Miguel O'Ryan G

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.

Situación epidemiológica de las enfermedades transmitidas por alimentos en Santiago de Chile: período 1999-2000

Background: Foodborne diseases are becoming an important cause of morbidity in Chile. In the Metropolitan Region of Chile, the Environmental Health Service started a surveillance program for foodborne diseases in 1994. In 2000, this program was complemented with an etiologic study of individuals involved in outbreaks. Aim: To report the incidence of foodborne outbreaks in the Metropolitan Region of Chile and its causative agents. Results: One hundred ninety outbreaks of foodborne diseases were reported in 1999 and 260 in 2000. The Southern Metropolitan health service had the higher incidence rates (7.5 in 1999 and 8.2 in 2000). The mean attack rates were 25% in both periods, affecting 1248 individuals in 1999 and 1774 in 2000. In 18% of outbreaks, a pathogen was identified; the most frequent agents were Salmonella Spp, Staphylococcus aureus and Shigella. In 15% of subjects, the cause was histamine or chemical agents. In the rest of the cases, the cause was not identified. The foods with higher risk of causing foodborne diseases were hot prepared dishes, home made goat cheese and meats. Conclusions: The incidence rates of foodborne disease in Metropolitan Area of Chile are high and maybe underestimate, only in a low rate of outbreaks was possible to have samples for etiologic studies. For a better understanding of this problem, timely notification of foodborne diseases must be encouraged and educational campaigns about the proper manipulation of food items must be implemented (Rev Med Chile 2002; 130: 495-501)

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.

Perfil epidemiológico y clínico de la invaginación intestinal en lactantes de la Región Metropolitana

Background. Intussusception (IS) is a potentially severe disease that affects an undetermined number of Chilean infants. The withdrawal of a rotavirus vaccine in 1999 due to its association with IS, highlighted the need for updated information on IS worldwide including Chile, before introduction of new vaccines. Aim: To estimate the incidence and to describe the epidemiology and clinical presentation of IS in the Metropolitan Area of Chile. Material and methods. IS cases occurring between 1996 and 2001 in the seven public pediatric hospitals and in six private clinics (during 2000 and 2001) were identified. Incidence rates were calculated using updated population estimates. A systematic review of the medical charts of IS cases occurring in the public hospitals for 2000-2001 was performed. Results. IS incidence rates for the Public Sector ranged from 32 to 39 per 100.000 children < 2 years of age. These figures did not vary significantly among the different Health Care Services, nor after inclusion of the private clinics. IS was more common in males (66%) and infants younger than 12 months (83%), with 67% of cases occurring between 3 and 8 months of age. The most common presenting symptoms were abdominal pain (90%), vomiting (86%), and rectal bleeding (75%). Ileocolic IS predominated (83%) and surgical correction was the preferred treatment (81%). No death occurred in this series. Conclusions: IS incidence rates were intermediate compared to other series, stable over time, and similar between the public and private sector. Clinical characteristics were similar to those previously reported with a disproportionately high use of surgical correction over enema, currently considered the preferred treatment option. (Rev Med Chile 2004; 132: 565-72) (Key-words: Infant welfare; Intussusception; Rotavirus)

Declaración del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología respecto a la vacuna antivirus papiloma humano: Septiembre 2008

Resumen El articulo revisa brevemente la epidemiologia delas infecciones por virus papiloma humano (VPH) ylas enfermedades asociadas, tanto en el mundo comoen Chile y la informacion cientifica de las vacunas Referencias 1.- Parkin D M, Bray F. Chapter 2: The burdenof VPH-related cancers. In: Bosch FX, CuzikJ, Schiller JT, Garnett GP, Micheus A,Franco EL and Wright TC, editors. VPHvaccines and screening in the prevention ofcervical cancer. Vaccine 2006; 24 Suppl 3;S3/11-25.2.- Munoz N, Castellsague X, Berrington A,Gissmann L. Chapter 1: VPH in theetiology of human cancer. In: Bosch FX,Cuzik J, Schiller JT, Garnett GP, Micheus A,Franco EL and Wright TC, editors. VPHvaccines and screening in the prevention ofcervical cancer. Vaccine 2006; 24: Suppl 3;S3: 1-10.3.- Valenzuela M T, De la Hoz F, Koumans E,Posso H, Cavada G, Urquidi C, et al. Carga deenfermedad relacionada con el viruspapiloma humano en paises de AmericaLatina y El Caribe. Towards ComprehensiveCervical Cancer Prevention and ControlRegion of the Americas, Mexico City, 12-13May, 2008.4.- Clifford G M, Gallus S, Herrero R, Munoz N,Snijders P J F, Vaccarella S, and the IARCVPH Prevalence Surveys Study Group.Worldwide distribution of humanpapillomavirus types in cytologically normalwomen in the International Agency forResearch on Cancer VPH prevalencesurveys: a pooled analysis. Lancet 2005;366: 991-8.5.- Franceschi S, Herrero R, Clifford G M,Snijders P J F, Arslan A, Anh PTH, and theIARC VPH Prevalence Surveys Study Group.Variations in the age-specific curves ofhuman papillomavirus prevalence in womenworldwide. Int J Cancer 2006:119; 2677-84.6.- D’Souza G F A, Kreimer A, Viscidi R,Pawlita M, Fakhry C, Koch W M, et al.Case control study of human papillomavirusand oropharyngeal cancer. N Engl J Med2007; 356: 1944-56.7.- Lacey C J N, Lowndes C M, Shah K V.Chapter 4: Burden and management of non-cancerous VPH-related conditions: VPH 6/11 disease. In: Bosch FX, Cuzik J, SchillerJT, Garnett GP, Micheus A, Franco EL andWright TC, editors. VPH vaccines andscreening in the prevention of cervicalcancer. Vaccine 2006; 24 Suppl 3; S3: 35-41.8.- Penaloza- Placencia M, Montoya-Fuentes H,Flores-Martinez S E, Fierro-Velasco F J,Penaloza-Gonzalez J M, Sanchez-Corona J.Molecular identification of 7 humanpapillomavirus types in recurrent respiratorypapillomatosis. Arch Otoralyngol HeadNeck Surg 2000; 126: 1119-23.9.- Burchell A N, Winer R L, de Sanjose S,Franco E L. Chapter 6. Epidemiology andtransmission dynamics of genital VPHinfection. In: Bosch F X, Cuzik J, Schiller JT, Garnett G P, Micheus A, Franco E L andWright T C, editors. VPH vaccines andscreening in the prevention of cervicalcancer. Vaccine 2006; 24 Suppl 3; S3/52-6210.- Moscicki A B, Achiffman M, Kjaer S,Villa L L. Chapter 5: Updating the naturalhistory of HPV and anogenital cancer. In:Bosch F X, Cuzik J, Schiller J T, Garnett GP, Micheus A, Franco E L and Wright T C,editors. VPH vaccines and screening in theprevention of cervical cancer. Vaccine2006; 24 Suppl 3; S3/42-51.11.- Departamento de Estadisticas e Informacionen Salud - Unidad de Cancer Ministerio deSalud, 2004.12.- Citoexpert/Departamento de Estadisticas eInformacion en Salud (DEIS)-Unidad deCancer, Ministerio de Salud, 2005.13.- Donoso E, Cuello M, Villarroel L. Reduccionen la mortalidad por cancer cervico uterinoen Chile, 1990-2003. Rev Chil ObstetGinecol 2006; 71: 307-12.14.- Ferreccio C, Prado R, Luzoro A, Ampuero S,Snijders P, Meijer C, et al. Population-basedprevalence and age distribution of humanpapillomavirus among women in Santiago,Chile. Cancer Epidemiol Biomarkers Prev2004; 13: 2271-615.- Ferreccio C, Corvalan A, Margozzini P,Viviani P, Gonzalez C, Aguilera X, et al.Baseline assessment of prevalence andgeographical distribution of HPV types inChile using self-collected vaginal samples.BMC Public Health 2008; 8: 78 doi:10.1186/1471-2458-8-78.16.- Republica de Chile, Ministerio de Salud.Encuesta Nacional de Salud 2003. Resumenejecutivo. El Vigia (Chile) 2004; 8 (20):1-20.17.- Melo A, Montenegro S, Hooper T,Capurro I, Roa J, Roa I. Tipificacion delvirus papiloma humano (VPH) en lesionespre-neoplasicas y carcinoma del cuellouterino en mujeres de la IX Region-Chile.Rev Med Chile 2003; 131: 1382-90.18.- Valdivia I, Aguayo F, Corvalan A, Pruyas M,Rodriguez T, Ferreccio C. Libro de Resume-nes del XXXI Congreso Chileno de Obstetri-cia y Ginecologia, Vina del Mar 22-24 denoviembre de 2007; pagina 32.19.- CONASIDA, Ministerio de Salud. Enferme-dades de Transmision Sexual, Chile. BoletinNo 2; paginas 6-7.20.- CONASIDA, Ministerio de Salud. Enferme-dades de Transmision Sexual, Chile. BoletinNo 5; paginas 9-10.21.- Valenzuela M T, Pereira A, Cavada G,Pantoja J, Fanjelren V. Implementacionde un sistema de monitoreo y evaluacionen el entorno clinico del cambio decomportamiento de los consultantesde ETS. Informe Final Proyecto FondoGlobal, 2007.22.- Instituto Nacional de la Juventud. CuartaEncuesta Nacional de Juventud. ResultadosGenerales. 2003.23.- Ministerio de Salud de Chile, OMS, OPS,CDC. Encuesta Mundial de Salud Escolar.Chile 2004.24.- Laboratorio Merck. Gardasil

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.

Bocavirus humano: Estudios en la literatura médica y en 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 rates range 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 was detected in 24.2% of nasopharyngeal swabs in children under 5 years of age with respiratory symptoms of which 74% had coinfection with other viruses. In asymptomatic children under 5 years of age, 37.5% of NP samples were positive for HBoV. We discuss the role of HBoV as a causal agent of respiratory and/or enteric disease in light of the high rates of coinfection and asymptomatic infections.

Seguridad de las vacunas que contienen timerosal: Declaración del Comité Consultivo de Inmunizaciones (CCI) de la Sociedad Chilena de Infectología

Thimerosal is a mercury derivative included in vaccines since 1930 with the aim to prevent microbial contamination. During the last decades, the use of thimerosal has been questioned, specifically because of a potential association with neurotoxicity. After a thorough review of published studies on pediatric use of thimerosal-containing vaccines, and of position papers from international expert groups, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases concludes that there is no solid evidence of adverse events associated with the use of thimerosal containing vaccines in infants and children. Therefore, a change in current vaccine practices refererred to thimerosal-containing vaccines is not justified in Chile.

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.

Virus papiloma humano y cáncer cérvico-uterino

Molecular, clinical and epidemiological 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% of women with cervical cancer. 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 Medica de Chile, two papers on HPV are presented. Guzman and colleagues demonstrate that HPV can be detected in 66% to 77% of healthy male adolescents bypolymerase 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 its 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 cancer. The final decision of universal vaccine use in Chile should be based on a through analysis of information.ev Mid Chile