: Hydatidosis is a zoonotic disease of worldwide distribution caused by Echinococcus granulosus. Our study aimed to determine the prevalence of human and canine echinococcosis as well as the associated risk factors in a rural area of the Limarí province in northern Chile., Methodology/principal Findings: A cross-sectional study was conducted between August and November 2009 using a stratified sampling design in each of the five districts of the province. In the selected villages, up to 10 households were sampled. Serum and fecal samples from an adult family member and a dog were collected from each participating household. Risk factors were assessed by standardized questionnaires. Seroprevalence was assessed using a multi-step approach: an ELISA for screening, IFA, IHA and western blot for confirmation of results, respectively. The prevalence of echinococcal infection in dogs was determined by coproantigen genus specific ELISA. Chi-square, Fisher tests and logistic regressions were used to assess risk factors for human seropositivity and dog copropositivity. A seroprevalence of 2.6% (10/403) and coproprevalence of 28% (26/93) was recorded for humans and dogs respectively. Contact with dogs and dog feces were risk factors for human seropositivity while dog copropositivity was associated with home slaughter of livestock (OR = 3.35; CI 90%: 1.16-6.85) and households de-worming dogs (OR = 2.82; CI 90%: 1.33-8.43)., Conclusions/significance: Echinococcal infection of humans and their dogs is common in Limarí province. Risk factors for human seropositivity were related to contact with domestic dogs and their feces, whereas those for dogs were home slaughter of livestock and the practice of de-worming dogs.

We report a series of 14 patients from 11 kindreds with recessive partial (RP)-interferon (IFN)-γR1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875-2950) and 500 (200-1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-γR1 levels and residual response to IFN-γ. The patients suffered from bacillus Calmette-Guérin-osis (n= 6), environmental mycobacteriosis (n= 6) or tuberculosis (n= 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 ± 9.13 years. Thirteen patients survived until the age of 14.82 ± 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-γR1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases.

Background: Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib)., Methods: This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months., Results: One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses., Conclusions: Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs., Trial Registration: http://www.clinicaltrials.gov NCT00332566.

Background: Respiratory syncytial virus (RSV) is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide. High-risk infants currently receive RSV prophylaxis with palivizumab, a humanized RSV monoclonal antibody (MAb). In preclinical in vitro and in vivo (cotton-rat model) studies, motavizumab, a new RSV MAb, was shown to have greater anti-RSV activity than palivizumab. Motavizumab is currently under review for licensing approval. Since both MAbs may be available concurrently, this study evaluated their safety and tolerability when administered sequentially during the same RSV season., Methods: Between April 2006 and May 2006, 260 high-risk infants were randomly assigned 1:1:1 to receive monthly intramuscular injections: 2 doses of motavizumab followed by 3 doses of palivizumab (M/P); 2 doses of palivizumab followed by 3 doses of motavizumab (P/M); or 5 doses of motavizumab (control). Adverse events (AEs, serious AEs [SAEs]), development of antidrug antibody (ADA), and serum drug trough concentrations were assessed., Results: Most children received all 5 doses (246/260 [94.6%]) and completed the study (241/260 [92.7%]). While overall AE rates were similar (mostly level 1 or 2 in severity), SAEs and level 3 AEs occurred more frequently in the M/P group (SAEs: 22.9% M/P, 8.4% P/M, 11.8% motavizumab only; level 3 AEs: 15.7% M/P, 6.0% P/M, 6.5% motavizumab only). This trend in AE rates occurred before and after switching from motavizumab to palivizumab, suggesting a cause other than the combined regimen. Frequencies of AEs judged by the investigator to be related to study drug were similar among groups. Two deaths occurred on study (both in the M/P group, before palivizumab administration); neither was considered by the site investigator to be related to study drug. Mean serum drug trough concentrations were comparable among groups; ADA detection was infrequent (5.1% or less of any group)., Conclusions: The conclusions drawn from this study are limited by the small sample size per group. However, within this small study, overall AE rates, serum drug trough concentrations, and development of ADA associated with administering motavizumab and palivizumab sequentially to high-risk children appear comparable to administering motavizumab alone during the same RSV season., Trial Registration: clinicaltrials.gov NCT00316264.

Pet diseases may pose risks to human health but are rarely included in surveillance systems. A pilot surveillance system of pet infectious diseases in Santiago, Chile, found that 4 canine and 3 feline diseases accounted for 90.1% and 98.4% of notifications, respectively. Data also suggested association between poverty and pet diseases.

Objectives: To compare the immunogenicity, safety, and interchangeability of two pediatric hepatitis A vaccines, Avaxim 80U-Pediatric and Havrix 720, in Chilean children., Methods: In this randomized trial, 332 hepatitis A virus (HAV) seronegative children from 1 to 15 years of age received two doses of Avaxim, two doses of Havrix, or Havrix followed by Avaxim, 6 months apart. Anti-HAV antibody titers were measured before and 14 days after the first dose of vaccine, and before and 28 days after the second dose of vaccine. Immediate reactions were monitored; reactogenicity was evaluated from parental reports., Results: Seroconversion rates after the first vaccination were 99.4% and 100% for Avaxim and Havrix, respectively. Anti-HAV geometric mean concentrations (GMCs) were 138 mIU/ml for Havrix (95% confidence interval (CI): 120; 159) and 311 mIU/ml for Avaxim (95% CI: 274; 353). GMCs increased to 4008 mIU/ml after two doses of Havrix, 8537 mIU/ml following two doses of Avaxim, and 7144 mIU/ml in children who received Havrix with Avaxim as the second dose. Following the first injection, 36% of subjects given Avaxim and 44% given Havrix reported local reactions; 38% of subjects in the Avaxim group and 40% in the Havrix group reported systemic reactions related to vaccination. Solicited reactions were less frequent after the second dose of Avaxim or Havrix, occurring in 27% to 37% of subjects., Conclusions: No significant difference in seroconversion rates was seen 14 days after a single dose of vaccine. A two-dose schedule with either vaccine or with Havrix/Avaxim provided a strong booster response. Both vaccines were well tolerated and can be recommended for routine vaccination of Chilean children. Avaxim 80 may be used to complete a vaccine schedule begun with Havrix 720.