A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19).

BACKGROUND: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. METHODS: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 µg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. DISCUSSION: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.

Fatal Yellow Fever in Travelers to Brazil, 2018.

Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of São Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espírito Santo, São Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile.

Serological diagnosis of Zika virus is challenging due to high cross-reactivity of Zika virus with other flavivirus antibodies. Recently, a Zika NS1-based enzyme-linked immunosorbent assay (ELISA) was developed and shown to be highly specific for Zika antibody detection; however, sensitivity was evaluated for only a small number of confirmed Zika-infected patients. In this study, we measured the sensitivity and kinetics of Zika IgM and IgG antibodies using the Zika NS1-based ELISA in 105 samples from 63 returning travelers infected with Zika virus (proven by PCR or neutralization assay) from Israel, Czech Republic, Italy, Belgium, Germany, and Chile. Zika virus IgM was detected from 2 to 42 days post-symptom onset (PSO) with an overall sensitivity of 79% in the first month and 68% until 2 months PSO, while IgG antibodies were detected from 5 days to 3 years PSO with 79% sensitivity. Interestingly, significant differences in IgM sensitivity and IgM detection period were observed between Israeli and European/Chilean Zika-infected travelers, adding to the complexity of Zika infection diagnosis and suggesting that other diagnostic methods should be complemented to reduce false-negative results.

[Recommendations for Chilean travelers to the FIFA World Cup 2014 in Brazil]. / Recomendaciones para viajeros chilenos a la Copa Mundial de la FIFA 2014 en Brasil.

This article provides a checklist of precautions and vaccines for Chilean travelers attending the FIFA World Cup 2014 in Brazil. It aims to help physicians to prepare visitors of this mass gathering and summarizes useful hints to avoid infectious diseases considering the circumstances and availabilities in Chile.

Intestinal protozoa in returning travellers: a GeoSentinel analysis from 2007 to 2019.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

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 2nd 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.

Interferon ß-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial.

Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNß-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 µg subcutaneous pegylated IFNß-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNß-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNß-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNß-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNß-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.

Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile.

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.

[Salmonellosis outbreaks and the size and role of the Chilean State]. / Brotes de salmonelosis y el tamaño y rol del Estado en Chile.

UNLABELLED: During year 2011 two outbreaks of Salmonella infection captured media attention in the Metropolitan Area (MA) in Chile: one of typhoid fever associated to Salmonella serotype Typhi, and the other, of gastroenteritis related to Salmonella serotype Enteritidis, both with decreasing or stable rates in the previous years. The aim of this work is to analyze probable causes of their reemergence. METHODS: Several government websites were searched looking for epidemiological data. RESULTS: Typhoid fever rates have declined to current values of 1 case per 100.000 habitants, a decreased associated to improvements in the human development index. The typhoid outbreak was associated to a predominant clone within the MA. The only risk factor identified was consumption of raw vegetables acquired in open fairs, but without identifying a common source. Despite improvements in disease notification and molecular epidemiology capabilities, this outbreak is coincidental with a reduced number of food inspection visits in the MA, probably explained by the limited personnel available for this task. In the case of Salmonella Enteritidis, rates have increased twice since 1998 (5.3 to 10.7 per 100.000 habitants) with an important increase in the number of outbreaks linked to this agent (7 to 31 annual outbreaks) since year 2005. Persistence of this problem is probably associated to the low surveillance of poultry farms made by the Chilean state, to the absence of a cold chain during collection, distribution and selling of eggs, and to the lack of an educational program directed to the population. The recent regulation that bans home-made mayonnaise in restaurant or fast food stores is an important advance that requires further evaluation. CONCLUSIONS: The persistence and reemergence of different kind of Salmonellosis in Chile suggests chronic problems on the size and role of the Chilean state regarding food safety.

Clinical and epidemiological characteristics of SARS-CoV-2 virus in ambulatory children under 2 years old.

Background: SARS-CoV-2 is an emerging virus that has mainly affected adults; hence, most clinical information has been derived from that population. Most pediatric cases are mild and with nonspecific symptoms requiring outpatient management. Children are a major source of spread for most traditional respiratory viruses. Their role in SARS-CoV-2 transmission was thought to be relevant. Children under the age of two comprise a group that is more susceptible to infection since vaccines have not been approved for them until recently. The knowledge of clinical manifestation of COVID-19 in young children is scarce. Objectives: To describe the clinical, epidemiological, and demographic characteristics of children under 2 years old with confirmed COVID-19, who did not require hospitalization. Methods: This descriptive study was performed from May, 2020 to June, 2021. Children ages 0-2 years with COVID-19, confirmed by transcriptase-polymerase chain reaction assay that were performed in laboratories of the Red de Salud UC CHRISTUS Health Network, were selected to be contacted. If the parents accepted participating and their children were not hospitalized, a survey was sent to the patients' caregivers. Results: Of the 242 cases, 159 caregivers answered the survey (65.7%). The median age of the subjects was 14 months, and 53.5% were males. Fifty percent had comorbidities, of which one third corresponded to atopy. Ninety eight percent were secondary cases. Most of them were infected within their households (81%). The most frequent sources were their parents, followed by their grandparents. The most common symptom was fever (78%) followed by irritability (67.3%), rhinorrhea (66%), and fatigue (64.8%). Infants less than 6 months old more often presented with conjunctival congestion and less loss of appetite compared to older children (p < 0.05). Conclusions: This study provides valuable insights regarding COVID-19 in ambulatory young children. Most cases of SARS-CoV-2 infection in children under 2 years old do not require hospitalization. There was a slight male predominance, and the majority had been infected within their households. SARS-CoV-2 infection should be suspected in children under 2 years old presenting with fever, irritability, fatigue, and rhinorrhea. Children with positive household contacts and fever should also be tested for COVID-19.

Age as risk factor for death from pandemic (H1N1) 2009, Chile.

Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons >60 years of age at risk for severe disease and death independent of concurrent conditions. Age >60 years was the major risk factor for death from pandemic (H1N1) 2009.

[Source of infection in young infants hospitalized with Bordetella pertussis]. / Fuente de infección de Bordetella pertussis en lactantes hospitalizados por coqueluche.

BACKGROUND: Despite pertussis vaccination, very young infants have the highest rates of morbidity and mortality caused by the microorganism. AIM: To determine the source of Pertussis infection in infants aged six months or less in Chile. MATERIAL AND METHODS: Twenty six household contacts of 10 young infants hospitalized with confirmed Pertussis were studied for the presence of Bordetella Pertussis by polymerase chain reaction (PCR). Clinical and demographic data were analyzed. RESULTS: Respiratory symptoms were present in 20 (77%) contacts, being cough the most common. Pertussis cases were identified in every household and in 18 (72%) of the household members. four members with B.pertussis were asymptomatic. Source of infection was identified in 80% (8/10) of the infant cases with ages ranging from 6 to 62 years. Half of primary cases had positive PCR and their cough duration was significantly shorter compared to primary cases with negative PCR. CONCLUSIONS: B. pertussis transmission to young infants occurred mainly within the household where adults are generally the source of the infection. Risk factors for infant infection are the same as in developed countries. Therefore, the same strategies, such as routine vaccination in adolescents and adults or cocoon strategy, will help to prevent this disease in infants.

Emergent Pneumonia in Children.

In recent decades there have been multiple pathogens, viruses and bacteria, which have emerged as causal agents of pneumonia affecting adults, albeit less frequently, to children. For the purposes of this article we have classified emerging pathogens as follows: True emerging, to pathogens identified for the very first time affecting human population (SARS-CoV-1, SARS-CoV-2, MERS-CoV, avian influenza, and hantavirus); Re-emerging, to known pathogens which circulation was controlled once, but they have reappeared (measles, tuberculosis, antimicrobial resistant bacteria such as CA-MRSA, Mycoplasma pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and new serotypes of post-vaccine pneumococcal); and finally, those that we have called old known with new presentations, including common pathogens that, in particular condition, have changed their form of presentation (rhinovirus, and non-SARS coronavirus). We will review for each of them their epidemiology, forms of presentation, therapy, and prognosis in children compared to the adult with the aim of being able to recognize them to establish appropriate therapy, prognostics, and effective control measures.

[Temporal association between the circulation of respiratory viruses and hospitalizations due to Kawasaki disease]. / Asociación temporal entre la circulación de virus respiratorios y hospitalizaciones por enfermedad de Kawasaki.

BACKGROUND: The etiology of Kawasaki disease (KD) is unknown. It is believed that viral infections could trigger the disease in susceptible patients. AIM: To study the temporal association between the circulation of respiratory viruses and KD hospitalizations in the Metropolitan Region (MR), Chile, between 2010-2017. METHODS: Ecologic study consisting of a review of KD cases in children under 18 years of age based on hospital discharges. The circulation of respiratory viruses was analyzed using the report of the metropolitan surveillance network. Moving averages for KD (MAKD) and respiratory viruses (MARV) were used. RESULTS: 14,902 cases of respiratory virus infections were recorded between 2010-2017. A direct correlation was found between MARV-respiratory syncytial virus (RSV) of one month and year and MAKD of the subsequent month (correlation coefficient (ρ) = +0.441; p < 0.001). A similar association was found for MARV-influenza A (FLU A) (ρ = + 0.362; p < 0.001). MARV-influenza B (FLU B) and MARV-metapneumovirus (MPV) had direct correlations with MAKD (ρ = +0.443; p < 0.001 and ρ = +0.412; p < 0.001, respectively), being FLU B contemporary in month and year with KD, and MPV presenting a one-month lag. CONCLUSION: There is a direct temporal correlation between RSV, FLU A, FLU B and MPV circulation and KD in children from RM, Chile.

Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries.

Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces cross-reactive antibodies against other flaviruses. These attributes complicate the ability to differentially diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirus-specific peptides on 339 samples that were previously collected from 6 countries. Overall, we found that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015-2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions. These findings can contribute to ongoing serological methods development and can be adapted for use in future studies.

[Interactive, semi-automatized and open source computational model applied to respiratory viruses surveillance]. / Modelo computacional interactivo, semi-automatizado y de código abierto aplicado a la vigilancia de virus respiratorios.

Acute respiratory infections (ARI) are an important cause of morbidity and mortality worldwide, affecting mainly children and the elderly. They are associated with a high economic burden, increased number of medical visits and hospitalizations. The surveillance of the circulation of respiratory viruses can reduce the health care associated costs, and to optimize the health response. A platform based on R and its package Shiny was designed, to create an interactive and friendly web interface for gathering, analysis and publication of the data. The data from the Chilean metropolitan respiratory viruses surveillance network, available since 2006, was uploaded into the platform. Using this platform, the researcher spends less than 1 minute to upload the data, and the analysis and publication is immediate, available to be seen by any user with a device connected to Internet, who can choose the variables to be displayed. With a very low cost, in a short time, and using the R programming language, it was possible to create a simple, and interactive platform, considerably decreasing the upload and analysis time, and increasing the impact and availability of this surveillance.

[Bartonella henselae with atypical infection and neuroretinitis in a pediatric unit: report of three cases]. / Infección atípica y neurorretinitis por Bartonella henselae en una unidad de hospitalización pediátrica: comunicación de tres casos.

Bartonella henselae is cat scratch disease's etiological agent, which is considered an endemic infection in Chile. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal or atypical manifestations: hepatosplenic, ocular or musculoskeletal involvement, among others. We present three cases of atypical cat scratch disease with ocular compromise, as neurorretinitis. This review highlights the importance of the active search for ocular complications in patients with disseminated cat scratch disease, leading to possible change in treatment and prognosis of the disease.

Immunogenicity, safety, and interchangeability of two inactivated hepatitis A vaccines in Chilean children.

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.