Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey.

BACKGROUND: Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. METHODS: A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. RESULTS: The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. CONCLUSIONS: The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

Nine-Month Trend of IgG Antibody Persistence and Associated Symptoms Post-SARS-CoV-2 Infection.

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.

Post-therapeutic cure criterion in chronic Chagas disease using Trypanosoma cruzi chimeric proteins.

Chagas disease (CD) is a neglected disease caused by Trypanosoma cruzi Chagas, 1909. Causative treatment can be achieved with two drugs: benznidazole or Nifurtimox. There are some gaps that hinder progress in eradicating the disease. There is no test that can efficiently assess cure control after treatment. Currently, the decline in anti-T. cruzi antibody titres is assessed with conventional serological tests, which can take years. However, the search for new markers of cure must continue to fill this gap. The present study aimed to evaluate the decline in serological titres using chimeric proteins after treatment with benznidazole in chronic patients diagnosed with CD. It was a prospective cross-sectional cohort study between 2000 and 2004 of T. cruzi-positive participants from the Añatuya region (Argentina) treated with benznidazole. Serum samples from ten patients were collected before treatment (day zero) and after the end of treatment (2, 3, 6, 12, 24 and 36 months). For the detection of anti-T. cruzi antibodies, an indirect ELISA was performed using two chimeric recombinant proteins (IBMP-8.1 and IBMP-8.4) as antigens. The changes in reactivity index within the groups before and after treatment were evaluated using the Friedman test. All participants experienced a decrease in serological titres after treatment with benznidazole, especially IBMP-8.1. However, due to the small number of samples and the short follow-up period, it is premature to conclude that this molecule serves as a criterion for sustained cure. Further studies are needed to validate tests based on these or other biomarkers to demonstrate parasitological cure.

Immune response to SARS-CoV-2 variants after immunization with different vaccines in Mexico.

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time.

Eco-epidemiological study of seropositivity against Rickettsia and Leptospira agents in rural areas of Urabá, Colombia.

Rickettsioses and leptospirosis are infectious diseases that are often underdiagnosed due to a lack of knowledge about their epidemiology, pathophysiology, diagnosis, management, among others. Objetive: to characterize the seroprevalence and seroincidence of both Rickettsia and Leptospira agents and determine the risk factors for these outcomes in rural areas of Urabá, Antioquia. Methods: a secondary data analysis using information on Rickettsia and Leptospira exposure from a prior prospective study that explored sociocultural and ecological aspects of Rickettsia infection in rural Urabá, Colombia. A multinomial mixed logistic regression model was employed to analyze factors linked to seroprevalent cases of Rickettsia, Leptospira and both, along with descriptive analyses of seroincident cases. Results: the concomitant seroprevalence against Rickettsiaand Leptospira was 9.38% [95%CI 6.08%-13.37%] (56/597). The factors associated with this seroprevalence were age (ORa= 1.02 [95%CI 1.007-1.03]), male gender (ORa= 3.06 [95%CI 1.75-5.37]), fever history (ORa= 1.71 [95%CI 1.06-2.77]) the presence of breeding pigs (ORa= 2.29 [95%CI 1.36-3.88]), peridomicile yucca crops(ORa= 2.5 [95%CI 1.1-5.62]), and deforestation practices(ORa= 1.74 [95%CI 1.06-2.87]). The concomitant seroincidence against Rickettsia and Leptospira was 1.09% (3/274) [95%CI 0.29%-4.05%], three cases were female, with a median age of 31.83 years-old (IQR 8.69-56.99). At the household level, all the seroincident cases had households built partially or totally with soil floors, wooden walls, and zinc roofs. Two seroincident cases described the presence of equines, canines, and domestic chickens in intra or peri-domicile. Finally, two cases were exposed to synanthropic rodents, and one case to tick infestation. Conclusion: there is evidence of seroprevalent and seroincident cases of seropositivity against both Rickettsia and Leptospira in rural areas of Urabá, Colombia. These findings can help improve public health surveillance systems in preventing, detecting, and attending to the different clinical cases caused by these pathogens.

A novel nomogram for predicting HBeAg seroclearance in HBeAg-positive chronic hepatitis B patients treated with nucleos(t)ide analogues.

INTRODUCTION AND OBJECTIVES: Seroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). PATIENTS AND METHODS: Five hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. RESULTS: The overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (< 79.51) in both sets (P < 0.01). CONCLUSIONS: The novel ESC-nomogram showed good performance for predicting antiviral efficacy in HBeAg-positive CHB patients with NAs treatment.

Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure.

Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Incidence and risk factors related to SARS-CoV-2 infection, reinfection, and seroconversion: Analysis of a healthcare workers cohort from a university hospital in Colombia.

Objectives: To determine the incidence and factors associated with SARS-CoV-2 infection and seroconversion among healthcare workers (HCWs) during the COVID-19 pandemic in a university hospital in Colombia. Methods: We analyzed the CoVIDA-Fundación Santa Fe de Bogotá (FSFB) cohort, consisting of 419 HCWs from the FSFB university hospital. The cohort was followed during active surveillance (June 25, 2020, to April 30, 2021) and passive surveillance (May 01, 2021, to March 16, 2022) periods. Incidence rates for SARS-CoV-2 infection, reinfection, and seroconversion were estimated, considering pre- and post-COVID-19 vaccination. Cox proportional-hazards models were used to identify factors related to infection and seroconversion during the active surveillance period. Results: COVID-19 incidence rate ranged between 16-52 cases per 1000 person-month. SARS-CoV-2 reinfections were rare, ranging between less than one case to 13 cases per 1000 person-month. The seroconversion rates ranged between 52-55 cases per 1000 person-month. High socioeconomic level was a protective factor for SARS-CoV-2 infection, while SARS-CoV-2 infection was the main factor associated with seroconversion. Conclusion: This study provides insights into the incidence and risk factors of SARS-CoV-2 infection among HCWs in a Colombian university hospital. The findings may offer valuable guidance for reducing virus spread within healthcare settings.

Impact of core protein naturally selected mutants associated with HBeAg-negative status in HBV biosynthesis.

Hepatitis B e antigen (HBeAg) loss represents a late stage of chronic hepatitis B virus (HBV) infection associated with a drastic decrease in HBV-DNA, a lower risk of disease progression, and the occurrence of several mutations in the preCore/core region. However, the underlying mechanisms supporting the downregulation of viral replication have yet to be elucidated. In the present study, the analysis of the frequency of subgenotype D1 core protein (HBc) mutations associated with HBeAg status revealed a higher mutation rate in HBeAg-negative sequences compared to HBeAg-positive ones. Particularly, 22 amino acids exhibited a higher frequency of mutation in HBeAg-negative sequences, while the remaining residues showed a high degree of conservation. Subsequently, the assessment of HBc mutants derived from HBeAg-negative patients in viral structure and replicative capacity revealed that HBc mutations have the ability to modulate the subcellular localization of the protein (either when the protein was expressed alone or in the context of viral replication), capsid assembly, and, depending on specific mutation patterns, alter covalently closed circular DNA (cccDNA) recycling and up- or downregulate viral replication. In conclusion, HBc mutations associated with HBeAg-negative status impact on various stages of the HBV life cycle modulating viral replication during the HBeAg-negative stage of infection.

No seroconversion among healthcare workers exposed to SARS-CoV-2 during the early phase of the pandemic / Ausencia de seroconversión en trabajadores de la salud expuestos a SARS-CoV-2 durante la primera fase de la pandemia

BACKGROUND: The SARS-CoV-2 pandemic is associated with morbidity, hospitalizations, absenteeism, and mortality among healthcare workers (HCW). AIM: To evaluate the seroconversion rate in HCW exposed to SARS-CoV-2 in the early pandemic phase in 2020 at a regional reference hospital. MATERIAL AND METHODS: One hundred seventy-nine HCW working at a regional hospital were invited to a longitudinal study performed between April-July 2020. A serological analysis by ELISA IgG for viral nucleoprotein and protein S with a secondary analysis by ELISA IgG protein S1/S2 for samples with positive or doubtful result was carried out together with a complementary online survey to inquire about occupational or community exposures to SARS-CoV-2. RESULTS: Two cases with baseline infection were detected (1.1%, one symptomatic and one asymptomatic) and no cases of seroconversion were detected. During the study period, there were 136 patients hospitalized with COVID-19, and regional weekly COVID-19 incidence ranged from 2.7 to 24.4 per 100,000 inhabitants. No SARS-CoV-2 cases were detected by PCR among 27 HCW who consulted for respiratory symptoms in the period. Online surveys confirmed direct care of COVID-19 patients and also detected a high degree of unprotected social interaction at work. CONCLUSIONS: There was no evidence of seroconversion in this group of HCW exposed to the risk of infection by SARS-CoV-2 during the onset of the COVID-19 pandemic. Personal protective equipment and other measures used by the HCW were extremely useful for their protection in the initial phase of the pandemic.

ANTECEDENTES: La pandemia de SARS-CoV-2 está asociada a morbilidad, hospitalizaciones, ausentismo y mortalidad entre el personal de salud (PS). OBJETIVO: Evaluar la tasa de seroconversión en el PS expuesto al SARS-CoV-2 en la fase pandémica inicial el 2020 en un hospital regional de referencia. MATERIAL Y MÉTODOS: Ciento setenta y nueve trabajadores de la salud fueron invitados a un estudio longitudinal realizado entre abril-julio de 2020. Se efectuó un análisis serológico por ELISA IgG para nucleoproteína viral y proteína S con un análisis secundario por ELISA IgG proteína S1 / S2 para muestras con resultado positivo o dudoso junto a encuestas complementarias en línea para preguntar sobre exposiciones ocupacionales o comunitarias al SARS-CoV-2. RESULTADOS: Se detectaron dos casos con infección basal (1,1%, uno sintomático y uno asintomático) sin casos de seroconversión. Durante el período de estudio, hubo 136 pacientes hospitalizados con COVID-19, y la incidencia semanal regional de COVID-19 osciló entre 2,7 y 24,4 por 100.000 habitantes. No se detectaron casos de SARS-CoV-2 por PCR entre los 27 funcionarios que consultaron por síntomas respiratorios en este período. Las encuestas en línea confirmaron la atención directa de los pacientes con COVID-19 y también detectaron un alto grado de interacción social desprotegida en el trabajo. CONCLUSIONES: No hubo evidencia de seroconversión en un grupo de funcionarios expuestos al riesgo de infección por SARS-CoV-2 durante el inicio de la pandemia de COVID-19. Los equipos de protección personal y otras medidas utilizadas por el PS fueron de suma utilidad para su protección en la fase inicial de la pandemia.

Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure

Abstract Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Seroconversión posterior a la aplicación de vacuna Pfizer anticovid-19 en personal de la salud / Seroconversión rates following covid-19 Pfizer vaccine application among health personnel

Introducción: la pandemia por COVID-19 constituyó un problema de salud que requirió la realización de esfuerzos sin precedentes para la fabricación de vacunas en tiempo récord. Dada la emergencia no se podían llevar a cabo los protocolos establecidos que componen la fármacovigilancia, razón por la cual es importante realizar estudios locales que contribuyan al conocimiento y vigilancia clínica y farmacológica. Objetivos: evaluar los niveles de anticuerpos desarrollados en quienes recibieron la vacuna Pfizer, determinar los efectos secundarios más frecuentes y describir la mortalidad por todas las causas a un año en este grupo. Métodos: estudio prospectivo, de corte transversal de una cohorte de 105 pacientes, se realizó estadística descriptiva en el análisis univariado y bivariado para los niveles de anticuerpos, se describe la correlación de la edad con los niveles de anticuerpos y la mortalidad cruda de los pacientes a 1 año. Resultados: la edad media de los 105 pacientes fue 36,45 años (DE 10,11), con tendencia al aumento de los niveles de anticuerpos en la segunda toma y descenso en la tercera; se encontró una correlación negativa significativa entre edad y niveles de anticuerpos en la segunda toma. Conclusiones: en los sujetos más jóvenes se presentaron mayores títulos de anticuerpos que disminuyeron con el tiempo, la variabilidad en la titulación puede depender de varios factores como edad, género, imnunosupresores y comorbilidades. Es necesaria la medición para realizar una vacunación periódica e individualizarla. La mortalidad a un año fue de 0%.

Introduction: the COVID-19 pandemic prompted unprecedented efforts to manufacture vaccines in record time. Given the emergency, to conduct the established pharmacovigilance protocols was not possible, thus, the importance of carrying out local studies which contribute to gain understanding and clinical and pharmacological surveillance. Objectives: to evaluate antibody levels developed in subjects who received the Pfizer vaccine; to determine the most frequent side effects; and describe all-cause 1-year mortality in this group. Methods: a prospective, cross-sectional study in a cohort of 105 patients. Descriptive statistics were conducted by univariate and bivariate analyses of antibody levels. The correlation between age and antibody levels and the crude 1-year mortality rate among patients is described. Results: mean age was 36.45 years (SD 10.11), with a tendency for antibody levels to increase with the second dose and decrease with the third dose. A significant negative correlation was found between age and antibody levels in the second dose. Conclusions: younger subjects had higher antibody titers, which decreased over time. The variability of titer estimates may depend on several factors such as, age, gender, immunosuppressive therapies and comorbidities. Measurements are essential for periodic and individualized vaccination. One-year mortality rate was 0%.

Immunogenicity profile after COVID-19 vaccination in patients with onco-hematological diseases

ABSTRACT Objective To evaluate the influence of onco-hematological pathologies on seroconversion to COVID-19 vaccines, in addition to the effects of chemotherapy treatment on this response. Methods The present study evaluated the immunogenic response of 76 patients with onco-hematological diseases to multiple vaccine platforms compared to 25 control individuals. Results Our results showed positive response rates of 74.02% in patients with onco-hematological diseases and 100% in controls. When analyzed according to etiological group, patients with lymphoproliferative disorders achieved a positive vaccine response rate of 58.7%, whereas those with myeloproliferative diseases achieved a 100% response rate. We also observed that patients previously exposed to COVID-19 presented a 75% increase in their antibody values after vaccination, and these values were 37% higher than those of patients who did not have such exposure. We found that patients who underwent B-lymphocyte-depleting therapy in the last 2 years before vaccination had a worse response rate of 18.75%. Conclusion Despite the immunosuppression of patients with onco-hematological diseases, caused by the biology of their diseases and treatment, benefit and safety in vaccinating these patients are observed, in view of the important recall immune response and incidence of adverse effects similar to those of the healthy population.

The long-term dynamics of serum antibodies against SARS-CoV-2.

Objective: To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response. Methods: Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Results: Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17-39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Conclusions: Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.

Analysis of Viral and Host Factors on Immunogenicity of 2018, 2019, and 2020 Southern Hemisphere Seasonal Trivalent Inactivated Influenza Vaccine in Adults in Brazil.

Annual vaccination against influenza is the best tool to prevent deaths and hospitalizations. Regular updates of trivalent inactivated influenza vaccines (TIV) are necessary due to high mutation rates in influenza viruses. TIV effectiveness is affected by antigenic mismatches, age, previous immunity, and other host factors. Studying TIV effectiveness annually in different populations is critical. The serological responses to Southern-Hemisphere TIV and circulating influenza strains were evaluated in 2018−2020 among Brazilian volunteers, using hemagglutination inhibition (HI) assays. Post-vaccination titers were corrected to account for pre-vaccination titers. Our population achieved >83% post-vaccination seroprotection levels, whereas seroconversion rates ranged from 10% to 46%. TIV significantly enhanced antibody titers and seroprotection against all prior and contemporary vaccine and circulating strains tested. Strong cross-reactive responses were detected, especially between H1N1 subtypes. A/Singapore/INFIMH-16-0019/2016, included in the 2018 TIV, induced the poorest response. Significant titer and seroprotection reductions were observed 6 and 12 months after vaccination. Age had a slight effect on TIV response, whereas previous vaccination was associated with lower seroconversion rates and titers. Despite this, TIV induced high seroprotection for all strains, in all groups. Regular TIV evaluations, based on regional influenza strain circulation, should be conducted and the factors affecting response studied.

Analysis of immunization time, amplitude, and adverse events of seven different vaccines against SARS-CoV-2 across four different countries.

Background: Scarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI. Methods: A multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed. Results: We recruited 1867 individuals [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p<0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p<0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with previous SARS-CoV-2 infection, Gam-COVID-Vac and ChAdOx1-S (p<0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naïve SARS-CoV-2 subjects with age and sex (p<0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p<0.01). mRNA-1273 had the highest number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p<0.001). Conclusions: The magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response only correlates with AEs in patients previously exposed to SARS-CoV-2. Registration number: ClinicalTrials.gov, identifier NCT05228912.

Dynamics of the Immune Response in Hospitalized SARS-CoV-2-infected Cancer Patients.

Seroconversion rates were compared between oncological and nononcological patients infected with SARS-CoV-2 during a 14-day hospitalization time. All COVID-19 non-oncological and solid malignancies patients reached 100% seroconversion at day 14, while less than half of the hematological patients were seroconverted at the same time point. Despite the limited number and variability of the patient's cohort, we conclude that there is a delayed seroconversion in the hematological malignancies group, which may be linked to changes in the hematological parameters, immune suppression and/or oncological treatments that are typically associated with these patients.

Risk factors for seroconversion of HIV among children exposed in the State of Santa Catarina, 2007-2017 / Fatores de risco para a soroconversão de crianças expostas ao HIV no Estado de Santa Catarina, 2007-2017

Abstract Objectives: to estimate the proportion of seroconversion cases among infants exposed to HIV and verify the risk factors associated. Methods: this was a historical cohort study conducted in the State of Santa Catarina between 2007 and 2017. The data were obtained from the Notifable Diseases Information System (SINAN - Portuguese acronym) that records HIV-infected pregnant women and HIV-exposed infants. The public health service monitored the infants from birth to 18 months of age to determine whether HIV seroconversion occurred. Results: a total of 5,554 HIV-infected pregnant women were included in the study (mean age 26.7±6.5 years). They were predominantly white, with poor education level, and were diagnosed with HIV until the 2nd trimester of pregnancy. A total of 4,559 records of HIV-exposed infants were screened, of which 130 cases (2.9%) of seroconversion were confrmed. Non-use of antiretroviral drugs during pregnancy (OR=9.31, CI95%=5.97-14.52; p<0.001) and breastfeeding (OR=3.10, CI95%=1.34-7.20; p=0.008) were independent risk factors for seroconversion. Conclusions: these data demonstrate gaps in prenatal care, regarding adherence to treatment and monitoring of HIV-infected mothers, resulting in new cases of HIV among children, which could be avoided.

Resumo Objetivos: estimar a proporção de soroconversão da criança exposta ao HIV e verificar os fatores de risco associados, no período de 2007-2017 em Santa Catarina. Métodos: o delineamento utilizado foi de coorte histórica e os dados obtidos no Sistema de Informação de Agravos de Notificação (SINAN) que registra as gestantes infectadas e as crianças expostas ao HIV. As crianças foram acompanhadas pelo serviço de saúde desde o nascimento até o 18º mês de vida, para determinar a ocorrência de soroconversão pelo HIV. Resultados: foram identificadas 5.554 gestantes infectadas pelo HIV com média de idade de 26,7±6,5 anos, predomínio da raça branca, baixa escolaridade e que receberam o diagnóstico para o HIV até o 2º trimestre gestacional. Foram incluídas 4.559 fichas de crianças expostas ao HIV, das quais 130 casos (2,9%) de soroconversão foram confrmados. O não uso de antirretroviral durante a gestação (OR=9,31, IC95%=5,97-14,52; p<0,001) e aleitamento materno (OR=3,10, IC95%=1,34-7,20; p=0,008) foram fatores de risco independentes para a soroconversão. Conclusões: esses dados demonstram lacunas na assistência pré-natal, quanto a adesão ao tratamento e acompanhamento de mães infectadas pelo HIV, resultando em casos novos de HIV entre crianças, que poderiam ser evitados.

Metodología de investigación en farmacogenética: estudios de casos y controles / Methodology for research in pharmacogenetics: Case-control studies

RESUMEN La farmacogenética estudia la asociación entre el fenotipo farmacológico de un individuo con su constitución genética, y el diseño de estudios de casos y controles es una metodología de uso frecuente. Este diseño consiste en que se analiza la frecuencia de las variantes genéticas en los casos, es decir, de los pacientes que presentan el fenotipo (desenlaces o resultados) comparado con los controles. Para obtener una calidad metodológica adecuada en este tipo de estudios es importante trabajar con fenotipos precisos, adecuada selección de los casos y controles y tamaño de la muestra; seleccionar una metodología adecuada para la identificación de variantes genéticas; y en el momento del análisis de resultados utilizar el Equilibrio de Hardy-Weinberg (EHW) e interpretar los resultados considerando la posibilidad de un fenómeno de fenoconversión.

ABSTRACT Pharmacogenetics studies the association between the pharmacological phenotype of an individual with his/her genetic constitution. Case-control studies is a commonly used methodology when performing pharmacogenetics research. This design analyses the frequency of genetic variants in cases; that is, of those patients who have a particular phenotype (outcomes or results) compared with controls. For obtaining adequate methodological quality in pharmacogenetic case-control studies, it is important to work with precise phenotypes, have adequate case and control selection and appropriate sample size; select an adequate methodology for the identification of genetic variants, analyze the results using Hardy-Weinberg Equilibrium (HWE); and interpret the results considering the possibility of a phenoconversion phenomenon.

Detection of anti-Histoplasma capsulatum antibodies and seroconversion patterns in critically ill patients with COVID-19: An underdiagnosed fungal entity complicating COVID-19?

The patients with severe COVID-19 are at increased risk for invasive fungal infections, such as invasive pulmonary aspergillosis and candidiasis, which increase morbidity and mortality. However, clinicians should also consider the possibility of reactivating latent Histoplasma capsulatum in patients with severe COVID-19 living within areas of endemicity who have worsening respiratory function or sepsis, even if they do not have classical risk factors for histoplasmosis (e.g., HIV/AIDS). Bearing in mind this scenario, serum samples of 39 non-HIV/AIDS patients from Buenos Aires hospitalized due to severe COVID-19 pneumonia were analyzed for anti-H. capsulatum-specific IgG antibodies by an in-house ELISA. Antibodies against H. capsulatum were detected in the sera of 8/39 patients (20.51%). To exclude the possibility that these antibodies arose from past exposure of these patients to the fungus, paired serum samples obtained after an interval of at least 10 days were evaluated. Of them, five patients (62.5%) with negative anti-H. capsulatum antibodies at baseline became seropositive 7-10 days later. Three patients (37.5%) had positive anti-H. capsulatum antibodies at baseline, but at time point 2, one of them became seronegative and the other one diminished the antibody titers (4000 vs. 16000 at baseline). The remaining patients displayed higher antibody titers at time point 2 (4000 vs. 1000 at baseline) and died immediately thereafter. In conclusion, awareness of the possibility of fungal co-infections is essential to reduce delays in diagnosis and treatment in order to help prevent severe illness and death from these infections. LAY SUMMARY: This study verifies that patients with severe COVID-19 at ICU are at risk for histoplasmosis reactivation in endemic areas. Accurate diagnosis of this deadly fungal disease among critically ill patients with COVID-19 living in endemic areas for histoplasmosis is needed.