Antimalarial and Cytotoxic Activity of Native Plants Used in Cabo Verde Traditional Medicine.

Medicinal plants have historically been a source of drugs in multiple applications, including the treatment of malaria infections. The Cabo Verde archipelago harbors a rich diversity of native plants, most of which are used for medicinal purposes. The present study investigated the in vitro antiplasmodial activities of four native plants from Cabo Verde (i.e., Artemisia gorgonum, Lavandula rotundifolia, Sideroxylon marginatum, and Tamarix senegalensis). Traditional preparations of these medicinal plants, namely aqueous extracts (infusions) and ethanolic extracts, were tested against both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains using the SYBR Green detection method. The in vitro cytotoxicity was evaluated in Caco-2 and PLP2 cells using a sulforhodamine B colorimetric assay. An ethanolic extract of A. gorgonum and infusions of T. senegalensis exhibited high antiplasmodial activities (EC50 < 5 µg/mL) without cytotoxicity (GI50 > 400 µg/mL). Extracts of L. rotundifolia and S. marginatum exhibited moderate activities, with EC50 values ranging from 10-30 µg/mL. The A. gorgonum ethanolic extract showed activity toward early ring stages, and parasites treated with the T. senegalensis infusions progressed to the early trophozoite stage, although did not develop further to the late trophozoite or schizont stages. Antimalarial activities and the lack of cytotoxicity of the extracts are reported in the present study and support previous claims by traditional practitioners for the use of these plants against malaria while suggesting their ethnopharmacological usefulness as future antimalarials.

Oral polio revaccination is associated with changes in gut and upper respiratory microbiomes of infants.

After the eradication of polio infection, the plan is to phase-out the live-attenuated oral polio vaccine (OPV). Considering the protective non-specific effects (NSE) of OPV on unrelated pathogens, the withdrawal may impact child health negatively. Within a cluster-randomized trial, we carried out 16S rRNA deep sequencing analysis of fecal and nasopharyngeal microbial content of Bissau-Guinean infants aged 4-8 months, before and after 2 months of OPV revaccination (revaccinated infants = 47) vs. no OPV revaccination (control infants = 47). The aim was to address changes in the gut and upper respiratory bacterial microbiotas due to revaccination. Alpha-diversity for both microbiotas increased similarly over time in OPV-revaccinated infants and controls, whereas greater changes over time in the bacterial composition of gut (p adjusted < 0.001) and upper respiratory microbiotas (p adjusted = 0.018) were observed in the former. Taxonomic analysis of gut bacterial microbiota revealed a decrease over time in the median proportion of Bifidobacterium longum for all infants (25-14.3%, p = 0.0006 in OPV-revaccinated infants and 25.3-11.6%, p = 0.01 in controls), compatible with the reported weaning. Also, it showed a restricted increase in the median proportion of Prevotella_9 genus in controls (1.4-7.1%, p = 0.02), whereas in OPV revaccinated infants an increase over time in Prevotellaceae family (7.2-17.4%, p = 0.005) together with a reduction in median proportion of potentially pathogenic/opportunistic genera such as Escherichia/Shigella (5.8-3.4%, p = 0.01) were observed. Taxonomic analysis of upper respiratory bacterial microbiota revealed an increase over time in median proportions of potentially pathogenic/opportunistic genera in controls, such as Streptococcus (2.9-11.8%, p = 0.001 and Hemophilus (11.3-20.5%, p = 0.03), not observed in OPV revaccinated infants. In conclusion, OPV revaccination was associated with a healthier microbiome composition 2 months after revaccination, based on a more abundant and diversified bacterial community of Prevotellaceae and fewer pathogenic/opportunistic organisms. Further information on species-level differentiation and functional analysis of microbiome content are warranted to elucidate the impact of OPV-associated changes in bacterial microbiota on child health.

Atlantic Forest Malaria: A Review of More than 20 Years of Epidemiological Investigation.

In the south and southeast regions of Brazil, cases of malaria occur outside the endemic Amazon region near the Atlantic Forest in some coastal states, where Plasmodium vivax is the recognized parasite. Characteristics of cases and vectors, especially Anopheles (Kerteszia) cruzii, raise the hypothesis of a zoonosis with simians as reservoirs. The present review aims to report on investigations of the disease over a 23-year period. Two main sources have provided epidemiological data: the behavior of Anopheles vectors and the genetic and immunological aspects of Plasmodium spp. obtained from humans, Alouatta simians, and Anopheles spp. mosquitoes. Anopheles (K.) cruzii is the most captured species in the forest canopy and is the recognized vector. The similarity between P. vivax and Plasmodium simium and that between Plasmodium malariae and Plasmodium brasilianum shared between simian and human hosts and the involvement of the same vector in the transmission to both hosts suggest interspecies transfer of the parasites. Finally, recent evidence points to the presence of Plasmodium falciparum in a silent cycle, detected only by molecular methods in asymptomatic individuals and An. (K.) cruzii. In the context of malaria elimination, it is paramount to assemble data about transmission in such non-endemic low-incidence areas.

Knockdown of the Plasmodium falciparum SURFIN4.1 antigen leads to an increase of its cognate transcript.

The genome of the malaria parasite Plasmodium falciparum contains the surf gene family which encodes large transmembrane proteins of unknown function. While some surf alleles appear to be expressed in sexual stages, others occur in asexual blood stage forms and may be associated to virulence-associated processes and undergo transcriptional switching. We accessed the transcription of surf genes along multiple invasions by real time PCR. Based on the observation of persistent expression of gene surf4.1, we created a parasite line which expresses a conditionally destabilized SURFIN4.1 protein. Upon destabilization of the protein, no interference of parasite growth or morphological changes were detected. However, we observed a strong increase in the transcript quantities of surf4.1 and sometimes of other surf genes in knocked-down parasites. While this effect was reversible when SURFIN4.1 was stabilized again after a few days of destabilization, longer destabilization periods resulted in a transcriptional switch away from surf4.1. When we tested if a longer transcript half-life was responsible for increased transcript detection in SURFIN4.1 knocked-down parasites, no alteration was found compared to control parasite lines. This suggests a specific feedback of the expressed SURFIN protein to its transcript pointing to a novel type of regulation, inedited in Plasmodium.

Respiratory microbiota and lower respiratory tract disease.

INTRODUCTION: The respiratory airways harbor a complex succession of ecological niches with distinct but related bacterial communities. Particular challenges of respiratory microbiome research have led to limited scientific output compared to other human microbiomes. Areas covered: In this review, we summarize the current state of knowledge of the bacterial respiratory microbiome, with a particular focus on associations between the respiratory microbiome and lower respiratory tract conditions. Expert commentary: There is growing evidence that the respiratory microbiome is associated with lower respiratory infectious diseases and related conditions. Most respiratory microbiome reports are metataxonomic cross-sectional or case-control studies with relatively small sample sizes. Large, prospective projects with metatranscriptomics or metabolomics approach are needed to unravel the effect of the respiratory microbiome on health-related conditions. Moreover, standardization in sampling, library preparation, sequencing techniques and data analysis should be encouraged.

Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon.

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms.

Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms. .