The added effect of non-pharmaceutical interventions and lifestyle behaviors on vaccine effectiveness against severe COVID-19 in Chile: A matched case-double control study.

BACKGROUND: World Health Organization approved vaccines have demonstrated relatively high protection against moderate to severe COVID-19. Prospective vaccine effectiveness (VE) designs with first-hand data and population-based controls are nevertheless rare. Neighborhood compared to hospitalized controls, may differ in compliance to non-pharmacuetical interventions (NPI) compliance, which may influence VE results in real-world settings. We aimed to determine VE against COVID-19 intensive-care-unit (ICU) admission using hospital and community-matched controls in a prospective design. METHODS: We conducted a multicenter, observational study of matched cases and controls (1:3) in adults ≧18 years of age from May to July 2021. For each case, a hospital control and two community controls were matched by age, gender, and hospital admission date or neighborhood of residence. Conditional logistic regression models were built, including interaction terms between NPIs, lifestyle behaviors, and vaccination status; the model's ß coefficients represent the added effect these terms had on COVID-19 VE. RESULTS: Cases and controls differed in several factors including education level, obesity prevalence, and behaviors such as compliance with routine vaccinations, use of facemasks, and routine handwashing. VE was 98·2% for full primary vaccination and 85·6% for partial vaccination when compared to community controls, and somewhat lower, albeit not significantly, compared to hospital controls. A significant added effect to vaccination in reducing COVID-19 ICU admission was regular facemask use and VE was higher among individuals non-compliant with the national vaccine program, and/or tonroutine medical visits during the prior year. CONCLUSION: VE against COVID-19 ICU admission in this stringent prospective case-double control study reached 98% two weeks after full primary vaccination, confirming the high effectiveness provided by earlier studies. Face mask use and hand washing were independent protective factors, the former adding additional benefit to VE. VE was significantly higher in subjects with increased risk behaviors.

Effect of Helicobacter pylori eradication therapy on clinical and laboratory biomarkers associated with gastric damage in healthy school-aged children: A randomized non-blinded trial.

OBJECTIVES: Helicobacter pylori (H. pylori) is the primary cause of gastric cancer and eradication in healthy adults has proven effective in decreasing cancer incidence. H. pylori is acquired largely in early childhood, however, the benefits of eradication in children are controversial. We aimed to determine the effect of H. pylori eradication on clinical and laboratory markers associated with gastric damage in apparently healthy school-aged children. METHODS: This was a pilot non-blinded trial including 61 children persistently infected with H. pylori who were randomized to eradication/no treatment and followed for at least 12 months, evaluating clinical and blood markers (Pepsinogen I (PGI) and II (PGII) determined by ELISA) associated with gastric damage. The treatment consisted of a sequential scheme including 7 days of omeprazole + amoxicillin followed by 7 days of omeprazole + clarithromycin + metronidazole; adherence and tolerance were surveyed. Eradication rates were assessed by stool antigen detection or urea breath test 1 month following treatment every 4 months thereafter to detect reinfection. RESULTS: Eradication occurred in 30/31 treated children (median age: 8.8, range: 7.9-10.8) and in 0/30 non-treated controls (median age: 8.6, range: 7.9-11) (p < .001). Treatment was associated with mild transient symptoms (altered taste, nocturnal upper abdominal pain, nausea, and diarrhea). Baseline frequency of symptoms was low and eradication did not change symptoms compared to controls. PGI, PGII, and anti-H. pylori seropositivity were similar in both groups at baseline and significantly decreased only in eradicated patients; PGI (92.5 vs. 74.4, p < .001), PGII (15.2 vs. 8.9, p < .001) levels, and frequency of anti-H. pylori seropositivity (100 vs. 68%, p < .001) respectively. Four eradicated children (13%) were reinfected during follow-up. CONCLUSIONS: H. pylori eradication therapy in apparently asymptomatic school-aged children was well tolerated and associated with decreased serum PGI and PGII levels. Future studies should expand on the middle-long-term effect of early H. pylori eradication, especially on preventing gastric cancer.

Norovirus vaccines under development.

Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis, including both outbreaks and endemic infections. The development of preventive strategies, including vaccines, for the most susceptible groups (children <5years of age, the elderly and individuals suffering crowding, such as military personnel and travelers) is desirable. However, NoV vaccine development has faced many difficulties, including genetic/antigenic diversity, limited knowledge on NoV immunology and viral cycle, lack of a permissive cell line for cultivation and lack of a widely available and successful animal model. Vaccine candidates rely on inoculation of virus-like particles (VLPs) formed by the main capsid protein VP1, subviral particles made from the protruding domain of VP1 (P-particles) or viral vectors with a NoV capsid gene insert produced by bioengineering technologies. Polivalent vaccines including multiple NoV genotypes and/or other viruses acquired by the enteric route have been developed. A VLP vaccine candidate has reached phase II clinical trials and several others are in pre-clinical stages of development. In this article we discuss the main challenges facing the development of a NoV vaccine and the current status of prevailing candidates.

Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial.

BACKGROUND: Replacement of the trivalent oral poliovirus vaccine (tOPV) with bivalent types 1 and 3 oral poliovirus vaccine (bOPV) and global introduction of inactivated poliovirus vaccine (IPV) are major steps in the polio endgame strategy. In this study, we assessed humoral and intestinal immunity in Latin American infants after three doses of bOPV combined with zero, one, or two doses of IPV. METHODS: This open-label randomised controlled multicentre trial was part of a larger study. 6-week-old full-term infants due for their first polio vaccinations, who were healthy on physical examination, with no obvious medical conditions and no known chronic medical disorders, were enrolled from four investigational sites in Colombia, Dominican Republic, Guatemala, and Panama. The infants were randomly assigned by permuted block randomisation (through the use of a computer-generated list, block size 36) to nine groups, of which five will be discussed in this report. These five groups were randomly assigned 1:1:1:1 to four permutations of schedule: groups 1 and 2 (control groups) received bOPV at 6, 10, and 14 weeks; group 3 (also a control group, which did not count as a permutation) received tOPV at 6, 10, and 14 weeks; group 4 received bOPV plus one dose of IPV at 14 weeks; and group 5 received bOPV plus two doses of IPV at 14 and 36 weeks. Infants in all groups were challenged with monovalent type 2 vaccine (mOPV2) at 18 weeks (groups 1, 3, and 4) or 40 weeks (groups 2 and 5). The primary objective was to assess the superiority of bOPV-IPV schedules over bOPV alone, as assessed by the primary endpoints of humoral immunity (neutralising antibodies-ie, seroconversion) to all three serotypes and intestinal immunity (faecal viral shedding post-challenge) to serotype 2, analysed in the per-protocol population. Serious and medically important adverse events were monitored for up to 6 months after the study vaccination. This study is registered with ClinicalTrials.gov, number NCT01831050, and has been completed. FINDINGS: Between May 20, 2013, and Aug 15, 2013, 940 eligible infants were enrolled and randomly assigned to the five treatment groups (210 to group 1, 210 to group 2, 100 to group 3, 210 to group 4, and 210 to group 5). One infant in group 1 was not vaccinated because their parents withdrew consent after enrolment and randomisation, so 939 infants actually received the vaccinations. Three doses of bOPV or tOPV elicited type 1 and 3 seroconversion rates of at least 97·7%. Type 2 seroconversion occurred in 19 of 198 infants (9·6%, 95% CI 6·2-14·5) in the bOPV-only groups, 86 of 88 (97·7%, 92·1-99·4) in the tOPV-only group (p<0·0001 vs bOPV-only), and 156 of 194 (80·4%, 74·3-85·4) infants in the bOPV-one dose of IPV group (p<0·0001 vs bOPV-only). A further 20 of 193 (10%) infants in the latter group seroconverted 1 week after mOPV2 challenge, resulting in around 98% of infants being seropositive against type 2. After a bOPV-two IPV schedule, all 193 infants (100%, 98·0-100; p<0·0001 vs bOPV-only) seroconverted to type 2. IPV induced small but significant decreases in a composite serotype 2 viral shedding index after mOPV2 challenge. 21 serious adverse events were reported in 20 patients during the study, including two that were judged to be possibly related to the vaccines. Most of the serious adverse events (18 [86%] of 21) and 24 (80%) of the 30 important medical events reported were infections and infestations. No deaths occurred during the study. INTERPRETATION: bOPV provided humoral protection similar to tOPV against polio serotypes 1 and 3. After one or two IPV doses in addition to bOPV, 80% and 100% of infants seroconverted, respectively, and the vaccination induced a degree of intestinal immunity against type 2 poliovirus. FUNDING: Bill & Melinda Gates Foundation.

Management of acute infectious diarrhea for children living in resource-limited settings.

Acute infectious gastroenteritis continues to be a leading cause of morbidity and mortality in children below 5 years of age, with the majority of deaths concentrated in 35 'low income' countries. In these countries the under five years of age mortality rates reach 100 per 1000 live births, of which a significant proportion are associated with acute diarrhea. Rotavirus, cryptosporidium, Shigella spp and enterotoxigenic Escherichia coli are the main pathogens causing disease in these settings, although other bacteria and parasites can cause moderate to severe disease in different regions and situations. Treatment of children in these setting should be focused on appropriate rehydration, early hospitalization of severely malnourished children, zinc supplementation, and in specific situations, antimicrobials should be considered. The rationale for antimicrobial use should be based on the potential benefits based on published literature and the opportunity for use. This review provides a pathogen-specific update on the potential benefits of antimicrobials and suggests an empirical management approach for children suffering an acute watery or bloody diarrhea in a resource-limited region.

[Outbreaks of acute gastroenteritis in Antofagasta Region, Chile 2010]. / Brote de gastroenteritis aguda en la Región de Antofagasta,Chile: 2010.

Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.

Brote de gastroenteritis aguda en la Región de Antofagasta,Chile: 2010 / Outbreaks of acute gastroenteritis in Antofagasta Region: Chile 2010

Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.

Antecedentes: Los brotes por gastroenteritis aguda constituyen un problema de salud pública. Se conoce al norovirus como la causa más común (50%). En Chile, la vigilancia de estos eventos, se establece mediante la notificación inmediata. Objetivo: Investigar y caracterizar el brote de gastroenteritis aguda ocurrido en la Región de Antofagasta, durante los meses de marzo y abril de 2010. Método: Se efectuó un estudio observacional descriptivo para realizar la investigación de brote. Se incluyó a residentes de la región que cumplían con la definición de caso. Se solicitó muestras de deposición, encuesta epidemiológica y muestras ambientales. Resultados: Se estimó que el brote comenzó el 8 de marzo de 2010 y duró hasta el 28 de abril del mismo año; se notificaron 31. 036 casos (tasa 54 por 1.000 habitantes). El grupo de 25 y 44 años de edad fue el más afectado y la diarrea fue el síntoma predominante (97% de los casos). Se determinó la presencia de norovirus genogrupo II en muestras clínicas y ambientales. Conclusiones: El brote se originó por el consumo crudo de hortalizas que provenían del sector La Chimba, las que fueron regadas y contaminadas con agua servida tratada que contenía baja concentración de cloro libre residual y posteriormente se propagó por transmisión persona-persona, en un ambiente sanitario deficiente.

[Reflections and feelings from a team of volunteers from the Ministry of Health and the Chilean Medical Association, after the recent earthquake]. / Reflexiones y sentimientos desde un equipo de voluntarios del Ministerio de Salud y el Colegio Médico de Chile, después del terremoto reciente.

The experience of a group of 9 doctors and 6 nurses, most of them younger than 30 years of age, whom were part of the several volunteer groups directed towards the most damaged earthquake regions, is described. The team had to overcome a number of intense personal emotions related with the magnitude of the destruction, especially in the "adobe"-constructed houses and villages, in order to provide useful medical support. Moving out of the hospital setting, reaching out to the community in schools and emergency posts proved to be important in rural communities. An appropriate coordination of the volunteer groups, with the simultaneous action of municipal and state health authorities, together with well-guided leadership, was critical for an effective response in the larger city of Talcahuano /Hualpén. Within the second week of the aftermath, acute respiratory and intestinal infections were the most common medical complaints together with intense -in many cases severe- emotional distress associated mostly with fear to after shakes ("replicas"), tsunami, and social unrest. The severe earthquake that struck Chile has left many lessons for the future that will need to be analyzed seriously and with the conviction that effective and timely prevention of catastrophic aftermath consequences, although costly, must be a key element of the country's development plan. More importantly, the hundreds if not thousands of volunteers from a variety of health related professions that were moved by the scenes of suffering, and whom responded to individual or group initiatives, allow to foresee that the nation has the moral stamina required to overcome the tragedy and become a better society.

Reflexiones y sentimientos desde un equipo de voluntarios del Ministerio de Salud y el Colegio Médico de Chile, después del terremoto reciente / Reflections and feelings from a team of volunteers from the Ministry of Health and the Chilean Medical Association, after the recent earthquake

The experience of a group of 9 doctors and 6 nurses, most of them younger than 30years of age, whom were part of the several volunteer groups directed towards the most damaged earthquake regions, is described. The team had to overcome a number of intense personal emotions related with the magnitude of the destruction, especially in the "adobe"-constructed houses and villages, in order to provide useful medical support. Moving out of the hospital setting, reaching out to the community in schools and emergency posts proved to be important in rural communities. An appropriate coordination of the volunteer groups, with the simultaneous action of municipal and state health authorities, together with well-guided leadership, was critical for an effective response in the larger city of Talcahuano /Hualpén. Within the second week of the aftermath, acute respiratory and intestinal infections were the most common medical complaints together with intense -in many cases severe- emotional distress associated mostly with fear to after shakes ("replicas"), tsunami, and social unrest. The severe earthquake that struck Chile has left many lessons for the future that will need to be analyzed seriously and with the conviction that effective and timely prevention of catastrophic aftermath consequences, although costly, must be a key element of the country's development plan. More importantly, the hundreds if not thousands of volunteers from a variety of health related professions that were moved by the scenes of suffering, and whom responded to individual or group initiatives, allow to foresee that the nation has the moral stamina required to overcome the tragedy and become a better society.

Bocavirus humano: Estudios en la literatura médica y en Chile / Human bocavirus: Studies in the literature and in Chile

The human bocavirus (HBoV), virus of the Parvoviridae family, discovered by molecular methods in 2005,has been reported in respiratory samples, stool, urine and blood, both in children and adults. Prevalence ratesrange from 0.8% in fecal samples of individuals with acute diarrhea, up to 19% in respiratory samples and blood.HBoV has been detected in up to 43% of nasopharyngeal samples in asymptomatic children. In Chile, HBoV wasdetected in 24.2% of nasopharyngeal swabs in children under 5 years of age with respiratory symptoms of which74% had coinfection with other viruses. In asymptomatic children under 5 years of age, 37.5% of NP sampleswere positive for HBoV. We discuss the role of HBoV as a causal agent of respiratory and/or enteric disease inlight of the high rates of coinfection and asymptomatic infections.

Declaración del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología respecto a la vacuna anti-virus papiloma humano: septiembre 2008 / Human papillomavirus vaccine: statement of the Consultive Committee of Immunizations on behalf of The Chilean Infectious Diseases Society: September 2008

The article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases in the world and in Chile and the scientific information of the licensed HPV vaccines: Gardasil® and Cervarix®. Considering the available information, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases, summarizes its conclusions and makes recommendations for vaccination against HPV in Chile.

El artículo revisa brevemente la epidemiología de las infecciones por virus papiloma humano (VPH) y las enfermedades asociadas, tanto en el mundo como en Chile y la información científica de las vacunas contra VPH licenciadas: Gardasil® y Cervarix®. Considerando la información disponible, el Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología, resume sus conclusiones y hace sus recomendaciones para la vacunación contra VPH en Chile.

Resultados de la vigilancia centinela de gastroenteritis por rotavirus en Chile / Sentry surveillance study of rotavirus gastroenteritis in Chile

A sentinel-based outpatient and inpatient surveillance for rotavirus infection has been implemented in Chile. Aim: Update the impact of rotavirus infections in Chile. Methods: Ambulatory surveillance is performed in 14 centers from 8 Regions and hospital-based surveillance in 8 hospitals from three Regions (V, VIII and Metropolitan). Results: In 2007, 339 stool samples that represented 9.3 percent of all outpatient cases were studied of which 15 percent were rotavirus positive. A total of 2.074 children younger than 5 years of age were hospitalized representing 9 percent of all hospitalizations for this age group. Rotavirus was detected in 13.6 percent of these cases. Conclusions: In the current epidemiological situation, rotavirus surveillance needs to be sustained with increased efforts to detect cases in order to avoid underreporting. Serotype/genotype surveillance of rotavirus strains needs to be included in the near future.

En Chile, se realiza la vigilancia de gastroenteritis causadas por rotavirus en niños bajo 5 años a través de centros centinelas ambulatorios y hospitalarios. Objetivo: Conocer la epidemiología de las diarreas por rotavirus y evaluar la carga de morbi-mortalidad. Método: La vigilancia ambulatoria se desarrolla en 14 centros de 8 regiones y la vigilancia hospitalaria se lleva a cabo en 8 hospitales pediátricos de las regiones Vª, VIIIªy RM. Resultados: En 2007, 9,3 por ciento de las consultas por diarrea fue estudiada (339), detectándose rotavirus en 15 por ciento de ellas. Se hospitalizaron por diarrea, 2.074 casos, 9 por ciento del total de las hospitalizaciones en este grupo etario. De estas, 13,6 por ciento fueron por rotavirus. Conclusiones: Dada la situación epidemiológica actual, es importante mantener la vigilancia, ampliar la pesquisa de los casos, aplicar el protocolo de vigilancia establecido y determinar el serotipo/genotipo circulante en el país.

Virus papiloma humano y cáncer cérvico-uterino: [editorial] / Papillomavirus and cervical cancer in Chile: [editorial]

Molecular, clinical and epidemiolagical studies have established beyond doubt that human papiloma viruses (HPV) cause cervical cancer. The virus is also associated with genital warts and other less common cancers in oropharynx, vulva, vagina and penis. Worldwide, VPH genotypes 16 and 18 are the most common high risk genotypes, detected in near 70 percent of women with cervical cáncer. The discovery of a cause-effect relationship between several carcinogenic microorganisms and cancer open avenues for new diagnostic, treatment and prevention strategies. In this issue of Revista Médica de Chile, two papers on HPV are presented. Guzman and colleagues demonstrate that HPV can be detected in 66 percent to 77 percent of healthy male adolescents by polymerase chain reaction and that positivity depends on the site of the penis that is sampled. These results support the role of male to female transmission of high risk HPVs in Chile and should lead to even more active educational campaigns. The second paper provides recommendations for HPV vaccine use in Chile, generated by the Immunization Advisory Committee of the Chilean Infectious Disease Society. To issue these recommendations, the Committee analyzes the epidemiological information available on HPV infection and cervical cancer in Chile, vaccine safety and effectiveness data, and describes cost-effectiveness studies. Taking into account that universal vaccination is controversial the Committee favors vaccine use in Chile and it's incorporation into a national program. However, there is an indication that the country requires the implementation of an integrated surveillance approach including cross matching of data obtained from HPV genotype surveillance, monitoring of vaccination coverage, and surveillance of cervical cáncer The final decision of universal vaccine use in Chile should be based on a through analysis of information.

Declaración del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología respecto a la vacuna antivirus papiloma humano: Septiembre 2008 / Human papillomavirus vaccine: Statement of the Advisory Committee of Immunizations on Behalf of the Chilean Infectious Diseases Society: September 2008

This article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases globally and in Chile, and the scientific ínformatíon of the licensed HPV vaccines: Gardasil® and Cervarix®. Considering the available information, the Advisory Committee on Immunizations of the Chilean Society of Infectious Diseases recommends vaccination of teenage girls, ideally before initiating sexual actívíty, Le. approximately at the age of 12 to 13 years and vaccination of women of any age if they have not started sexual activity. If women are vaccinated after initiating sexual activity, they should be informed of the lower efficacy of immunization if HPV infection has occurred. Education on responsible sexuality and sexually transmitted diseases should be maintained as a priority. Vaccination should be highly considered for inclusion in the National Immunization Program.

[Human papillomavirus vaccine. Statement of the Consultive Committee of Immunizations on behalf of the Chilean Infectious Diseases Society. September 2008]. / Declaración del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología respecto a la vacuna anti-virus papiloma humano. Septiembre 2008.

The article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases in the world and in Chile and the scientific information of the licensed HPV vaccines: Gardasil and Cervarix. Considering the available information, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases, summarizes its conclusions and makes recommendations for vaccination against HPV in Chile.

[Sentry surveillance study of rotavirus gastroenteritis in Chile]. / Resultados de la vigilancia centinela de gastroenteritis por rotavirus en Chile.

UNLABELLED: A sentinel-based outpatient and inpatient surveillance for rotavirus infection has been implemented in Chile. AIM: Update the impact of rotavirus infections in Chile. METHODS: Ambulatory surveillance is performed in 14 centers from 8 Regions and hospital-based surveillance in 8 hospitals from three Regions (V, VIII and Metropolitan). RESULTS: In 2007, 339 stool samples that represented 9.3% of all outpatient cases were studied of which 15% were rotavirus positive. A total of 2.074 children younger than 5 years of age were hospitalized representing 9% of all hospitalizations for this age group. Rotavirus was detected in 13.6% of these cases. CONCLUSIONS: In the current epidemiological situation, rotavirus surveillance needs to be sustained with increased efforts to detect cases in order to avoid underreporting. Serotype/genotype surveillance of rotavirus strains needs to be included in the near future.