Antimicrobial Resistance of Helicobacter pylori Isolated From Latin American Children and Adolescents (2008-2023): A Systematic Review.

BACKGROUND: Latin America has a high prevalence of Helicobacter pylori in children that may lead to peptic ulcer disease and eventually gastric cancer in adulthood. Successful eradication is hindered by rising antimicrobial resistance. We summarize H. pylori resistance rates in Latin American children from 2008 to 2023. MATERIAL AND METHODS: Systematic review following PRISMA guidelines and National Heart, Lung, and Blood Institute checklist to assess risk of bias (PROSPERO CRD42024517108) that included original cross-sectional observational studies reporting resistance to commonly used antibiotics in Latin American children and adolescents. We searched in PubMed, LILACS, and SciELO databases. RESULTS: Of 51 studies, 45 were excluded. The quality of the six analyzed studies (297 H. pylori-positive samples) was satisfactory. Phenotypic methods (N = 3) reported higher resistance rates than genotypic studies (N = 3). Clarithromycin resistance ranged from 8.0% to 26.7% (6 studies; 297 samples), metronidazole from 1.9% to 40.2% (4 studies; 211 samples), amoxicillin from 0% to 10.4% (3 studies; 158 samples), tetracycline resistance was not detected (3 studies; 158 samples), and levofloxacin resistance was 2.8% (1 study; 36 samples). CONCLUSION: Scarce Latin American studies on H. pylori resistance, along with methodological heterogeneity, hinder conclusive findings. Clarithromycin and metronidazole (first-line drugs) resistance is worrisome, likely impacting lower eradication rates. Urgent systematic surveillance or individual testing before treatment is necessary to enhance eradication.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Prevalence in Blood in a Large School Community Subject to a Coronavirus Disease 2019 Outbreak: A Cross-sectional Study.

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. METHODS: The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4-19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. RESULTS: The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2-11.8) for 1009 students and 16.6% (95% CI, 12.1-21.9) for 235 staff. Among students, positivity was associated with a younger age (P = .01), a lower grade level (P = .05), prior real-time polymerase chain reaction (RT-PCR) positivity (P = .03), and a history of contact with a confirmed case (P < .001). Among staff, positivity was higher in teachers (P = .01) and in those previously RT-PCR positive (P < .001). Excluding RT-PCR-positive individuals, antibody positivity was associated with fever in adults and children (P = .02 and P = .002, respectively), abdominal pain in children (P = .001), and chest pain in adults (P = .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (P = .01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings.

Predominance of Rotavirus G8P[8] in a City in Chile, a Country Without Rotavirus Vaccination.

Rotavirus G8P[8] infection has been common in Africa, but rare in the Americas. Among 23 rotavirus episodes observed during 18 months of surveillance of 100 families in Chile, 11 (48%) were identified as G8P[8]. Genotypes from these strains shared >99% identity with rotavirus sequences described in Asia, and may be misclassified as mixed G8/G12.

Intestinal Immunity to Poliovirus Following Sequential Trivalent Inactivated Polio Vaccine/Bivalent Oral Polio Vaccine and Trivalent Inactivated Polio Vaccine-only Immunization Schedules: Analysis of an Open-label, Randomized, Controlled Trial in Chilean Infants.

Background: Identifying polio vaccine regimens that can elicit robust intestinal mucosal immunity and interrupt viral transmission is a key priority of the polio endgame. Methods: In a 2013 Chilean clinical trial (NCT01841671) of trivalent inactivated polio vaccine (IPV) and bivalent oral polio vaccine (bOPV; targeting types 1 and 3), infants were randomized to receive IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV at 8, 16, and 24 weeks of age and challenged with monovalent oral polio vaccine type 2 (mOPV2) at 28 weeks. Using fecal samples collected from 152 participants, we investigated the extent to which IPV-bOPV and IPV-only immunization schedules induced intestinal neutralizing activity and immunoglobulin A against polio types 1 and 2. Results: Overall, 37% of infants in the IPV-bOPV groups and 26% in the IPV-only arm had detectable type 2-specific stool neutralization after the primary vaccine series. In contrast, 1 challenge dose of mOPV2 induced brisk intestinal immune responses in all vaccine groups, and significant rises in type 2-specific stool neutralization titers (P < .0001) and immunoglobulin A concentrations (P < 0.0001) were measured 2 weeks after the challenge. In subsidiary analyses, duration of breastfeeding also appeared to be associated with the magnitude of polio-specific mucosal immune parameters measured in infant fecal samples. Conclusions: Taken together, these results underscore the concept that mucosal and systemic immune responses to polio are separate in their induction, functionality, and potential impacts on transmission and, specifically, provide evidence that primary vaccine regimens lacking homologous live vaccine components are likely to induce only modest, type-specific intestinal immunity.

Impact of Maternal Antibody on the Immunogenicity of Inactivated Polio Vaccine in Infants Immunized With Bivalent Oral Polio Vaccine: Implications for the Polio Eradication Endgame.

Background: Quantifying interference of maternal antibodies with immune responses to varying dose schedules of inactivated polio vaccine (IPV) is important for the polio endgame as IPV replaces oral polio vaccine (OPV). Methods: Type 2 poliovirus humoral and intestinal responses were analyzed using pre-IPV type 2 seropositivity as proxy for maternal antibodies from 2 trials in Latin America. Infants received 1 or 2 doses of IPV in sequential IPV-bivalent oral polio vaccine (bOPV) or mixed bOPV-IPV schedules. Results: Among infants vaccinated with bOPV at age 6, 10, and 14 weeks of age and IPV at 14 weeks, those with type 2 pre-IPV seropositivity had lower seroprotection rates than seronegative infants at 4 weeks (92.7% vs 83.8%; difference, 8.9% [95% confidence interval, 0.6%-19.9%]; n = 260) and 22 weeks (82.7% vs 60.4%; difference, 22.3 [12.8%-32.4%]; n = 481) post-IPV. A second IPV at age 36 weeks resulted in 100% seroprotection in both groups. Among infants vaccinated with 1 IPV at age 8 weeks followed by 2 doses of bOPV, pre-IPV type 2-seropositive infants had lower seroprotection at age 28 weeks than those who were seronegative (93.0% vs 73.9%; difference, 19.6% [95% confidence interval, 7.3%-29.4%]; n = 168). A second dose of IPV at 16 weeks achieved >97% seroprotection at age 24 or 28 weeks, regardless of pre-IPV status. Poliovirus shedding after challenge with monovalent OPV, serotype 2, was higher in pre-IPV seropositive infants given sequential IPV-bOPV. No differences were observed in the mixed bOPV-IPV schedule. Conclusions: The presence of maternal antibody is associated with lower type 2 post-IPV seroprotection rates among infants who receive a single dose of IPV. This impact persists until late in infancy and is overcome by a second IPV dose.

Review: Prevalence and dynamics of Helicobacter pylori infection during childhood.

INTRODUCTION: Long-term persistent Helicobacter pylori infection has been associated with ulceropeptic disease and gastric cancer. Although H. pylori is predominantly acquired early in life, a clear understanding of infection dynamics during childhood has been obfuscated by the diversity of populations evaluated, study designs, and methods used. AIM: Update understanding of true prevalence of H. pylori infection during childhood, based on a critical analysis of the literature published in the past 5 years. METHODS: Comprehensive review and meta-analysis of original studies published from 2011 to 2016. RESULTS: A MEDLINE® /PubMed® search on May 1, 2016, using the terms pylori and children, and subsequent exclusion, based on abstract review using predefined criteria, resulted in 261 citations. An Embase® search with the same criteria added an additional 8 citations. In healthy children, meta-analysis estimated an overall seroprevalence rate of 33% (95% CI: 27%-38%). Seven healthy cohort studies using noninvasive direct detection methods showed infection prevalence estimates ranging from 20% to 50% in children ≤5 and 38% to 79% in children >5 years. The probability of infection persistence after a first positive sample ranged from 49% to 95%. Model estimates of cross-sectional direct detection studies in asymptomatic children indicated a prevalence of 37% (95% CI: 30%-44%). Seroprevalence, but not direct detection rates increased with age; both decreased with increasing income. The model estimate based on cross-sectional studies in symptomatic children was 39% (95% CI: 35%-43%). CONCLUSIONS: The prevalence of H. pylori infection varied widely in the studies included here; nevertheless, model estimates by detection type were similar, suggesting that overall, one-third of children worldwide are or have been infected. The few cohort and longitudinal studies available show variability, but most studies, show infection rates over 30%. Rather surprisingly, overall infection prevalence in symptomatic children was only slightly higher, around 40%. Studies including only one positive stool sample should be interpreted with caution as spontaneous clearance can occur.

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.

Detection of Helicobacter pylori by Real-Time PCR for 16s rRNA in Stools of NonInfected Healthy Children, Using ELISA Antigen Stool Test as the Gold Standard.

BACKGROUND: We previously detected Helicobacter pylori infection by stool antigen ELISA assay in 33-41% of asymptomatic Chilean children between 2-3 years of age, of which 11-20% had a transient infection and 21-22% a persistent infection. A total of 88% of ELISA-positive samples were also rtPCR positive, while 37/133 (33%) of ELISA-negative stool samples were rtPCR positive. The significance of a ELISA-negative/rtPCR-positive sample requires clarification. We aimed to determine whether rtPCR is able to detect persistent infections not detected by ELISA. MATERIALS AND METHODS: We selected 36 children with an ELISA-negative/rtPCR-positive stool sample, of which 25 were never H. pylori infected according to ELISA, and 11 had a transient infection with an ELISA-positive sample before or after the discordant sample. At least two additional consecutive ELISA-negative samples per child were tested in duplicate by rtPCR for the 16s rRNA gene. RESULTS: A total of 14 of 78 (17.9%) rtPCR reactions were positive, but only 4/78 (5.1%) were positive in both duplicates, representing a total of 3/36 (8.3%) children with an additional rtPCR-positive sample, only one of whom was persistently negative by ELISA. One child with a transient infection had two positive rtPCR reactions despite negative ELISA samples. CONCLUSIONS: In H. pylori noninfected or transiently infected children, as determined by stool ELISA, additional ELISA-negative/rtPCR-positive stool samples were found in 8.3% of children, but a possible persistent infection was only identified in 2.7% of children. Thus, the characterization of infection dynamics in children is not being misrepresented by application of stool ELISA. Furthermore, rtPCR does not significantly improve dynamic characterization.

The fecal virome of South and Central American children with diarrhea includes small circular DNA viral genomes of unknown origin.

Viral metagenomics of feces collected from 58 Peruvian children with unexplained diarrhea revealed several small circular ssDNA genomes. Two genomes related to sequences previously reported in feces from chimpanzees and other mammals and recently named smacoviruses were characterized and then detected by PCR in 1.7 % (1/58) and 19 % (11/58) of diarrheal samples, respectively. Another three genomes from a distinct small circular ssDNA viral group provisionally called pecoviruses encoded Cap and Rep proteins with <35 % identity to those in related genomes reported in human, seal, porcine and dromedary feces. Pecovirus DNA was detected in 15.5 % (9/58), 5.9 % (3/51) and 3 % (3/100) of fecal samples from unexplained diarrhea in Peru, Nicaragua and Chile, respectively. Feces containing these ssDNA genomes also contained known human enteric viral pathogens. The cellular origins of these circular ssDNA viruses, whether human cells, ingested plants, animals or fungal foods, or residents of the gut microbiome, are currently unknown.

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.

[Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer]. / Seroconversión frente a primovacunación reforzada contra hepatitis B en niños con cáncer.

INTRODUCTION: Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. PATIENTS AND METHOD: Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 µg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 µg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. RESULTS: A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml. CONCLUSIONS: Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses.

Transdisciplinary research before, during and after COVID-19 vaccination in Chile: a virtuoso collaboration with future perspectives.

The COVID-19 pandemic presented numerous challenges that required immediate attention to mitigate its devastating consequences on a local and global scale. In March 2020, the Chilean government, along with health and science authorities, implemented a strategy aimed at generating relevant evidence to inform effective public health decisions. One of the key strengths of this strategy was the active involvement of the scientific community, employing transdisciplinary approaches to address critical questions and support political decision-making. The strategy promoted collaborations between the government, public and private institutions, and transdisciplinary academic groups throughout each phase of the pandemic. By focusing on pressing problems and questions, this approach formed the foundation of this report which reflects the collaborative effort throughout the pandemic of individuals from the Instituto de Sistemas Complejos de Ingeniería (ISCI), the Faculty of Medicine of the University of Chile, government authorities and industry. Early in the pandemic, it became crucial to gather evidence on how to minimize the impact of infection and disease while awaiting the availability of vaccines. This included studying the dynamics of SARS-CoV-2 infection in children, assessing the impact of quarantines on people's mobility, implementing strategies for widespread SARS-CoV-2 polymerase chain reaction (PCR) testing, and exploring pool testing for large populations. The urgent need to reduce disease severity and transmission posed a significant challenge, as it was essential to prevent overwhelming healthcare systems. Studies were conducted to predict ICU bed requirements at the local level using mathematical models. Additionally, novel approaches, such as using cellphone mobility-based technology to actively identify infected individuals, and to optimize population sampling, were explored following the first wave of the pandemic. Chile took early action in addressing vaccination through a high-level scientific board, before vaccines became available. Studies conducted during this period included population-based immunologic evaluations of different vaccines, which helped build confidence in the population and supported the need for booster doses and potential vaccination of children. These studies and collaborations, which will be discussed here, have provided valuable insights and will inform future approaches in a post-pandemic world. Importantly, highly conservative estimates indicate that 3,000 lives and more than 300 million USD were saved by this academic-public-private collaborative effort.

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.

Acute diarrhea in West African children: diverse enteric viruses and a novel parvovirus genus.

Parvoviruses cause a variety of mild to severe symptoms or asymptomatic infections in humans and animals. During a viral metagenomic analysis of feces from children with acute diarrhea in Burkina Faso, we identified in decreasing prevalence nucleic acids from anelloviruses, dependoviruses, sapoviruses, enteroviruses, bocaviruses, noroviruses, adenoviruses, parechoviruses, rotaviruses, cosavirus, astroviruses, and hepatitis B virus. Sequences from a highly divergent parvovirus, provisionally called bufavirus, were also detected whose NS1 and VP1 proteins showed <39% and <31% identities to those of previously known parvoviruses. Four percent of the fecal samples were PCR positive for this new parvovirus, including a related bufavirus species showing only 72% identity in VP1. The high degree of genetic divergence of these related genomes from those of other parvoviruses indicates the presence of a proposed new Parvoviridae genus containing at least two species. Studies of the tropism and pathogenicity of these novel parvoviruses will be facilitated by the availability of their genome sequences.

Infection with SARS-CoV-2 variant Gamma (P.1) in Chile increased ICU admission risk three to five-fold.

The 2021 wave of SARS-CoV-2 infection in Chile was characterized by an explosive increase in ICU admissions, which disproportionately affected individuals younger than 60 years. This second wave was also accompanied by an explosive increase in Gamma (P.1) variant detections and the massive vaccine rollout. We unveil the role the Gamma variant played in stressing the use of critical care, by developing and calibrating a queueing model that uses data on new onset cases and actual ICU occupancy, symptom's onset to ICU admission interval, ICU length-of-stay, genomic surveillance, and vaccine effectiveness. Our model shows that infection with the Gamma (P.1) variant led to a 3.5-4.7-fold increase in ICU admission for people younger than 60 years. This situation occurred on top of the already reported higher infection rate of the Gamma variant. Importantly, our results also strongly suggest that the vaccines used in Chile (inactivated mostly, but also an mRNA), were able to curb Gamma variant ICU admission over infections.

Vaccine value profile for norovirus.

Norovirus is attributed to nearly 1 out of every 5 episodes of diarrheal disease globally and is estimated to cause approximately 200,000 deaths annually worldwide, with 70,000 or more among children in developing countries. Noroviruses remain a leading cause of sporadic disease and outbreaks of acute gastroenteritis even in industrialized settings, highlighting that improved hygiene and sanitation alone may not be fully effective in controlling norovirus. Strengths in global progress towards a Norovirus vaccine include a diverse though not deep pipeline which includes multiple approaches, including some with proven technology platforms (e.g., VLP-based HPV vaccines). However, several gaps in knowledge persist, including a fulsome mechanistic understanding of how the virus attaches to human host cells, internalizes, and induces disease.

Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development.

Vibrio cholerae is the causative agent of cholera, a highly contagious diarrheal disease affecting millions worldwide each year. Cholera is a major public health problem, primarily in countries with poor sanitary conditions and regions affected by natural disasters, where access to safe drinking water is limited. In this narrative review, we aim to summarize the current understanding of the evolution of virulence and pathogenesis of V. cholerae as well as provide an overview of the immune response against this pathogen. We highlight that V. cholerae has a remarkable ability to adapt and evolve, which is a global concern because it increases the risk of cholera outbreaks and the spread of the disease to new regions, making its control even more challenging. Furthermore, we show that this pathogen expresses several virulence factors enabling it to efficiently colonize the human intestine and cause cholera. A cumulative body of work also shows that V. cholerae infection triggers an inflammatory response that influences the development of immune memory against cholera. Lastly, we reviewed the status of licensed cholera vaccines, those undergoing clinical evaluation, and recent progress in developing next-generation vaccines. This review offers a comprehensive view of V. cholerae and identifies knowledge gaps that must be addressed to develop more effective cholera vaccines.

COVID-19 lateral flow IgG seropositivity and serum neutralising antibody responses after primary and booster vaccinations in Chile: a cross-sectional study.

BACKGROUND: By June 30, 2022, 92·6% of the Chilean population older than 18 years had received a full primary SARS-CoV-2 vaccine series, mostly with CoronaVac (Sinovac Biotech), and 78·4% had received a booster dose, mostly heterologous with BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (AstraZeneca). We previously reported national seroprevalence data from lateral flow testing of IgG SARS-CoV-2 antibodies up to 16 weeks after primary vaccination. Our aim here was to study IgG seropositivity dynamics up to 30 weeks after primary vaccination and, in CoronaVac recipients, up to 26 weeks after booster vaccination, and to establish the correlation between lateral flow tests and neutralising antibody titres. METHODS: In this cross-sectional study, testing stations for SARS-CoV-2 IgG detection were selected and installed from March 12, 2021, in hotspots in 24 large Chilean cities, and were maintained until March 31, 2022. Individuals voluntarily approaching the testing stations were invited to perform a rapid lateral flow test via a finger prick and complete a questionnaire. Between Aug 12, 2021, and April 1, 2022, volunteers seeking medical care in the Mutual de Seguridad de la Cámara Chilena de la Construcción provided blood samples for lateral flow testing and neutralising antibody studies; inclusion criteria were age at least 18 years, history of complete primary vaccination series with CoronaVac, BNT162b2, or ChAdOx1, or no vaccine, and no previous COVID-19 diagnosis. We tested the difference in IgG positivity across time, and between primary and booster doses, in all eligible participants with complete records, controlling for age, gender, and comorbidities. We also assessed the predictive power of neutralising antibody titres and sociodemographic characteristics on the probability of IgG positive results using multivariable logistic regression. FINDINGS: Of 107 220 individuals recruited at the testing stations, 101 070 were included in our analysis (59 862 [59·2%] women and 41 208 [40·8%] men). 65 902 (65·2%) received primary vaccination series with CoronaVac, 18 548 (18·4%) with BNT162b2, and 606 (0·6%) with ChAdOx1, and 16 014 (15·8%) received no vaccine. Among the 61 767 individuals with a complete primary vaccination series with CoronaVac, 608 (1·0%) received a CoronaVac booster, 10 095 (16·3%) received a BNT162b2 booster, and 5435 (8·8%) received a ChAdOx1 booster. After ChAdOx1 primary vaccination, seropositivity peaked at week 5 after the second dose, occurring in 13 (92·9%, 95% CI 79·4-100·0) of 14 individuals. In participants who received a complete CoronaVac primary series, the decline in seropositivity stabilised at week 18 after the second dose (86 [44·7%, 95% CI 41·8-47·7] of 1087 individuals), whereas after receiving BNT162b2, seropositivity declined slightly by week 25 after the second dose (161 [94·2%, 90·6-97·7] of 171). A lower proportion of individuals who received the CoronaVac primary series and a homologous booster were seropositive (279 [85·6%, 95% CI 81·8-89·4] of 326) by weeks 2-18 than those who received a BNT162b2 booster (7031 [98·6%, 98·4-98·9] of 7128) or a ChAdOx1 booster (2893 [98·0%, 97·5-98·5] of 2953). The correlation between IgG positivity and log of the infectious dose in 50% of neutralising antibodies was moderate, with a sensitivity of 81·4% (95% CI 76·3-86·6) and specificity of 92·5% (73·3-100·0). INTERPRETATION: Dynamic monitoring of IgG positivity to SARS-CoV-2 can characterise antibody waning over time in the absence or presence of booster doses, providing relevant data for the design of vaccination strategies. The correlation between lateral flow test IgG titres and neutralising antibody concentrations suggests that they could be a quick and effective surveillance tool to measure protection against SARS-CoV-2. FUNDING: Instituto Sistemas Complejos de Ingeniería, Subsecretaría de Redes Asistenciales, Ministry of Health, Chile, and Mutual de Seguridad de la Cámara Chilena de la Construcción.