Mental health and COVID-19 in a general population cohort in Spain (COVICAT study).

PURPOSE: Mental health conditions may affect outcome of COVID-19 disease, while exposure to stressors during the pandemic may impact mental health. The purpose of this study was to examine these factors in relation to ocurrence of depression and anxiety after the first outbreak in Spain. METHODS: We contacted 9515 participants from a population-based cohort study in Catalonia between May and October 2020. We drew blood samples to establish infection to the virus. Pre-pandemic mental health conditions were confirmed through Electronic Health Registries. We used the Hospital Anxiety and Depression Scale to assess severe depression and anxiety post-pandemic. Exposure to proximal, financial and wider environment stressors during the lockdown were collected. We calculated Relative Risks (RR), adjusting for individual- and contextual covariates. RESULTS: Pre-pandemic mental health disorders were not associated with SARS-CoV-2 infection , but were associated with severity of COVID-19 disease. People with pre-existing mental health disorders showed higher prevalence of severe depression (25.4%) and anxiety (37.8%) than those without prior mental disorders (4.9% and 10.1%). Living alone was a strong predictor of severe depression among mental health patients (RR = 1.6, 95% CI 1.2-2.2). Among those without prior mental health disorders, post-lockdown depression and anxiety were associated with household interpersonal conflicts (RR = 2.6, 95% CI 2.1-3.1; RR = 2.1, 95% CI 1.9-2.4) and financial instability (RR = 2.2, 95% CI 1.8-2.9; 1.9, 95% CI 1.6-2.2). CONCLUSIONS: The COVID-19 pandemic and the lockdown were associated with increased post-lockdown depression and anxiety. Patients with pre-existing mental health conditions are a vulnerable group for severe COVID-19 disease.

Evaluation of canine leishmaniosis vaccine CaniLeish® under field conditions in native dog populations from an endemic Mediterranean area-A randomized controlled trial.

Dog vaccination is considered an effective way of reducing Leishmania infantum infection incidence in the canine population, as well as its transmission to humans. However, the use of partially effective vaccines can have the detrimental effect of "masking" vaccinated asymptomatic carriers, capable of harbouring the parasite and transmitting it to naïve individuals. After eight years on the European market, few studies have been released on CaniLeish® vaccine safety and efficacy. The present study, a one-year randomized CaniLeish® vaccine field trial, was performed in a canine leishmaniosis endemic area and included animals selected from a native dog population (n = 168). No severe adverse reactions were observed in vaccinated dogs (n = 85). Cases of active L. infantum infection were detected by serological, molecular and clinical follow-up of dogs. One-year post-vaccination, no differences in number or severity of L. infantum active infections were observed between study groups (n = 4 in each group). Vaccine-induced cellular immunity, assessed through interferon-γ quantification, showed significantly higher levels of this cytokine one-month post-vaccination in the vaccine group (p < 0.001), but no differences were observed after nine months between trial groups (p = 0.078). These results fail to support the reported CaniLeish® efficacy in the prevention of active L. infantum infection in dogs from endemic areas and naturally exposed to the parasite.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Massive Plasmodium falciparum visceral sequestration: a cause of maternal death in Africa.

Sequestration of Plasmodium falciparum-infected erythrocytes (PfIE) in the capillaries of the central nervous system (CNS) is the pathognomonic feature of cerebral malaria, a condition frequently leading to death. Sequestration of PfIE in the placental intervillous spaces is the characteristic feature of malaria in pregnancy and is associated with low birthweight and prematurity. Although both patterns of sequestration are thought to result from the expression of different parasite proteins involved in cytoadhesion to human receptors, scant information exists on whether both conditions can coexist and whether this can lead to death. We conducted a prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary-level referral hospital in Maputo, Mozambique, between October 2002 and December 2006. Extensive sampling of all major viscera was performed. All cases showing parasites in any of the viscera were included in the analysis. From 317 complete autopsies PfIEs were identified in ten women (3.2%). All cases showed massive accumulation of PfIE in small capillaries of the CNS but also in most visceral capillaries (heart, lung, kidney, uterus). Placental tissue, available in four cases, showed a massive accumulation of maternal PfIE in the intervillous space. Coma (six women) and dyspnoea (five women) were the most frequent presenting clinical symptoms. In conclusion, massive visceral sequestration of PfIE with significant involvement of the CNS is an infrequent but definite direct cause of maternal death in endemic areas of Africa. The PfIE sequestered in cerebral capillaries and the placenta coexist in these fatal cases.

Identification of minimal CD8+ and CD4+ T cell epitopes in the Plasmodium yoelii hepatocyte erythrocyte protein 17kDa.

Immunization of mice with subunit vaccines based on the Plasmodium yoelii 17kDa hepatocyte erythrocyte protein (PyHEP17), orthologue of Plasmodium falciparum exported protein 1 (PfExp1), induces antigen-specific immune responses and protects against sporozoite challenge. To aid in the characterization of candidate subunit vaccines based on this antigen, we have mapped the immunodominant and subdominant CD8+ and CD4+ T cell epitopes on PyHEP17. Using a panel of 29 15-mer synthetic peptides representing the complete sequence of PyHEP17 (amino acids 1-153), and overlapping each other by 10 residues, we identified an immunogenic region between amino acids 61-85. To define the minimal CD4+ and CD8+ T cell epitopes within this region, we synthesized 25 9-mer peptides overlapping each other by one residue. We screened the capacity of the 15-mer and 9-mer peptides to be recognized by splenocytes and lymph node cells from mice immunized with PyHEP17 plasmid DNA or peptides in Freund's adjuvant, as assessed by cytokine secretion, lymphoproliferation, and cytotoxicity. The profile of response to the T cell epitopes varied depending upon the immunization regimen. Antigen-specific T cell responses were detected to three 15-mer peptides (residues 61-75, 66-80 and 71-85) representing two 10-mer epitopes mapping to residues 66-75 (LTKNKKSLRK) and 71-80 (KSLRKINVAL). IFN-gamma responses after DNA immunization predominantly mapped to two overlapping 9-mer peptides (residues 73-81 and 74-82) sharing an eight amino acid overlap (residues 74-81, RKINVALA), whereas CTL responses predominantly mapped to four 9-mer peptides (residues 61-69, 70-78, 76-84, and 84-92). In addition, a subdominant 10-mer CD8+ T cell epitope recognized by peptide immunization but not DNA immunization mapped to residues 31-40 (GKYGSQNVIK). The identification of these epitopes will allow the evaluation of delivery systems for malaria vaccine candidates as well as the delineation of protective immune mechanisms.

Mutating the anchor residues associated with MHC binding inhibits and deviates CD8+ T cell mediated protective immunity against malaria.

We investigated whether immune responses induced by immunization with plasmid DNA are restricted predominantly to immunodominant CD8+ T cell epitopes, or are raised against a breadth of epitopes including subdominant CD8+ and CD4+ T cell epitopes. Site-directed mutagenesis was used to change one or more primary anchor residues of the immunodominant CD8+ T cell epitope on the Plasmodium yoelii circumsporozoite protein, and in vivo protective efficacy and immune responses against defined PyCSP CD8+ and/or CD4+ epitopes were determined. Mutation of the P2 but not P9 or P10 anchor residues decreased protection and completely abrogated the antigen-specific CD8+ CTL activity and CD8+ dependent IFN-gamma responses to the immunodominant CD8+ epitope and overlapping CD8+/CD4+ epitope. Moreover, mutation deviated the immune response towards a CD4+ T cell IFN-gamma dependent profile, with enhanced lymphoproliferative responses to the immunodominant and subdominant CD4+ epitopes and enhanced antibody responses. Responses to the subdominant CD8+ epitope were not induced. Our data demonstrate that protective immunity induced by PyCSP DNA vaccination is directed predominantly against the single immunodominant CD8+ epitope, and that although responses can be induced against other epitopes, these are mediated by CD4+ T cells and are not capable of conferring optimal protection against challenge.

Differential patterns of human immunoglobulin G subclass responses to distinct regions of a single protein, the merozoite surface protein 1 of Plasmodium falciparum.

Comparisons of immunoglobulin G (IgG) subclass responses to the major polymorphic region and to a conserved region of MSP-1 in three cohorts of African villagers exposed to Plasmodium falciparum revealed that responses to Block 2 are predominantly IgG3 whereas antibodies to MSP-1(19) are mainly IgG1. The striking dominance of IgG3 to Block 2 may explain the short duration of this response and also the requirement for continuous stimulation by malaria infection to maintain clinical immunity.

Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.

Cytoadherence of Plasmodium falciparum-infected erythrocytes to the microvascular endothelium is believed to be a key factor in the development of cerebral malaria. Erythrocyte rosette formation has been correlated with malaria severity in studies from east and west Africa. We cultured fresh isolates from Malawian children with severe (n = 76) or uncomplicated (n = 79) malaria to pigmented trophozoite stage and examined rosette formation and adherence to CD36, intercellular adhesion molecule-1 (ICAM-1), chondroitin sulfate A (CSA), and thrombomodulin (TM). Most (126 of 148) isolates bound to CD36, and 76 of 136 bound to ICAM-1. Fewer bound to CSA (40 of 148) or TM (23 of 148). After controlling for parasitemia, there was an inverse association between binding to CD36 (P = 0.004) or ICAM-1 (P = 0.001) and disease severity. Parasites from children with severe malaria anemia bound least to CD36, whereas ICAM-1 binding was lowest in children with cerebral malaria. There was no difference in rosette formation between any of the groups. In Malawian children, there was no evidence of a positive association between adherence to any of the receptors examined and disease severity. The negative association found raises the possibility that adherence to certain receptors could instead be an indicator of a less pathogenic infection.

Identification of blood meals of Phlebotomus perniciosus (Diptera: Psychodidae) in Spain by a competitive enzyme-linked immunosorbent assay biotin/avidin method.

Blood meals from Phlebotomus perniciosus Newstead, collected in four different places in Spain, were identified to determine host-selection patterns. Blood meals were tested using a competitive enzyme-linked immunosorbent assay (ELISA) biotin-avidin method. Results indicate that this species is an opportunist that feeds on those animals to which it has easiest access. However, some preferences were indicated, because the insect never fed on chickens and frequently fed on sheep at sites where both sheep and goats were present. At some sites, the number of sand flies feeding on dogs was higher than expected, based on the proportion of dogs to man. Nevertheless, differences in host behavior, dispersal of engorged sand flies, and their exo- or endophilic habits make it difficult to assign specific host preferences.