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This study was conceived to investigate the pathogenicity of relapsed (Diminazene aceturate-resistant), field (original) and mixed (relapsed and field) isolates of Trypanosoma brucei brucei in rats. Twenty eight healthy adult albino rats of both sexes weighing between 149-177 gm were used to compare the pathogenicity of relapsed, field and the mixed isolates of T. brucei brucei infections. The rats were separated into four groups (A-D); where, group A was kept as uninfected control, and group B was infected with 1x103 trypanosomes of the field isolate and 1x103 trypanosomes of the diminazene aceturate resistant isolate. The rats of groups C and D were infected with 1x106 trypanosomes of the diminazene aceturate-resistant isolate and 1x106 trypanosomes of the field isolate, respectively. The infected rats became parasitemic within 4 to 8 days post-infection. The mean pre-patent periods (PP) were 4.1±1.1, 6.0±2.0 and 9.1±1.1 days in groups B, C and D respectively, while the mean survival time (ST) in groups B, C and D were 21.4±10.1, 27.1±13.2 and 34.0 ±12.8 days, respectively. The PP and ST were shortest (P<0.05) in group B (mixed infections), and level of parasitemia was higher (P<0.05) in group B (mixed infections) as compared to groups C and D. The level of anemia was comparable (P>0.05) in groups C and D and more severe (P<0.05) in group B. Mixed infections exhibit shortest PP, ST, higher level of parasitemia and more severe anemia, and appear to be more pathogenic.

Background Trypanosoma cruzi , the etiologic agent of Chagas disease, is currently divided into six discrete typing units (DTUs), named TcI-TcVI. TcII is among the major DTUs enrolled in human infections in South America southern cone, where it is associated with severe cardiac and digestive symptoms. Despite the importance of TcII in Chagas disease epidemiology and pathology, so far, no genome-wide comparisons of the mitochondrial and nuclear genomes of TcII field isolates have been performed to track the variability and evolution of this DTU in endemic regions. Results In the present work, we have sequenced and compared the whole nuclear and mitochondrial genomes of seven TcII strains isolated from chagasic patients from the central and northeastern regions of Minas Gerais, Brazil, revealing an extensive genetic variability within this DTU. A comparison of the phylogeny based on the nuclear or mitochondrial genomes revealed that the majority of branches were shared by both sequences. The subtle divergences in the branches are probably consequence of mitochondrial introgression events between TcII strains. Two T. cruzi strains isolated from patients living in the central region of Minas Gerais, S15 and S162a, were clustered in the nuclear and mitochondrial phylogeny analysis. These two strains were isolated from the other five by the Espinhaço Mountains, a geographic barrier that could have restricted the traffic of insect vectors during T. cruzi evolution in the Minas Gerais state. Finally, the presence of aneuploidies was evaluated, revealing that all seven TcII strains have a different pattern of chromosomal duplication/loss. Conclusions Analysis of genomic variability and aneuploidies suggests that there is significant genomic variability within Minas Gerais TcII strains, which could be exploited by the parasite to allow rapid selection of favorable phenotypes. Also, the aneuploidy patterns vary among T. cruzi strains and does not correlate with the nuclear phylogeny, suggesting that chromosomal duplication/loss are recent and frequent events in the parasite evolution.

Malaria elimination urgently needs novel antimalarial therapies that transcend resistance, toxicity, and high costs. Our multicentric international collaborative team focuses on developing multistage antimalarials that exhibit novel mechanisms of action. Here, we describe the design, synthesis, and evaluation of a novel multistage antimalarial compound, ‘Calxinin’. A compound that consists of hydroxyethylamine (HEA) and trifluoromethyl-benzyl-piperazine. Calxinin exhibits potent inhibitory activity in the nanomolar range against the asexual blood stages of drug-sensitive (3D7), multidrug-resistant (Dd2), artemisinin-resistant (IPC4912), and fresh Kenyan field isolated Plasmodium falciparum strains. Calxinin treatment resulted in diminished maturation of parasite sexual precursor cells (gametocytes) accompanied by distorted parasite morphology. Further, in vitro liver-stage testing with a mouse model showed reduced parasite load at an IC50 of 79 nM. A single dose (10 mg/kg) of Calxinin resulted in a 30% reduction in parasitemia in mice infected with a chloroquine-resistant strain of the rodent parasite P. berghei. The ex vivo ookinete inhibitory concentration within mosquito gut IC50 was 150 nM. Cellular in vitro toxicity assays in the primary and immortalized human cell lines did not show cytotoxicity. A computational protein target identification pipeline identified a putative P. falciparum membrane protein (Pf3D7_1313500) involved in parasite calcium (Ca2+) homeostasis as a potential Calxinin target. This highly conserved protein is related to the family of transient receptor potential cation channels (TRP-ML). Target validation experiments showed that exposure of parasitized RBCs (pRBCs) to Calxinin induces a rapid release of intracellular Ca2+ from pRBCs; leaving de-calcinated parasites trapped in RBCs. Overall, we demonstrated that Calxinin is a promising antimalarial lead compound with a novel mechanism of action and with potential therapeutic, prophylactic, and transmission-blocking properties against parasites resistant to current antimalarials.

Porcine parvovirus 5 (PPV5) is a novel virus frequently detected in pigs worldwide. However, its identification and prevalence in domestic pigs in Russia have not been described. In this study, retrospectively, 984 serum samples collected between 2020 and 2023 were tested by qPCR. All samples were obtained from 20 pig farms located in 10 regions of Russia. PPV5 circulation was confirmed in 11 pig farms with the overall detection rate at 8.9%. The highest detection rate was estimated in the farms of the Belgorod Region (17.1%), followed by the Sverdlovsk Region (15.9%), the Republic of Buryatia (14.7%), and the Moscow Region (14.0%). It has been confirmed that PPV5 has been circulating in the swine population since at least 2021. The phylogenetic analysis revealed a high nucleotide identity of Russian isolates with strains from the USA, Colombia, and China. The Moscow-4060 strain was isolated in primary porcine testicular cells (PPTCs), and its continuous replication was confirmed by qPCR. During microscopy, cytoplasmic vacuolization, pyknosis, and other alterations were observed. The results demonstrate the evidence of PPV5 circulation in domestic pigs in Russia and the first isolation of the virus ever described. These findings serve as a first step for studying PPV5 in vivo.

Malaria continues to be a major health issue globally with almost 85% of the global burden and deaths borne by sub-Saharan Africa and India. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the ( ) parasite, compounding evidence of artemisinin and amodiaquine resistance establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies. The study was cross-sectional and was conducted during the peak malaria transmission seasons of 2015, 2016, and 2017 in two ecological zones of Ghana. Study participants included children aged 6 months to 14 years. Using ex vivo 4,6-diamidino-2-phenylindole (DAPI) drug sensitivity assay, 330 isolates were used to investigate susceptibility to five antimalarial drugs: chloroquine (CQ), amodiaquine (AMD) dihydroartemisinin (DHA), artesunate (ART) and mefloquine (MFQ). The pooled geometric mean IC S (GMIC ) of the five drugs against the parasites from Cape Coast and Begoro were 15.5, 42.4, 18.9, 4.6 and 27.3nM for CQ, AMD, DHA, ART, and MFQ, respectively. The GMIC values for CQ (p<0.001), ART (p<0.011) and DHA (p<0.018) were significantly higher for Cape Coast isolates as compared to Begoro isolates. However, GMIC estimates for MFQ (p<0.022) were significantly higher for Begoro isolates. Positive correlations were found between each pair of drugs with the weakest found between MFQ and DHA ( = 0.34;p<0.001), and the strongest between ART and DHA ( =0.66; p<0.001). The parasites showed reduced sensitivities to three (AMD, DHA and MFQ) out of the five drugs assessed. The study also demonstrated the continual return of chloroquine-sensitive parasites after 13 years of its withdrawal as the first-line drug for the treatment of uncomplicated malaria in Ghana. The ex vivo DAPI assay is a reliable method for assessing antimalarial drug sensitivities of field isolates under field settings.

Background Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates. Results In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype. Conclusions The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug resistance phenotypes in vivo .

African swine fever virus (ASFV) is endemic to African wild pigs (Phacochoerus and Potamochoerus), in which viral infection is asymptomatic, and Ornithodoros soft ticks. However, ASFV causes a lethal disease in Eurasian domestic pigs (Sus scrofa). While Sub-Saharan Africa is believed to be the original home of ASFV, publicly available whole-genome ASFV sequences show a strong bias towards p72 Genotypes I and II, which are responsible for domestic pig pandemics outside Africa. To reduce this bias, we hereby describe nine novel East African complete genomes in p72 Genotype IX and present the phylogenetic analysis of all 16 available Genotype IX genomes compared with other ASFV p72 clades. We also document genome-level differences between one specific novel Genotype IX genome sequence (KE/2013/Busia.3) and a wild boar cell-passaged derivative. The Genotype IX genomes clustered with the five available Genotype X genomes. By contrast, Genotype IX and X genomes were strongly phylogenetically differentiated from all other ASFV genomes. The p72 gene region, on which the p72-based virus detection primers are derived, contains consistent SNPs in Genotype IX, potentially resulting in reduced sensitivity of detection. In addition to the abovementioned cell-adapted variant, eight novel ASFV Genotype IX genomes were determined: five from viruses passaged once in primary porcine peripheral blood monocytes and three generated from DNA isolated directly from field-sampled kidney tissues. Based on this methodological simplification, genome sequencing of ASFV field isolates should become increasingly routine and result in a rapid expansion of knowledge pertaining to the diversity of African ASFV at the whole-genome level.

Chicken coccidiosis is an intestinal protozoan disease caused by Eimeria , which is distributed worldwide and causes significant economic losses in the poultry industry. Owing to prolonged anticoccidial use, drug resistance has become an important obstacle to the control of coccidiosis. This study aimed to evaluate the pathogenicity of three mixed-species Eimeria isolates collected from chicken farms in Sichuan Province, China. The drug resistance of the isolates was also evaluated, including synthetic drugs, ionophores, and a natural herb. A total of 132 newborn chicks were grouped, including an infected-treated group, a positive control for each isolate, and a negative control. Survival rate, weight gain, oocyst excretion, and lesion scores were recorded. The pathogenicity and drug resistance of the three isolates were determined by four indices, including the anticoccidial index (ACI), the optimal percentage of anticoccidial activity (POAA), the relative oocyst production (ROP), and the reduction of lesion score (RLS). The results showed that only one Eimeria spp. isolated from Xichang was sensitive to sulfaclozine, whereas the rest of the isolates exhibited resistance to all tested drugs, with most isolates demonstrating severe or complete resistance. These findings are crucial for the selection of a regional drug administration program to control coccidiosis in chickens.

The control of classical swine fever (CSF) in endemic areas has been attempted with modified live vaccines. However, in some regions, the implementation of imperfect vaccination programs has led to a reduction in the genetic diversity of the circulating CSF virus (CSFV) strains and a change in their virulence. Porvac® subunit vaccine has been shown to provide a rapid onset of protection against the “Margarita” strain. The aim of this study was to evaluate whether the immune response induced by Porvac® is also effective against autochthonous CSFV isolates of low, medium or high virulence. All pigs vaccinated with Porvac® were protected against the disease after challenge. PR-11/10–3 isolate caused a very mild disease in controls, whilst Holguin_2009 isolate produced mild to moderate signs of CSF and one of the pigs died. Finally, controls inoculated with PR-2016 isolate developed moderate to severe signs of CSF and two of them died. Viral replication was detected in controls, but not in pigs immunized with Porvac®. Finally, anti-Erns antibodies were induced in five out of six control pigs but not in any of the vaccinated pigs. These results support the use of Porvac® for the control and elimination of CSF in Cuba and other endemic regions.

Type II reference isolates of Toxoplasma gondii are widely used in animal toxoplasmosis models, but studies with Type III isolates remain scarce. In addition, these methods often rely on laboratory-adapted parasite stages that may not reflect natural infection. This study presents a new murine model based on an oral infection with oocysts from a recently obtained Type III isolate, TgShSp24, which exhibited remarkable morbidity and a distinct tissue distribution during chronic infection, differing from the recently obtained Type II isolate TgShSp1. This novel model aims to better mimic natural infection and provides a valuable tool for testing drugs and vaccines.