- MeSH
- antimalarika terapeutické užití MeSH
- cestovní nemoci MeSH
- dospělí MeSH
- fatální výsledek MeSH
- léková rezistence MeSH
- lidé MeSH
- malárie * diagnóza farmakoterapie mortalita MeSH
- Plasmodium falciparum patogenita MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Geografické názvy
- Tanzanie MeSH
Trained immunity is defined as an enhanced state of the innate system which leads to an improved immune response against related or non-related pathogens. Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis strain, is currently one of the main inductors of trained immunity. The objective of the present study was to evaluate the protective effects of heat-inactivated M. bovis (HIMB) against Plasmodium berghei and Borrelia burgdorferi and characterize the immunological mechanisms involved. BALB/c and C3H/HeN mice were randomly assigned in similar number to either immunized group receiving two oral doses of HIMB with a 4-week interval, or control group treated with PBS. All the BALB/c mice were intraperitoneally infected with P. berghei while the C3H/HeN mice were subcutaneously infected with B. burgdorferi. Pathogen burden was significantly reduced in both immunized groups when compared to controls. The number of macrophages significantly decreased in the liver or in the spleen of the mice that had been immunized prior to the challenge with P. berghei or B. burgdorferi, respectively. Furthermore, the immunized groups showed an apparent upregulation of IFN-γ, TNF-α and IL-1α in the liver (P. berghei challenge) or a significant increase in IL-1α producing cells in the spleen (B. burgdorferi challenge). Our findings suggest that oral immunization with heat-inactivated mycobacteria limits pathogen burden through stimulation of the innate immune response in two vector-borne diseases in mice.
- MeSH
- adjuvancia imunologická * aplikace a dávkování MeSH
- BCG vakcína * imunologie aplikace a dávkování MeSH
- Borrelia burgdorferi imunologie MeSH
- cytokiny MeSH
- inaktivované vakcíny imunologie aplikace a dávkování MeSH
- interferon gama imunologie MeSH
- interleukin-1alfa imunologie MeSH
- játra imunologie MeSH
- lymeská nemoc * prevence a kontrola imunologie MeSH
- makrofágy imunologie MeSH
- malárie * prevence a kontrola imunologie MeSH
- Mycobacterium bovis * imunologie MeSH
- myši inbrední BALB C MeSH
- myši inbrední C3H MeSH
- myši MeSH
- Plasmodium berghei imunologie MeSH
- protilátky bakteriální krev MeSH
- slezina imunologie mikrobiologie MeSH
- TNF-alfa imunologie MeSH
- vysoká teplota MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The human pathogens Plasmodium and Schistosoma are each responsible for over 200 million infections annually, especially in low- and middle-income countries. There is a pressing need for new drug targets for these diseases, driven by emergence of drug-resistance in Plasmodium and an overall dearth of drug targets against Schistosoma. Here, we explored the opportunity for pathogen-hopping by evaluating a series of quinoxaline-based anti-schistosomal compounds for their activity against P. falciparum. We identified compounds with low nanomolar potency against 3D7 and multidrug-resistant strains. In vitro resistance selections using wildtype and mutator P. falciparum lines revealed a low propensity for resistance. Only one of the series, compound 22, yielded resistance mutations, including point mutations in a non-essential putative hydrolase pfqrp1, as well as copy number amplification of a phospholipid-translocating ATPase, pfatp2, a potential target. Notably, independently generated CRISPR-edited mutants in pfqrp1 also showed resistance to compound 22 and a related analogue. Moreover, previous lines with pfatp2 copy number variations were similarly less susceptible to challenge with the new compounds. Finally, we examined whether the predicted hydrolase activity of PfQRP1 underlies its mechanism of resistance, showing that both mutation of the putative catalytic triad and a more severe loss of function mutation elicited resistance. Collectively, we describe a compound series with potent activity against two important pathogens and their potential target in P. falciparum.
- MeSH
- antimalarika * farmakologie MeSH
- chinoxaliny * farmakologie MeSH
- léková rezistence účinky léků MeSH
- lidé MeSH
- Plasmodium falciparum * účinky léků MeSH
- protozoální proteiny metabolismus genetika MeSH
- Schistosoma účinky léků MeSH
- schistosomóza farmakoterapie MeSH
- tropická malárie farmakoterapie parazitologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cryptosporidium mortiferum, a parasite transmitted by squirrels, is beginning to spread in Europe. C. mortiferum was detected in a symptomatic human. A 44-year-old man from the Czech Republic suffered from gastroenteritis characterized by abdominal pain, nausea, and loose stools. Molecular analyses confirmed the XIVaA20G2T1 subtype in the patient's stool. At the same time, the same subtype of C. mortiferum was detected in three red squirrels and two ground squirrels in the area where the patient lived. The intensity of the infection was significantly higher in the red squirrels that died, while the ground squirrels showed no symptoms. The results of the study indicate that red squirrels and ground squirrels are the reservoirs for the infection.
- MeSH
- Cryptosporidium * izolace a purifikace genetika klasifikace MeSH
- dospělí MeSH
- feces * parazitologie MeSH
- fylogeneze MeSH
- gastroenteritida parazitologie veterinární MeSH
- kryptosporidióza * parazitologie epidemiologie MeSH
- lidé MeSH
- Sciuridae * parazitologie MeSH
- zdroje nemoci parazitologie MeSH
- zoonózy * parazitologie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Česká republika MeSH
PURPOSE: A new high-resolution next-generation sequencing (NGS)-based method was established to type closely related European type II Toxoplasma gondii strains. METHODS: T. gondii field isolates were collected from different parts of Europe and assessed by whole genome sequencing (WGS). In comparison to ME49 (a type II reference strain), highly polymorphic regions (HPRs) were identified, showing a considerable number of single nucleotide polymorphisms (SNPs). After confirmation by Sanger sequencing, 18 HPRs were used to design a primer panel for multiplex PCR to establish a multilocus Ion AmpliSeq typing method. Toxoplasma gondii isolates and T. gondii present in clinical samples were typed with the new method. The sensitivity of the method was tested with serially diluted reference DNA samples. RESULTS: Among type II specimens, the method could differentiate the same number of haplotypes as the reference standard, microsatellite (MS) typing. Passages of the same isolates and specimens originating from abortion outbreaks were identified as identical. In addition, seven different genotypes, two atypical and two recombinant specimens were clearly distinguished from each other by the method. Furthermore, almost all SNPs detected by the Ion AmpliSeq method corresponded to those expected based on WGS. By testing serially diluted DNA samples, the method exhibited a similar analytical sensitivity as MS typing. CONCLUSION: The new method can distinguish different T. gondii genotypes and detect intra-genotype variability among European type II T. gondii strains. Furthermore, with WGS data additional target regions can be added to the method to potentially increase typing resolution.
- MeSH
- genetická variace MeSH
- genotyp MeSH
- lidé MeSH
- multiplexová polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- protozoální DNA genetika MeSH
- těhotenství MeSH
- Toxoplasma * genetika MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Equine neosporosis is an intracellular protozoan disease with a global distribution, affecting a diverse range of warm-blooded animals. Neospora caninum Dubey, Carpenter, Speer, Topper et Uggla, 1988 is associated with foetal loss, neurological disease and abortion in equids. No information was available regarding equine N. caninum infection among equids in Iraq. Thus, the aim of this study was to determine the prevalence rate of N. caninum in equines by using a competitive enzyme-linked immunosorbent assay (c-ELISA). A total of 329 blood samples randomly selected from equines, comprising 268 horses and 61 donkeys were examined. The seroprevalence rate of N. caninum was determined as 46% (28/61) for donkeys and 24% (64/268) for horses. The prevalence of N. caninum indicated a significantly higher risk of infection in donkeys compared to horses (P < 0.001). However, the odds of N. caninum infection in draught equids were 8.2 times greater than other equids with a significant difference (P < 0.001). The current study revealed no significant differences in the prevalence of N. caninum across various genders, breeds, clinical statuses, disease histories and among equids that had contact with dogs. While outdoor feeding and mixed (grazing), showed a significant difference (P = 0.003) and (P = 0.75), respectively, in the presence of antibodies against N. caninum compared to indoor feeding (stable). Moreover, the odds of infection in equids with a history of late abortion were 4.8 times higher than those without such a history of abortion (2.20-10.56) with statistical significance (P < 0.001).
- MeSH
- ELISA * veterinární MeSH
- Equidae * parazitologie MeSH
- kokcidióza * veterinární epidemiologie parazitologie MeSH
- koně MeSH
- nemoci koní * epidemiologie parazitologie MeSH
- Neospora * izolace a purifikace MeSH
- prevalence MeSH
- protilátky protozoální krev MeSH
- séroepidemiologické studie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Irák MeSH
Cíl: Zjistit výskyt potenciálně patogenních druhů babesií pro člověka v klíšťatech a v krvi psů a jelenů ve vybraných regionech České republiky. Prevalenci Babesia spp. v klíšťatech porovnat s výskytem jiných patogenů přenášených klíšťaty jako Borrelia spp., Anaplasma spp., Rickettsia spp. Materiál a metody: Vzorky klíšťat byly jednotlivě homogenizovány, ze vzorků klíšťat a krve živočichů provedena izolace DNA. Detekce Babesia spp. byla stanovena metodou PCR 18S rRNA genu a sekvenační analýzou PCR produktů určeny jednotlivé druhy babesií. Výsledky: V letech 2014–2016 byla analyzována klíšťata a krev psů a jelenů na různých místech České republiky. Ze souboru 675 klíšťat Ixodes ricinus dosahovala pozitivita na přítomnost Babesia spp. hodnot od 0,0 do 3,3 %. Sekvenační analýzou byly v klíšťatech identifikovány druhy Babesia venatorum, Babesia microti (patogenní druhy pro člověka) a druh Babesia capreoli. Prevalence Babesia spp. v klíšťatech byla v porovnání s výskytem jiných patogenů jako Borrelia burgdorferi s. l. (29,3 %), Anaplasma phagocytophilum (4,9 %) nižší a srovnatelná s Rickettsia spp. (1,6 %). U třetiny pozitivních klíšťat na babesie byla zjištěna koinfekce s Borrelia burgdorferi s. l. (B. venatorum – Borrelia garinii, Borrelia afzelii a B. microti – B. afzelii). Ze 109 vzorků krve psů bylo 3,7 % pozitivních na Babesia spp. s výskytem druhů Babesia gibsoni a Babesia vulpes. Z 50 vzorků krve jelenů z přírodního ekosystému dosahovala pozitivita 4,0 %. Identifikován byl druh Babesia divergens, nejvíce patogenní druh Babesia spp. pro člověka. Z 80 vzorků krve jelenů chovaných na farmách bylo pozitivních 5,0 % s výskytem druhu Babesia odocoilei. Nukleotidové sekvence babesií způsobujících humánní babesiózu byly zaslány do genové banky a přijaty pod čísly ON892053 (B. venatorum), ON892061 (B. microti), ON892067 (B. divergens). Závěr: Metodou PCR 18S rRNA genu a sekvenací amplikonů byly na území České republiky detekovány tři druhy babesií patogenních pro člověka: B. divergens, B. venatorum, B. microti. Výskyt těchto druhů babesií znamená potenciální riziko onemocnění babesiózou, zejména pro asplenické a imunokompromitované pacienty. Zjištěné koinfekce s Borrelia burgdorferi s. l. mohou být příčinou komplikovaného průběhu onemocnění.
Aim: To determine the occurrence of species of Babesia potentially pathogenic for humans in ticks and in the blood of dogs and deer in selected regions of the Czech Republic. To compare the prevalence of Babesia spp. in ticks with that of other tick-borne pathogens, such as Borrelia spp., Anaplasma spp., and Rickettsia spp. Material and Methods: Tick samples were individually homogenized. DNA was isolated from tick samples and animal blood. The detection of Babesia spp. was based on PCR of the 18S rRNA gene, and the identification to the species level was done by sequencing analysis of the PCR products. Results: In 2014–2016, ticks and blood of dogs and deer collected in various areas of the Czech Republic were analyzed. In a set of 675 Ixodes ricinus ticks, the positivity rate for Babesia spp. varied from 0.0 to 3.3 %. The species Babesia venatorum, Babesia microti (both pathogenic for humans), and Babesia capreoli were identified in ticks by sequencing analysis. The prevalence of Babesia spp. in ticks compared to that of other pathogens such as Borrelia burgdorferi s. l. (29.3 %) or Anaplasma phagocytophilum (4.9 %) was lower and comparable to that of Rickettsia spp. (1.6 %). Co-infection with Borrelia burgdorferi s.l (B. venatorum – Borrelia garinii, Borrelia afzelii, and B. microti – B. afzelii) was found in a third of Babesia spp. positive ticks. Out of 109 dog blood samples, 3.7 % were positive for Babesia spp., specifically Babesia gibsoni and Babesia vulpes. Of 50 blood samples of wild deer from the natural ecosystem, the positivity rate reached 4.0 %. The species Babesia divergens, a major human pathogen, was identified. Out of 80 blood samples from farmed deer, 5.0 % were positive for the species Babesia odocoilei. Nucleotide sequences of the agents causing human babesiosis were deposited in the gene bank under accession numbers ON892053 (B. venatorum), ON892061 (B. microti), and ON892067 (B. divergens). Conclusions: Using PCR of the 18S rRNA gene and amplicon sequencing, three species of Babesia causing human babesiosis were detected in the Czech Republic: B. divergens, B. venatorum, and B. microti. Babesia spp. pathogenic for humans pose a potential risk especially in asplenic and immunocompromised patients. The detected co-infections with Borrelia spp. can be the cause of a complicated course of the disease.
- MeSH
- Babesia mikrobiologie MeSH
- babezióza * epidemiologie krev přenos MeSH
- Borrelia burgdorferi MeSH
- diagnostické techniky molekulární metody MeSH
- klíšťata * mikrobiologie MeSH
- koinfekce diagnóza přenos MeSH
- krev mikrobiologie MeSH
- lidé MeSH
- nemoci přenášené klíšťaty epidemiologie přenos prevence a kontrola MeSH
- polymerázová řetězová reakce metody MeSH
- psi * mikrobiologie MeSH
- vysoká zvěř * krev mikrobiologie MeSH
- Check Tag
- lidé MeSH
- psi * mikrobiologie MeSH
- Geografické názvy
- Česká republika MeSH
Malaria remains a major health hazard for humans, despite the availability of efficacious antimalarial drugs and other interventions. Given that the disease is often deadly for children under 5 years and pregnant women living in malaria-endemic areas, an efficacious vaccine to prevent transmission and clinical disease would be ideal. Plasmodium, the causative agent of malaria, uses proteases and protease inhibitors to control and process to invade host, modulate host immunity, and for pathogenesis. Plasmodium parasites rely on these proteases for their development and survival, including feeding their metabolic needs and invasion of both mosquito and human tissues, and have thus been explored as potential targets for prophylaxis. In this chapter, we have discussed the potential of proteases like ROM4, SUB2, SERA4, SERA5, and others as vaccine candidates. We have also discussed the role of some protease inhibitors of plasmodium and mosquito origin. Inhibition of plasmodium proteases can interrupt the parasite development at many different stages therefore understanding their function is key to developing new drugs and malaria vaccines.
- MeSH
- inhibitory proteas farmakologie terapeutické užití MeSH
- lidé MeSH
- malárie farmakoterapie imunologie parazitologie prevence a kontrola MeSH
- Plasmodium * účinky léků enzymologie imunologie fyziologie MeSH
- proteasy * imunologie MeSH
- protozoální proteiny * antagonisté a inhibitory imunologie MeSH
- vakcína proti malárii * imunologie MeSH
- vývoj vakcíny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In this review, I take the first-person perspective of a neuroscientist interested in Toxoplasma gondii (Nicolle et Manceaux, 1908). I reflect on the value of behavioural manipulation as a perturbation tool to understand the organisation of behaviour within the brain. Toxoplasma gondii infection reduces the aversion of rats to the olfactory cues of cat presence. This change in behaviour is one of the often-discussed exemplars of host-parasite coevolution, culminating in the manipulation of the host behaviour for the benefit of the parasite. Such coevolution also means that we can use host-parasite systems as tools to derive fundamental insights about the host brain itself.
- MeSH
- chování zvířat * fyziologie MeSH
- interakce hostitele a parazita * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- Toxoplasma * fyziologie MeSH
- toxoplazmóza zvířat parazitologie MeSH
- toxoplazmóza parazitologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Toxoplasmosis is caused by Toxoplasma gondii (Nicolle et Manceaux, 1908), a coccidian protist (Apicomplexa). It has a strong predilection for infecting the central nervous system. Researchers have therefore investigated its association with several neurological and psychiatric disorders, including Alzheimer's disease, attention-deficit hyperactivity disorder, autism, bipolar disorder, cerebral palsy, depression, Guillain-Barre syndrome, multiple sclerosis, obsessive compulsive disorder, Parkinson's disease, personality disorders, and schizophrenia. Among these disorders the strongest evidence for a role of T. gondii exists for psychosis in general and schizophrenia in particular. This paper reviews the origins of this association, briefly summarises the current evidence in support, and discusses future research strategies.
- MeSH
- lidé MeSH
- schizofrenie * MeSH
- Toxoplasma fyziologie MeSH
- toxoplazmóza * komplikace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH