Refractoriness of Eryptotic Red Blood Cells to Plasmodium falciparum Infection: A Putative Host Defense Mechanism Limiting Parasitaemia

Recently, we have described that apoptosis-like process of red blood cells (RBC) – eryptosis – in malaria is not restricted to parasitized cells, occurring also in non-parasitized RBC (nRBC). Besides to pathogenic proprieties, apoptosis also participates in the innate defense trough restriction of intracellular pathogens propagation. In the present study, we investigated the capacity of P. falciparum parasites to infect eryptotic RBC. Schizont parasitized RBC concentrated by magnetic separation were cultured with eryptotic RBC obtained by ionomycin treatment and, then, parasite growth was evaluated in Giemsa-stained thin blood smears. While parasites infected and developed normally in control non-eryptotic RBC, cultures performed with eryptotic RBC had a marked decrease in parasitaemia. It was noteworthy a great number of free merozoites in eryptotic RBC cultures, indicating that these cells were not susceptible to invasion. We suggest that although eryptosis could be involved in malaria pathogenesis, it could also acting protectively by controlling parasite propagation

Immune system challenge improves recognition memory and reverses malaria-induced cognitive impairment in mice

The immune system plays a role in the maintenance of healthy neurocognitive function. Different patterns of immune response triggered by distinct stimuli may affect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the effect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria. We show that immune modulation induced by a specific combination of immune stimuli that induce a type 2 immune response can enhance long-term recognition memory in healthy adult mice subjected to novel object recognition task (NORT) and reverse a lack of recognition ability in NORT and anxiety-like behaviour in a light/dark task that result from a single episode of mild Plasmodium berghei ANKA malaria. Our findings suggest a potential use of immunogens for boosting and recovering recognition memory that may be impaired by chronic and infectious diseases and by the effects of ageing

Malaria in Brazil: an overview

Malaria is still a major public health problem in Brazil, with approximately 306 000 registered cases in 2009, but it is estimated that in the early 1940s, around six million cases of malaria occurred each year. As a result of the fight against the disease, the number of malaria cases decreased over the years and the smallest numbers of cases to-date were recorded in the 1960s. From the mid-1960s onwards, Brazil underwent a rapid and disorganized settlement process in the Amazon and this migratory movement led to a progressive increase in the number of reported cases. Although the main mosquito vector (Anopheles darlingi) is present in about 80% of the country, currently the incidence of malaria in Brazil is almost exclusively (99,8% of the cases) restricted to the region of the Amazon Basin, where a number of combined factors favors disease transmission and impair the use of standard control procedures. Plasmodium vivax accounts for 83,7% of registered cases, while Plasmodium falciparum is responsible for 16,3% and Plasmodium malariae is seldom observed. Although vivax malaria is thought to cause little mortality, compared to falciparum malaria, it accounts for much of the morbidity and for huge burdens on the prosperity of endemic communities. However, in the last few years a pattern of unusual clinical complications with fatal cases associated with P. vivax have been reported in Brazil and this is a matter of concern for Brazilian malariologists. In addition, the emergence of P. vivax strains resistant to chloroquine in some reports needs to be further investigated. In contrast, asymptomatic infection by P. falciparum and P. vivax has been detected in epidemiological studies in the states of Rondonia and Amazonas, indicating probably a pattern of clinical immunity in both autochthonous and migrant populations. Seropidemiological studies investigating the type of immune responses elicited in naturally-exposed populations to several malaria vaccine candidates in Brazilian populations have also been providing important information on whether immune responses specific to these antigens are generated in natural infections and their immunogenic potential as vaccine candidates. The present difficulties in reducing economic and social risk factors that determine the incidence of malaria in the Amazon Region render impracticable its elimination in the region. As a result, a malaria-integrated control effort - as a joint action on the part of the government and the population - directed towards the elimination or reduction of the risks of death or illness, is the direction adopted by the Brazilian government in the fight against the disease

Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESThe absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventi903464472CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESSEM INFORMAÇÃOSEM INFORMAÇÃOSEM INFORMAÇÃOThe authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES (CAPES) for financial suppor

A syndemic perspective

Funding Information: Paula Saraiva for the support with bibliography. Funda??o para a Ci?ncia e Tecnologia for funds to GHTM UID/04413/2020. CTDR is supported by CNPq, Brazil, through a Productivity Research Fellowship and is a ?Cientista do Nosso Estado? by Faperj, Rio de Janeiro, Brazil. Funding Information: Paula Saraiva for the support with bibliography. Fundação para a Ciência e Tecnologia for funds to GHTM UID/04413/2020 . CTDR is supported by CNPq , Brazil, through a Productivity Research Fellowship and is a “Cientista do Nosso Estado” by Faperj, Rio de Janeiro, Brazil. Publisher Copyright: © 2021 The AuthorsThe SARS-CoV-2 pandemic has affected communities, populations, and countries throughout the world. As the SARS-CoV-2 pandemic developed, the extent to which the disease interacted with already existing endemic, non-communicable and infectious diseases became evident, hence deeply influencing health outcomes. Additionally, a synergistic effect has been demonstrated also with socio-economic, cultural, and contextual determinants of health which seem to contribute to poorer health and accumulating social disadvantages. In this essay, using as a starting point the syndemic theory that translates the cumulative and intertwined factors between different epidemics, we argue that the SARS-CoV-2 is a one health issue of a syndemic nature and that the failure to acknowledge this contributes to weakened policy-making processes and public health responses and ineffective health policies and programs.publishersversionpublishe

Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in Brazil: consequences on disease morbidity and control

In Brazil, malaria still remains a clinically important febrile syndrome for local populations and travelers, occurring mostly in the Amazon Basin. This review aims to report the main efforts employed to control this disease since the 1940s and the emergence of Plasmodium falciparum and Plasmodium vivax chemoresistance to chloroquine and sulphadoxine-pyrimethamine among other drugs. Additionally, in vivo, in vitro and molecular studies as well as malaria chemoresistance consequences on disease morbidity and policy treatment guidelines were commented

Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola

Abstract Background Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola. Methods Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes. Results The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples). Conclusion This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola

Finding connections in the unexpected detection of Plasmodium vivax and Plasmodium falciparum DNA in asymptomatic blood donors: a fact in the Atlantic Forest

Abstract\ud A recent paper in Malaria Journal reported the observation of unexpected prevalence rates of healthy individuals carrying Plasmodium falciparum (5.14%) or Plasmodium vivax (2.26%) DNA among blood donors from the main transfusion centre in the metropolitan São Paulo, a non-endemic area for malaria. The article has been challenged by a group of authors who argued that the percentages reported were higher than those found in blood banks of the endemic Amazon Region and also that that paper had not considered the literature on the classical dynamics of malaria transmission in the Atlantic Forest, which involves Anopheles (Kerteszia) cruzii and bromeliad malaria, due to P. vivax and Plasmodium malariae parasites, but not P. falciparum. The present commentary paper responds to this challenge and brings evidence and literature data supporting that the observed prevalence ratios may indicate a proportion of individuals that are exposed to Plasmodium transmission in permissive environments; that blood carrying parasite DNA may not be necessarily infective if used in transfusion; and that in the literature, there are examples supporting the circulation of P. falciparum in the area.FAPES

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model

In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice’s splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies