Timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.

OBJECTIVES: To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort. METHODS: Infants (N = 444) were enrolled at 10-14 days of life and observed weekly until 2 years of age. Stool samples were collected for each acute gastroenteritis (AGE) episode, and routine stool samples were collected monthly. Stool samples were tested for sapovirus using RT-qPCR, and positive samples were genotyped. RESULTS: A total of 348 children completed 2 years of AGE weekly surveillance; 93 (26.7%) of them experienced sapovirus AGE. Most infections occurred after 5 months of age and mainly during the second year of life (62.4%, 58/93) and early in the rainy season. Sapovirus screening in all stools from a subset of 67 children who consistently provided samples showed sapovirus infections in 91 of 330 (27.6%) AGE episodes and in 39 of 1350 (2.9%) routine stools. In this subset, the median age at the first sapovirus AGE was 11.2 months (95% CI, 9.3-15.9 months); 38 of 67 (57%) children experienced re-infections, 19 symptomatic and 19 asymptomatic. On average, sapovirus re-infections were reported 7.2 months after symptomatic and 5.3 months after asymptomatic infections. Genogroup GI (64%, 69/108) was the most common detected. Sapovirus GI.1 was more frequently detected in AGE stool samples than in routine stool samples (47.2%, 43/91 vs. 25.6%, 10/39; p 0.005), and re-infection with the same genotype was uncommon. DISCUSSION: The first sapovirus infections occurred at approximately 11 months of age, whereas the median time to symptomatic re-infection was 7.2 months. Re-infections with the same sapovirus genotype were rare during 2 years of life suggesting genotype-specific protection after natural infection.

Novel SARS-CoV-2 variants: the pandemics within the pandemic.

BACKGROUND: Many new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been termed variants of concern/interest (VOC/I) because of the greater risk they pose due to possible enhanced transmissibility and/or severity, immune escape, diagnostic and/or treatment failure, and reduced vaccine efficacy. AIMS: We sought to review the current knowledge of emerging SARS-CoV-2 variants, particularly those deemed VOC/Is: B.1.351, B.1.1.7, and P.1. SOURCES: MEDLINE and BioRxiv databases, as well as the grey literature, were searched for reports of SARS-CoV-2 variants since November 2020. Relevant articles and their references were screened. CONTENT: Mutations on the spike protein in particular may affect both affinity for the SARS-CoV-2 cell receptor ACEII and antibody binding. These VOC/Is often share similar mutation sets. The N501Y mutation is shared by the three main VOCs: B.1.1.7, first identified in the United Kingdom, P.1, originating from Brazil, and B.1.351, first described in South Africa. This mutation likely increases transmissibility by increasing affinity for ACEII. The B.1.351 and P.1 variants also display the E484K mutation which decreases binding of neutralizing antibodies, leading to partial immune escape; this favours reinfections, and decreases the in vitro efficacy of some antibody therapies or vaccines. Those mutations may also have phenotypical repercussions of greater severity. Furthermore, the accumulation of mutations poses a diagnostic risk (lowered when using multiplex assays), as seen for some assays targeting the S gene. With ongoing surveillance, many new VOC/Is have been identified. The emergence of the E484K mutation independently in different parts of the globe may reflect the adaptation of SARS-CoV-2 to humans against a background of increasing immunity. IMPLICATIONS: These VOC/Is are increasing in frequency globally and pose challenges to any herd immunity approach to managing the pandemic. While vaccination is ongoing, vaccine updates may be prudent. The virus continues to adapt to transmission in humans, and further divergence from the initial Wuhan sequences is expected.

Distinguishing SARS-CoV-2 bonafide re-infection from pre-existing minor variant reactivation.

Different groups have recently reported events of SARS-CoV-2 reinfection, where patients had a sequence of positive-negative-positive RT-PCR tests. However, such events could be explained by different scenarios such as intermittent viral shedding, bonafide re-infection or multiple infection with alternating predominance of different viruses. Analysis of minor variants is an important tool to distinguish between these scenarios. Using ARTIC network PCR amplification and next-generation sequencing, we obtained SARS-CoV-2 sequences from two timepoints (with a time span of 102 days) of a patient followed at the Brazilian National Cancer Institute. Within-host variant analysis evidenced three single nucleotide variants (SNVs) at the consensus viral sequence in the second timepoint that were already present in the first timepoint as minor variants. Another five SNVs found in the second timepoint were not detected in the first sample sequenced, suggesting an additional infection by a yet another new virus. Our observation shed light into the existence of different viral populations that are present in dynamic frequencies and fluctuate during the course of SARS-CoV-2 infection. The detection of these variants in distinct disease events of an individual highlights a complex interplay between viral reactivation from a pre-existing minority variant and reinfection by a different virus.

Contribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus.

The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.

Toxoplasma gondii: A study of oocyst re-shedding in domestic cats.

The aim of the present study was to evaluate the re-shedding of T. gondii oocysts in cats fed tissue cysts of homologous and heterologous strains 12, 24 and 36 months after the first infection. Thirteen cats were used in the present study and were divided into four groups: G1 (n=2), G2 (n=3), G3 (n=5), and G4 (n=3). G1, G3 and G4 cats were infected with brain cysts of ME49 and G2 with TgDoveBr8, both genotype II strains of T. gondii. The G1 and G2 cats were re-infected after twelve months with brain cysts of VEG strain (genotype III), and G3 cats were re-infected with TgDoveBr1 (genotype II). The G3 cats were re-infected a third time after 24 months from the second infection, and the G4 cats were re-infected 36 months after the initial infection with cysts of the VEG strain. The cats' feces were evaluated using fecal flotation and genotyped with PCR-RFLP. The serological responses for IgM, IgA and IgG were determined by ELISA. All cats shed oocysts after the initial infection. Only one G1 cat shed oocysts when re-infected after twelve months with the VEG strain. No G2 cats excreted oocysts after the second infection with VEG. G3 cats, when re-infected after twelve months with the TgDoveBr1 strain, did not shed oocysts. However, when challenged after a third time with the VEG strain, three out of four cats shed oocysts. In the G4 group, when re-infected after thirty-six months with the VEG strain, two out of three cats shed oocysts. All oocyst samples were genotyped and characterized as the same genotype from the inoculum. Protection against oocyst re-excretion occurred in 90%, 25%, and 33.4% of cats after 12, 24, and 36 months from the initial infection, respectively. Therefore, the environmental contamination by oocysts from re-infected adult cats is only 30% lower than from kittens. In conclusion, the excretion of T. gondii oocysts was higher in experimentally re-infected cats throughout the years, especially when a heterologous strain was used.

Ranging behavior drives parasite richness: A more parsimonious hypothesis.

Parasitism is a ubiquitous interspecific interaction that may play an important role in the evolution of hosts and parasites, molding many aspects of their behavior and ecology. Detecting behavioral changes of hosts infected with parasites is not a straightforward task. Extrapolating from individual-level responses to group-level decision-making is still a much more complex challenge. The ranging behavior of hosts that live in social groups is a good example. Many hypotheses of the cause-effect relationship between this behavior and parasite diversity and load have been proposed. For instance, Brockmeyer et al. [2015, Am. J. Primatol. 77:1036-1048] recently suggested that the richness of protozoan parasites influences the daily path length of free-ranging mandrills. We believe that this explanation for the relationship contains several implicit assumptions. Therefore, we offer an alternative, more parsimonious hypothesis in which daily path length is the driver of parasite richness rather than its consequence. Our hypothesis only assumes that ranging farther exposes animals to a richer parasite diversity. We discuss the data required to test these alternative hypotheses and recall empirical evidence and theoretical modeling results supporting or rejecting their assumptions. We also propose a model of the expected outcomes in terms of species richness, load, intensity of infection, and within-group community similarity of non-lethal environmentally transmitted parasites in social animal groups showing distinct patterns of range use. Am. J. Primatol. 78:923-927, 2016. © 2016 Wiley Periodicals, Inc.

Clinical and Immunological Benefits of OM-85 Bacterial Lysate in Patients with Allergic Rhinitis, Asthma, and COPD and Recurrent Respiratory Infections.

PURPOSE: The aim of this study was to evaluate the efficacy of OM-85 in reducing the incidence of respiratory tract infections (RTIs) in patients with allergic rhinitis, asthma, or chronic obstructive pulmonary disease (COPD), and its effect on immunological parameters, namely serum and secretory IgA levels. METHODS: This was an open-label, prospective, sequential study which included 84 consecutive patients aged 16-65 years, who presented with recurrent (three or more) respiratory infections during the year prior to study entry. In the first year of the study, patients received standard optimized care (SOC), according to their underlying disease condition (asthma, allergic rhinitis, or COPD). In the following year, patients received treatment with OM-85 oral bacterial lysate (one 7 mg capsule daily for ten consecutive days per month, for 3 months), with a 6-month follow-up. Medical history, clinical symptoms, serum, and secretory IgA levels, and the number of infections and exacerbations were evaluated before and after treatment. RESULTS: There was a decrease in the total number of RTIs before the OM-85 treatment period (SOC only) compared to the year before the study start [69/266 (corresponding to a 74 % reduction)] and an additional decrease [38/69 (corresponding to a 45 % reduction)] after OM-85 treatment; p < 0.05. There was also a significant reduction in the total number of exacerbations related to the patients' underlying medical conditions, which decreased from 55 to 35 during OM-85 (+SOC) treatment, corresponding to a reduction of 36 %. In addition, an increase in serum and secretory IgA levels which coincided with the administration of OM-85 was observed. CONCLUSIONS: Our results showed the clinical benefits of OM-85 in reducing RTIs and exacerbations of the underlying medical condition, in patients with allergic rhinitis, asthma, or COPD.

Primoinfección por Trypanosoma cruzi previene re-infecciones severas en ratones / Trypanosoma cruzi primary infection prevents severe re-infection in mice

The effect of Trypanosoma cruzi re-inoculations on experimentally infected mice was evaluated. Mice received a primary infection by intradermal inoculation of 5x103 T. cruzi metacyclic infective forms from laboratory infected Rhodnius prolixus. From 200 mice initially infected, 52 survived the course of the infection during 23 weeks. From these, 45 mice were re-inoculated and seven used as infected control. Two re-inoculations were performed using the same conditions as in the prime-infection. Observations on re-inoculated mice revealed a parasitemia level lower than that detected during the primary-infection. Serologic evaluation showed no variation in the immunoglobulin profile, maintaining similar IgM and IgG levels after re-inoculations. Similar mortality rates were observed in primary-infected, re-inoculated and infected control mice. No remarkable histopathological changes attributable to re-inoculation were detected. These results lead us to conclude that T. cruzi re-inoculation in mice previously infected with the same parasite does not produce a reactivation of infection similar to the typical acute clinical or immunological profiles. This also suggests that T. cruzi primary infection may prevent severe re-infection, establishing a protective stage making infected mice resistant to a second infection. Epidemiological implications of the present findings are discussed.

Se evalúa el efecto de reinoculaciones por Trypanosoma cruzi en ratones experimentalmente infectados. De un total de 200 ratones que fueron infectados por vía intradérmica con un inóculo de 5x103 tripomastigotes metacíclicos provenientes de especimenes de Rhodnius prolixus, 52 sobrevivieron a la primo-infección luego de 23 semanas. De estos 45 fueron re-inoculados en la misma forma como en la infección primaria y siete fueron utilizados como controles infectados no re-inoculados. Observaciones sistemáticas llevadas a cabo en muestras de los ratones re-inoculados revelaron parasitemias significativamente menores que las detectadas durante la primo-infección. La evaluación serológica no mostró diferencias en los niveles de IgM e IgG entre ratones primo-infectados y los re-inoculados. Observaciones histopatológicas no mostraron cambios atribuibles al efecto de las re-inoculaciones en muestras de corazón y músculo esquelético. Una tasa similar de mortalidad fue observada en ratones primo-infectados, re-inoculados y controles infectados. Se concluye que re-inoculaciones con T. cruzi en ratones previamente infectados con el mismo parásito no producen reactivación de la infección similar al típico cuadro agudo. Asimismo, se sugiere que la primo-infección por T. cruzi previene una reinfección severa estableciendo un estado de protección y resistencia a subsecuentes infecciones. Se discuten las implicaciones epidemiológicas de los presentes hallazgos.