The human gut microbiome of Latin America populations: a landscape to be discovered.

PURPOSE OF REVIEW: The gut microbiome is critical for human health, and its alteration is associated with intestinal, autoimmune and metabolic diseases. Numerous studies have focused on prevention or treatment of dysbiotic microbiome to reduce the risk or effect of these diseases. A key issue is to define the microbiome associated with the state of good health. The purpose of this review is to describe factors influencing the gut microbiome with special emphasis on contributions from Latin America. In addition, we will highlight opportunities for future studies on gut microbiome in Latin America. RECENT FINDINGS: A relevant factor influencing gut microbiome composition is geographical location associated with specific genetic, dietary and lifestyle factors. Geographical specificities suggest that a universal 'healthy microbiome' is unlikely. SUMMARY: Several research programs, mostly from Europe and North America, are extensively sequencing gut microbiome of healthy people, whereas data from Latin America remain scarce yet slowly increasing. Few studies have shown difference in the composition of gut microbiome between their local populations with that of other industrialized countries (North American populations). Latin America is composed of countries with a myriad of lifestyles, traditions, genetic backgrounds and socioeconomic conditions, which may determine differences in gut microbiome of individuals from different countries. This represents an opportunity to better understand the relationship between these factors and gut microbiome.

Persistent and transient Helicobacter pylori infections in early childhood.

BACKGROUND: Helicobacter pylori, the main cause of peptic ulcer disease and gastric cancer in adult populations, is generally acquired during the first years of life. Infection can be persistent or transient and bacterial and host factors determining persistence are largely unknown and may prove relevant for future disease. METHODS: Two cohorts of healthy Chilean infants (313 total) were evaluated every 3 months for 18-57 months to determine pathogen- and host-factors associated with persistent and transient infection. RESULTS: One-third had at least one positive stool ELISA by age 3, with 20% overall persistence. Persistent infections were acquired at an earlier age, associated with more household members, decreased duration of breastfeeding, and nonsecretor status compared to transient infections. The cagA positive strains were more common in persistent stools, and nearly 60% of fully characterized persistent stool samples amplified cagA/vacAs1m1. Persistent children were more likely to elicit a serologic immune response, and both infection groups had differential gene expression profiles, including genes associated with cancer suppression when compared to healthy controls. CONCLUSIONS: These results indicate that persistent H. pylori infections acquired early in life are associated with specific host and/or strain profiles possibly associated with future disease occurrence.

Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

BACKGROUND: Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. METHODS: We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. FINDINGS: Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (p<0·0145) and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose; seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified. INTERPRETATION: On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys. FUNDING: Novartis Vaccines and Diagnostics.

A cross sectional study found differential risks for COVID-19 seropositivity amongst health care professionals in Chile.

OBJECTIVE: Health care workers (HCWs) are at increased risk for SARS-CoV-2 infection, however not all face the same risk. We aimed to determine IgG/IgM prevalence and risk factors associated with seropositivity in Chilean HCWs. STUDY DESIGN AND SETTING: This was a nationwide, cross-sectional study including a questionnaire and COVID-19 lateral flow IgG/IgM antibody testing. All HCWs in the Chilean public health care system were invited to participate following the country's first wave. RESULTS: IgG/IgM positivity in 85,529 HCWs was 7.2%, ranging from 1.6% to 12.4% between regions. Additionally, 9.7% HCWs reported a positive PCR of which 47% were seropositive. Overall, 10,863 (12.7%) HCWs were PCR and/or IgG/IgM positive. Factors independently associated with increased odds ratios (ORs) for seropositivity were: working in a hospital, night shifts, contact with Covid-19, using public transport, male gender, age>45, BMI ≥30, and reporting ≥2 symptoms. Stress and/or mental health disorder and smoking were associated with decreased ORs. These factors remained significant when including PCR positive cases in the model. CONCLUSIONS: HCWs in the hospital were at highest risk for COVID-19, and several independent risk factors for seropositivity and/or PCR positivity were identified.

Rotavirus vaccines for the developing world.

PURPOSE OF REVIEW: The authors discuss the most relevant information in the field of rotavirus vaccines published from October 2007 to June 2009; new information on the virus, host response and disease burden that relate to our understanding of vaccine mechanisms and impact are discussed. The review will focus on the role of the vaccines for the developing world but this does not preclude the relevance of these vaccines for children living in the industrialized world. RECENT FINDINGS: Immune mechanisms involved in rotavirus-associated immunity potentially relevant for vaccine-associated immunity continue to be identified including anti-NSP4 antibodies, cellular and mucosal mechanisms. Rotavirus-associated disease burden is high, causing approximately 40% of diarrhea-associated hospitalizations in children less than 5 years of age worldwide; G12, G8 and P[6] antigenic types emerging in developing countries are increasing in prevalence and may share worldwide circulation with the other five more common serotypes. The two currently available vaccines, based on different immune concepts, (VP7/VP4 homotypic specificity for RotaTeq vs. homotypic and heterotypic specificity for Rotarix) have demonstrated high and sustained efficacy in middle and high-income countries. Recent efficacy and effectiveness studies demonstrate acceptable protection levels in the poorest countries of the world against most antigenic types, leading to universal vaccine recommendation. Postlicensure surveillance has not detected any signal of increased risk for intussusception in children vaccinated with any of the two vaccines. SUMMARY: Rotavirus vaccines are well tolerated and provide adequate protection against moderate to severe disease in high, middle and low-income regions. Partnerships between governments, industry, and funding agencies will now be urgently needed to promote vaccine use, especially in the less privileged countries of the world.

Rotavirus Serum IgA Immune Response in Children Receiving Rotarix Coadministered With bOPV or IPV.

BACKGROUND: Vaccine schedules including bivalent oral and inactivated poliovirus vaccines will replace trivalent oral poliovirus vaccines in 2016. METHODS: We evaluated rotavirus immunoglobulin A seroresponses when the second dose of Rotarix at 16 weeks was given concomitantly with inactivated or bivalent oral poliovirus vaccines. RESULTS: Rotavirus immunoglobulin A seroresponse rate at week 28 was 15% lower in recipients of bivalent oral poliovirus vaccines compared with inactivated poliovirus vaccines. CONCLUSION: Bivalent oral poliovirus vaccine decreases rotavirus IgA seroresponse rates when coadministered at 16 weeks of age.

Early hospital discharge followed by outpatient management versus continued hospitalization of children with cancer, fever, and neutropenia at low risk for invasive bacterial infection.

PURPOSE: To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI). PATIENTS AND METHODS: Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires. RESULTS: A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US 638 dollars (95% CI, 572 dollars to 703 dollars) and US 903 dollars (95% CI, 781 dollars to 1,025 dollars) for the ambulatory and hospital-based groups, respectively (P =.003). CONCLUSION: For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.

Dynamics of Helicobacter pylori detection in stools during the first 5 years of life in Chile, a rapidly developing country.

BACKGROUND: : Helicobacter pylori colonization/infection can be transitory or persistent, conditions that have not been thoroughly evaluated in young children. We aimed to characterize the dynamics of H. pylori stool detection and to determine host and environmental factors and symptoms associated with persistence. METHOD: : In a 5-year cohort study, we followed-up infants from birth with clinic visits every 3 months. Symptoms and environmental risk factor survey and a stool sample for H. pylori antigen detection were requested in every visit. Secretor/ABH histo-blood group phenotype was determined in saliva. RESULTS: : Overall, 218 of 1456 (15%) stool samples were positive for H. pylori and 39 of 96 (41%) children had at least 1 positive sample. Stool detection was transitory in 16 of 39 (41%), persistent in 19 (49%) and undetermined in 4 (10%) children. Persistence was acquired largely during the first 24 months (17/19 cases) and was associated with nonsecretor phenotype (32% versus 0% for transitory infection; P = 0.02) and daycare attendance (67% versus 26% for never infected; P = 0.019). Symptoms possibly associated with persistence were referred in only 1 child. CONCLUSIONS: : Nearly 20% of this Chilean cohort had persistent H. pylori stool sample detections during the first 5 years of life, acquired mostly during the first 24 months. Persistence was significantly associated with nonsecretor phenotype and daycare attendance, and possibly associated gastrointestinal symptoms were rare. This relatively common group of young children with persistent H. pylori colonization/infection will require further study.

Enteric viruses in wastewaters: an interesting approach to evaluate the potential impact of rotavirus vaccination on viral circulation.

Rotavirus and norovirus are the leading causes of acute gastroenteritis worldwide. Both viruses share features such as low infectious dose, high stool concentration and prolonged survival in the environment, including water. However, they differ in several aspects, reflecting potential differences in their interactive capacities with the environment and host. This work, which is a 13-month prospective study in a developing country with high rotavirus vaccine coverage demonstrated a high (44%) PCR detection of norovirus in 84 wastewater samples compared with a relatively low (11%) detection of rotavirus. These results suggest that rotavirus circulation may be positively affected by vaccination and support the use of enteric viral detection in wastewaters as a useful tool to measure the impact of specific interventions.

Prospective characterization of norovirus compared with rotavirus acute diarrhea episodes in chilean children.

BACKGROUND: Rotavirus and more recently noroviruses are recognized as main causes of moderate to severe acute diarrhea episodes (ADE) in children < or =5 years of age. Comparing epidemiologic and clinical features of norovirus to rotavirus ADE will aid in the decision-making process required to develop norovirus vaccines. METHODS: Surveillance for ADE occurring in children < or =5 years of age was implemented in the emergency department (ED) and ward of a large hospital in Santiago and Valparaiso, and in 4 outpatient clinics in Santiago. A stool sample was obtained within 48 hours of consultation for rotavirus detection by enzyme-linked immunosorbent assay and noroviruses by enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction. For ED and hospital rotavirus and norovirus ADE parents were instructed to monitor clinical findings associated with severity until the end of the episode. The 20-point Vesikari score was used to determine disease severity. RESULTS: Between July 2006 and October 2008 rotavirus and noroviruses were detected in 331 (26%) and 224 (18%) of 1913 ADE evaluated. The proportion of rotavirus-positive samples in hospital ward, ED, and outpatient clinic was 40%, 26% to 30%, and 13% compared with 18%, 17% to 19%, and 14% for noroviruses. Mean age and 25%-75% interquartile interval of children with rotavirus and norovirus ADE were remarkably similar, 15.6 months (9-20), and 15.5 months (9-19), respectively. Rotavirus cases displayed an autumn-winter peak followed 2 to 3 months later by the norovirus peak. The mean (interquartile) for the Vesikari score was 12.9 (11-15) and 11.9 (9-14.5) for rotavirus (N = 331) and norovirus (N = 224) ADE, respectively, P = 0.003. Compared with norovirus, rotavirus ADE were more common in the 11 to 16 severity score interval (P = 0.006), had a higher maximum stool output in a given day (P = 0.01) and more frequent fever (P < 0.0001). Duration of diarrhea, presence, duration and intensity of vomiting, and intensity of fever did not differ between viruses. Mixed rotavirus and norovirus infections were uncommon (<1%) and not clinically more severe. Clinical severity of ADE in young infants was similar for rotavirus and lower (P = 0.03) for noroviruses compared with older children. CONCLUSION: Noroviruses are a significant cause of moderate to severe endemic ADE in Chilean children. Although significantly less severe than rotavirus as a group, most norovirus episodes were moderate to severe clinically. An effective norovirus vaccine would be of significant additional benefit to the current rotavirus vaccine in decreasing disease burden associated with ADE.

Symptomatic and asymptomatic rotavirus and norovirus infections during infancy in a Chilean birth cohort.

BACKGROUND: Rotavirus and more recently norovirus have been recognized as 2 of the most common causes of acute diarrhea in children. Comparative analysis of these infections in a birth cohort has not been performed and can provide relevant insight on clinical and viral behaviors. METHODS: Mother-infant pairs from middle-low socioeconomic background living in the Metropolitan Region of Chile are being followed for 18 months in 2 outpatient clinics. Infants are evaluated monthly for asymptomatic excretion of rotavirus and norovirus and during acute diarrhea episodes (ADE) for rotavirus, norovirus, and bacterial enteropathogens. Severity of ADE is evaluated using the Vesikari score. RESULTS: Between July 1, 2006 and September 1, 2008 a total of 198 children were followed for a mean of 15.7 months. Asymptomatic rotavirus and norovirus infections were detected in 1.3% and 8% of 2278 stool samples compromising 14% and 57% of infants, respectively. Incidence of ADE was approximately 0.8 for the first year of life and approximately 0.6 for the 13 to 18 month age group. Rotavirus and norovirus were detected in 15% and 18% of 145 ADE evaluated. Mean Vesikari score was 10.4 and 7.4 for rotavirus and norovirus respectively (P = 0.01) and severity was not associated with age of patients for either virus. Reinfections were more common for norovirus asymptomatic episodes: 44% versus 19% (P = 0.01) and borderline for symptomatic episodes: 40% versus 11% (P = 0.08). Rotavirus genotype G9P8 and norovirus genogroup II (GII) predominated although most asymptomatic episodes for both viruses were nontypable. None of 19 symptomatic GII norovirus infections had a previous documented GII infection compared with 10 of 31 asymptomatic GII infections (OR = 0. 95% CL = 0, 0.59; P = 0.008). CONCLUSIONS: Children had suffered a mean of approximately 1.4 ADE by 18 months of age of which 15% and 18% were caused by rotavirus and norovirus, respectively. In general rotavirus infections were more severe than norovirus infections and for both viruses severity was not related to age. Norovirus reinfections were significantly more common than rotavirus reinfections but for GII norovirus a primary infection seems to confer protection against clinically significant reinfections.

Novel recombinant norovirus causing outbreaks of gastroenteritis in Santiago, Chile.

Capsid and polymerase (RdRp) genes of 13 norovirus outbreak strains from Chile were compared. The genes sequences were discordant for five strains, and recombination was confirmed for two of them by amplification of a 1,360-bp gene segment containing a fragment of both genes. These strains belonged to a novel genogroup by RdRp sequence and to genogroup GII/3 by capsid sequence. Determining the clinical and epidemiological impact of human calicivirus recombination will require future studies.

Caliciviruses and foodborne gastroenteritis, Chile.

Human caliciviruses caused 45% of 55 gastroenteritis outbreaks occurring in Santiago, Chile, during 2000-2003. Outbreaks affected ?99 persons, occurred most commonly in the home, and were associated with seafood consumption. Thirteen outbreak strains sequenced were noroviruses, including 8 GII, 2 GI, and 3 belonging to a novel genogroup.