Search Results (1,158)

Cerebral malaria in young African children is associated with high mortality, and persisting neurological deficits often remain in survivors. Sequestered Plasmodium-infected red blood cells lead to cerebrovascular inflammation and subsequent neuroinflammation. Brain inflammation can play a role in the pathogenesis of neurologic sequelae. Therefore, we assessed a select set of proinflammatory analytes (IP10, IL23, MIP3α, GRO, MCP-1, and osteopontin in both the plasma and cerebrospinal fluid(CSF) of Zambian children with cerebral malaria and compared this with children with neurological symptoms that were negative for Plasmodium falciparum (non-cerebral malaria). Several similarities in plasma and CSF levels were found, as were some striking differences. We confirmed that IP10 levels were higher in the plasma of cerebral malaria patients, but this was not found in CSF. Levels of osteopontin were elevated in both the plasma and CSF of CM patients compared to the non-CM patients. These results show again a highly inflammatory environment in both groups but a different profile for CM when compared to non-cerebral malaria. Osteopontin may play an important role in neurological inflammation in CM and the resulting sequelae. Therefore, osteopontin could be a valid target for further biomarker research and potentially for therapeutic interventions in neuroinflammatory infections. Full article

Hemozoin (Hz) is a heme crystal produced during malaria infection that stimulates immune cells, leading to the production of cytokines and chemokines. The immunostimulatory action of Hz has previously been applied in the development of alternative adjuvants. Crystallization of hemin is a chemical approach for producing Hz. Here, we focused on an enzymatic production method for Hz using the heme detoxification protein (HDP), which catalyzes heme dimer formation from hemin in Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading to the production of interleukin (IL)-6 and IL-12p40. In mice, subcutaneous administration of esHz together with an antigen, ovalbumin (OVA), increased the OVA-specific immunoglobulin (Ig) G2c isotype level in the serum, whereas OVA-specific IgG1 was not induced. Our findings suggest that esHz is a useful Th-1 cell adjuvant. Full article

The invasion of Anopheles stephensi into Africa poses a potential threat to malaria control and elimination on the continent. However, it is not clear if the recent malaria resurgence in Ethiopia has linked to the expansion of An. stephensi. We obtained the clinical malaria case reports and malaria intervention data from the Ethiopian Ministry of Health (MoH) for the period 2001–2022. We analyzed clinical malaria hotspots and investigated the potential role of An. stephensi in the 2022 malaria outbreaks. Clinical malaria cases in Ethiopia decreased by 80%, from 5.2 million cases in 2004 to 1.0 million cases in 2018; however, cases increased steadily to 2.6 million confirmed cases in 2022. Plasmodium vivax cases and proportion have increased significantly in the past 5 years. Clinical malaria hotspots are concentrated along the western Ethiopian border areas and have grown significantly from 2017 to 2022. Major malaria outbreaks in 2022/2023 were detected in multiple sites across Ethiopia, and An. stephensi was the predominant vector in some of these sites, however, it was absence from many of the outbreak sites. The causes of recent upsurge in malaria in Ethiopia may be multi-factorial and it is a subject of further investigation. Full article

In the global fight against malaria, standard vector control methods such as indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are intended to protect inside residential structures and sleeping spaces. However, these methods can still leave individuals vulnerable to residual transmission from vectors that they may be exposed to outdoors. Nchelenge District in northern Zambia experiences persistently high malaria transmission even with ITNs and IRS in place. However, very few studies have examined outdoor vector activity. To assess the diversity and abundance of outdoor foraging female anopheline mosquitoes, CDC light traps were used as proxy measures for mosquito host-seeking, set in three outdoor trapping schemes randomly assigned on different nights: (1) locations where people congregate at night outside of the house within the peri-domestic space, (2) animal pens or shelters, and (3) high-human-traffic areas, such as paths to latrines, where traps were baited with BG-Lure^®. A total of 1087 total female anophelines were collected over a total of 74 trap nights. Anopheles funestus s.s. comprised the majority of the collection (86%), with An. gambiae s.s. (2%) and a highly diverse sampling of other anophelines (12%) making up the remainder. Plasmodium falciparum parasites were only detected in An. funestus (1%). No significant difference in species diversity or female anopheline abundance was detected between trapping schemes. Outdoor foraging anopheline mosquitoes, including a number of infectious An. funestus, may partially explain the difficulty of controlling malaria transmission in Nchelenge District, where vector control is only targeted indoors. BG-Lure^® shows some promise as an alternative to human-baited landing catch collections in this resource-poor setting. Full article

Culters are a popular and economically important carnivorous freshwater fish, widely distributed in rivers, lakes, and reservoirs in China. An investigation of Myxozoa was conducted to enhance the understanding of Myxozoan diversity in Culters in China, as only 15 Myxosporean species have been previously reported in 6 Culters species. A new species with typical Myxobolus characteristics was discovered exclusively in the gills of Chanodichthys dabryi, Bleeker, 1871, and no other species were found in other Culters fish or organs. The new species elicited whitish plasmodia in the serosa layer of the gill arch, with no distinct inflammatory reaction observed. This species is morphologically different from all reported Myxobolus spp. from Culters, differing in plasmodium and spore size, as well as the coils of polar filaments. Molecular analysis further supports that it does not match any sequences available in GenBank. Therefore, we identified it as a new species and named it Myxobolus dabryi n. sp. Full article

The Plasmodium falciparum mitochondrial electron transport chain (mETC) is responsible for essential metabolic pathways such as de novo pyrimidine synthesis and ATP synthesis. The mETC complex III (cytochrome bc₁ complex) is responsible for transferring electrons from ubiquinol to cytochrome c and generating a proton gradient across the inner mitochondrial membrane, which is necessary for the function of ATP synthase. Recent studies have revealed that the composition of Plasmodium falciparum complex III (PfCIII) is divergent from humans, highlighting its suitability as a target for specific inhibition. Indeed, PfCIII is the target of the clinically used anti-malarial atovaquone and of several inhibitors undergoing pre-clinical trials, yet its role in parasite biology has not been thoroughly studied. We provide evidence that the universally conserved subunit, PfRieske, and the new parasite subunit, PfC3AP2, are part of PfCIII, with the latter providing support for the prediction of its divergent composition. Using inducible depletion, we show that PfRieske, and therefore, PfCIII as a whole, is essential for asexual blood stage parasite survival, in line with previous observations. We further found that depletion of PfRieske results in gametocyte maturation defects. These phenotypes are linked to defects in mitochondrial functions upon PfRieske depletion, including increased sensitivity to mETC inhibitors in asexual stages and decreased cristae abundance alongside abnormal mitochondrial morphology in gametocytes. This is the first study that explores the direct role of the PfCIII in gametogenesis via genetic disruption, paving the way for a better understanding of the role of mETC in the complex life cycle of these important parasites and providing further support for the focus of antimalarial drug development on this pathway. Full article

Tafenoquine (TQ) is a new 8-aminoquinoline antimalarial drug developed by the US Army for Plasmodium vivax malaria treatment. Modeling and simulation are essential tools for drug development and improving rationality in pharmacotherapy, and different modeling approaches are used. This study aims to summarize and explore the pharmacokinetic (PK) models available for tafenoquine in the literature. An integrative methodology was used to collect and review published data. Fifteen articles were identified using three modeling approaches: non-compartmental analysis (NCA), population pharmacokinetic analysis (popPK), and pharmacokinetic/pharmacodynamic analysis (PK/PD). An NCA was mainly used to describe the PK profile of TQ and to compare its PK profile alone to those obtained in association with other drugs. PopPK was used to assess TQ population PK parameters, covariates’ impact, and dose selection. PK/PD helped understand the relationship between TQ concentrations, some adverse events common for 8-aminoquilones, and the efficacy assessment for Plasmodium falciparum. In summary, pharmacokinetic models were widely used during TQ development. However, there is still a need for different modeling approaches to support further therapeutic questions, such as treatment for special populations and potential drug–drug interactions. Full article

The United States of America (US) has the highest annual number of human babesiosis cases caused by Babesia microti (Bm). Babesia, like malaria-causing Plasmodium, are protozoan parasites that live within red blood cells (RBCs). Both infectious diseases can be associated with hemolysis and organ damage, which can be fatal. Since babesiosis was made a nationally notifiable condition by the Centers for Disease Control and Prevention (CDC) in January 2011, human cases have increased, and drug-resistant strains have been identified. Both the Bm ligand(s) and RBC receptor(s) needed for invasion are unknown, partly because of the difficulty of developing a continuous in vitro culture system. Invasion pathways are relevant for therapies (e.g., RBC exchange) and vaccines. We hypothesize that there is at least one RBC surface antigen that is essential for Bm invasion and that all Bm hosts express this. Because most RBC surface antigens that impact Plasmodium invasion are in human blood group (hBG) systems, which are generated by 51 genes, they were the focus of this study. More than 600 animals with at least one hBG system gene ortholog were identified using the National Center for Biotechnology Information (NCBI) command-line tools. Google Scholar searches were performed to determine which of these animals are susceptible to Bm infection. The literature review revealed 28 Bm non-human hosts (NHH). For 5/51 (9.8%) hBG system genes (e.g., RhD), no NHH had orthologs. This means that RhD is unlikely to be an essential receptor for invasion. For 24/51 (47.1%) hBG system genes, NHH had 4–27 orthologs. For the ABO gene, 15/28 NHH had an ortholog, meaning that this gene is also unlikely to generate an RBC antigen, which is essential for Bm invasion. Our prior research showed that persons with blood type A, B, AB, O, RhD+, and RhD- can all be infected with Bm, supporting our current study’s predictions. For 22/51 (43.1%) hBG system genes, orthologs were found in all 28 NHH. Nineteen (37.3%) of these genes encode RBC surface proteins, meaning they are good candidates for generating a receptor needed for Bm invasion. In vitro cultures of Bm, experimental Bm infection of transgenic mice (e.g., a CD44 KO strain), and analyses of Bm patients can reveal further clues as to which RBC antigens may be essential for invasion. Full article

The control and management of malaria are linked to the quality of diagnosis. We sought to estimate the performance of routine microscopy for malaria diagnosis and assess the prevalence of submicroscopic Plasmodium (P.) falciparum infection among febrile patients in two healthcare facilities in Mossendjo, the Republic of the Congo. A cross-sectional study was conducted between January and December 2022. A total of 650 and 234 patients with signs of uncomplicated malaria were enrolled at the Centre de Sante Intégré (CSIMSJ) and Hôpital de Base (HBMSJ), respectively. Two thick blood smears were performed for each patient, one analyzed by routine microscopists and the other by an expert. The msp-1 and msp-2 genes were genotyped to detect submicroscopic P. falciparum infection. At the CSIMSJ, the sensitivity was 49.5% and the specificity was 88.6%. The positive and negative predictive values were 77.7% and 68.7%, respectively. At the HBMSJ, the sensitivity was 32.9% and the specificity was 79.4%. The positive and negative predictive values were 44.8% and 69.5%, respectively. P. falciparum was the only species detected by routine microscopists, while experts identified some cases with P. malariae and P. ovale. The proportion of submicroscopic infections was 35.75%. Children under 5 years old had higher rates of parasitemia. However, submicroscopic infections were more pronounced in the adult group. The performance of routine malaria microscopists at Mossendjo was inaccurate at both sites. With the large proportion of submicroscopic infection, malaria management at Mossendjo requires the improvement of microscopists’ skills and the concomitant use of RDTs. Full article

Plasmodium vivax causes the largest malaria burden in Brazil, and chloroquine resistance poses a challenge to eliminating malaria by 2035. Illegal mining in the Roraima Yanomami Indigenous territory can lead to the introduction of resistant parasites. This study aimed to investigate mutations in the pvcrt-o and pvmdr-1 genes to determine their potential as predictors of P. vivax chloroquine-resistant phenotypes. Samples were collected in two health centers of Boa Vista. A questionnaire was completed, and blood was drawn from each patient. Then, DNA extraction, PCR, amplicon purification, and DNA sequencing were performed. After alignment with the Sal-1, the amplified fragment was analyzed. Patients infected with the mutant parasites were queried in the Surveillance Information System. Among the patients, 98% (157/164) of participants were from illegal mining areas. The pvcrt-o was sequenced in 151 samples, and the K10 insertion was identified in 13% of them. The pvmdr1 was sequenced in 80 samples, and the MYF haplotype (958M) was detected in 92% of them and the TYF was detected in 8%, while the MYL was absent. No cases of recrudescence, hospitalization, or death were found. Mutations in the pvcrt-o and pvmdr-1 genes have no potential to predict chloroquine resistance in P. vivax. Full article

Malaria is a serious health problem worldwide affecting mainly children and socially vulnerable people. The biological particularities of P. vivax, such as the ability to generate dormant liver stages, the rapid maturation of gametocytes, and the emergence of drug resistance, have contributed to difficulties in disease control. In this context, developing an effective vaccine has been considered a fundamental tool for the efficient control and/or elimination of vivax malaria. Although recombinant proteins have been the main strategy used in designing vaccine prototypes, synthetic immunogenic peptides have emerged as a viable alternative for this purpose. Considering, therefore, that in the Brazilian endemic population, little is known about the profile of the humoral immune response directed to synthetic peptides that represent different P. vivax proteins, the present work aimed to map the epitope-specific antibodies’ profiles to synthetic peptides representing the linear portions of the ookinete and sporozoite cell passage protein (CelTOS), thrombospondin-related adhesive protein (TRAP), and cysteine-rich protective antigen (CyRPA) proteins in the acute (AC) and convalescent phases (Conv30 and Conv180 after infection) of vivax malaria. The results showed that the studied subjects responded to all proteins for at least six months following infection. For IgM, a few individuals (3–21%) were positive during the acute phase of the disease; the highest frequencies were observed for IgG (28–57%). Regarding the subclasses, IgG2 and IgG3 stood out as the most prevalent for all peptides. During the follow-up, the stability of IgG was observed for all peptides. Only one significant positive correlation was observed between IgM and exposure time. We conclude that for all the peptides, the immunodominant epitopes are recognized in the exposed population, with similar frequency and magnitude. However, if the antibodies detected in this study are potential protectors, this needs to be investigated. Full article

Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host’s body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain oxidative stress induced by Plasmodium berghei in male mice. Two protocols were applied in this study: the therapeutic and prophylactic protocols. The results of the therapeutic protocol revealed a significant decrease in the level of parasitemia caused by P. berghei. Additionally, the histopathological changes in various brain regions were markedly improved after treatment with betalains. Regarding the prophylactic protocol, betalains were able to protect the brain tissues from oxidative stress, inflammation, and disrupted neurotransmitters expected to occur as a result of infection by P. berghei. This was demonstrated by modulating the activities of brain antioxidants (SOD and GSH), inflammatory cytokines (IL-6, IL-10, IL-12, TNF-α, and INF-γ), and neurotransmitters (serotonin, epinephrine, and norepinephrine). This study has proven that using betalains as a treatment or as a preventive has a vital and effective role in confronting the brain histopathological, oxidative stress, and inflammatory changes induced by P. berghei infection. Full article

Malaria is a significant health problem in Africa, primarily due to the Plasmodium falciparum species, but this is not the only etiological factor responsible for malaria on the continent. The goal of the present research was to describe asymptomatic malaria cases and to identify Plasmodium species responsible for malaria in the BaAka Pygmies, inhabitants of the Central African Republic (CAR). Screening was realised in the period of August–September 2021 among 308 people, including 74 children and 234 adults reporting to a healthcare facility in Monasao (southwest CAR), an area inhabited by a semi-nomadic tribe of BaAka Pygmies. The study consisted of two phases. Phase I, which was conducted in Africa, consisted of performing malaria rapid diagnostic tests (mRDTs), taking haemoglobin measurements and collecting blood samples onto Whatman FTA cards for molecular diagnostics. Phase II, which was conducted in Poland, involved molecular tests (RT-PCR) to confirm or rule out malaria infections and to identify Plasmodium species responsible for the infections. mRDTs detected Plasmodium infections in 50.3% of children and 17.1% of adults participating in the study, whereas RT-PCR assays yielded positive results for 59.5% children and 28.6% adults. Molecular tests detected multiple Plasmodium falciparum infections but also three infections with P. malariae, three with P. ovale and one with P. vivax. The obtained results have confirmed numerous asymptomatic Plasmodium infections among the BaAka Pygmies. The rates of asymptomatic malaria cases in adults were twice as high as those in children, which may be indicative of the gradual acquisition of protective immunity with age. The study findings have also demonstrated that although most cases of malaria in Africa are caused by P. falciparum, three other species are also present in the region. Full article

Malaria during pregnancy has been associated with significant risks to both the mother and the fetus, leading to complications such as anemia, low birth weight, and increased infant mortality. The trophoblast cells, a key component of the placenta, are crucial for nutrient and oxygen exchange between mother and fetus. The differentiation of cytotrophoblasts (CTBs) into syncytiotrophoblasts (STBs) is critical for proper pregnancy development. These cells form the bi-stratified epithelium surrounding the placental villi. While previous studies have described an inflammatory activation of STB cells exposed to Plasmodium falciparum-infected erythrocytes (P. falciparum-IE) or components such as hemozoin (HZ), little is known about the direct effect this parasite may have on the epithelial turnover and function of trophoblast cells. This study aims to contribute to understanding mechanisms leading to placental damage during placental malaria using a BeWo cell line as a differentiation model. It was found that P. falciparum-IE interferes with the fusion of BeWo cells, affecting the differentiation process of trophoblast. A reduction in syncytialization could be associated with the adverse effects of infection in fetal health, altering the remodeling of the trophoblast epithelial barrier and reducing their capacity to exchange substances. However, further studies are necessary to assess alterations in the functionality of this epithelium. Full article

Raptors (Accipitriformes, Falconiformes and Strigiformes) are important for ecological niches as bioindicators and an apex predator; however, their global populations have continuously decreased due to human activities, habitat loss and contagious diseases. Avian malaria that may cause the negative impact on raptors’ health may also contribute to the declining of raptor populations. This study reported malaria’s molecular prevalence and genetic diversity in wild-caught and rehabilitated raptors in the Kasetsart University Raptor Rehabilitation Unit. In total, 109 raptors from 18 provinces of Thailand were classified into two groups, which included 78 diurnal raptors (DIRs) in Accipitriformes and 31 nocturnal raptors (NORs) in Strigiformes. Each ethylenediaminetetraacetic (EDTA) blood sample (0.5–1 mL) was tested through haematological analyses and polymerase chain reaction (PCR)-based detection to assess parasites’ health impacts. Amplicons of PCR positive samples were analysed for a nucleotide sequencing and phylogenetic relationships. The overall prevalence of avian malaria was low at 3.67% (4/109) (95% CI: 1.44–9.06%), with a prevalence of 3.86% (3/78) (95% CI: 1.32–10.70%) in DIRs and 3.23% (1/31) (95% CI: 1.32–10.70%) in NORs. Most of the infected samples were from southern Thailand. This suggested that the raptors in humid habitats are more vulnerable to the malarial infection, which was likely associated with vector and parasite abundance. Clinical appearances and haematological examinations demonstrated that raptors could tolerate the infection and only became asymptomatic and subclinically infected. This study is the first report of the infection of avian malaria in Cinerous Vulture, Himalayan Vulture and Barred Eagle Owl in Thailand, providing baseline information in preparedness for the disease diagnostic and further study of avian malaria in some endangered raptor species. Full article