Parasite Elimination Research Articles

Uncovering the Significance of JNK/AKT Axis in the Autophagic Regulation of Leishmania major Infection.

The role of autophagy in host induced by infection of parasites of the Leishmania genus remains inadequately understood. Leishmania parasites modulate host macrophages to promote its survival by inducing autophagy response in the host cell. In this study, we conducted an investigation of L. major infection, focusing on host autophagy processes where we reconstructed two mathematical models elucidating autophagy induction and inhibition processes and its impact on parasite survival. Our models presented systems modulatory dynamics of the parasite-mediated host autophagy. Our work highlighted the pivotal role of signaling molecules associated with the immune response which included signaling induced by Toll-like receptor (TLR), specifically through regulation of JNK and AKT. Both molecules emerged as key regulators of host autophagy process, highlighting that JNK/AKT signaling axis may be a potential avenue for innovative therapeutic approaches in targeting leishmaniasis. Also, ATG16L complex was identified as a critical determinant in shaping the course of leishmanial infection through formation of autophagosomes. Through invitro analyses in differentiated human monocyte cell line, we observed an increase in nitric oxide synthase (iNOS) concentration upon autophagy inhibition, while autophagy induction resulted in decreased iNOS concentration. This suggested that autophagy induction favors parasite survival in the host, potentially by providing a nutrient source that may be advantageous for the parasite. Inhibition of host autophagy promoted parasite elimination. Hence, our work proposed an avenue for strategically blocking host autophagy which enumerates a targeted approach for combating leishmaniasis.

Effects of Free and Nanoencapsulated Benznidazole in Acute Trypanosoma cruzi Infection: Role of Cholinergic Pathway and Redox Status

Background/Objectives: The Trypanosoma cruzi infection promotes an intense inflammatory process that affects several tissues. The cholinergic system may exert a regulatory immune response and control the inflammatory process. This study aimed to evaluate the comparative effect of free and nanoencapsulated benznidazole in acute T. cruzi infection to assess hematological, biochemical, and oxidative status triggered by the cholinergic system. Methods: For this, fifty female Swiss mice were distributed in eight groups, i.e., uninfected and infected animals under four treatment protocols: untreated (control—CT); vehicle treatment (Eudragit L 100—EL-100); benznidazole treatment (BNZ); and nanoencapsulated benznidazole treatment (NBNZ). After eight treatment days, the animals were euthanized for sample collection. Results: The peak of parasitemia was at day 7 p.i., and the BNZ and NBNZ controlled and reduced the parasite rate but showed no efficacy in terms of total elimination of parasites analyzed by RT-PCR in both infected groups. The infection promotes significant anemia, leukopenia, and thrombocytopenia, which the BNZ improves. There was an increase in AChE activity during infection, leading to a pro-inflammatory response and an increase in M1 and M2 mACh receptors in the BNZ group, showing that the treatment interacted with the cholinergic pathway. In addition, a pro-oxidative response was characterized in the infection and mainly in the infected BNZ and NBNZ groups. The histopathological analysis showed significative splenomegaly and inflammatory infiltrate in the heart, liver, and spleen. Conclusions: The administration of the BNZ or NBNZ reverses hematological, hepatic, and renal alterations through cholinergic signaling and stimulates a pro-inflammatory response during acute T. cruzi infection.

Enhancing agricultural sustainability through optimization of the slaughterhouse sludge compost for elimination of parasites and coliforms

For a sustainable ecology, slaughterhouse sludge must be managed effectively in preview of the parasitic or coliforms’ spill over to the community. In order to determine the effectiveness of a customized biological decomposer solution in lowering the parasitic eggs and coliform bacteria, three composting units (Unit 1, Unit 2, and Unit 3) were treated with its different amounts. Over a period of 60 days, pH, temperature, humidity, number of the parasitic eggs per gram (EPG) of faecal material, viability of eggs, and coliform counts were evaluated. By the fifth day of the composting process, pH had significantly (P < 0.05) increased across all the treatments and then decreased gradually. Also on the 5th day, all three units entered the thermophilic range (> 45 °C), which persisted for 20 days for Unit 3 and 15 days for Units 1 and 2. Humidity levels initially increased significantly (P < 0.05) in all three units (Unit 3 = 71%, Unit 2 = 64%, and Unit 1 = 55%) but then gradually decreased. On day 5, no decrease in EPG in Unit 1 was detected; however, a non-significant (P > 0.05) 12.5% decline in EPG in Unit 2 and Unit 3 was recorded. After that, a significant (P < 0.05) reduction in EPG was observed in all the three treatments until day 25. By day 5, decreased egg viability was significantly (P < 0.05) recorded in Unit 3 (21.43%); in Unit 1 and Unit 2, the decrease was 6.25% and 14.29%, respectively. Additionally, all units showed a significant (P < 0.05) decrease in total coliforms, meeting minimum allowable limit in Unit 2 and 3 on day 10 and on day 15 in Unit 1. The most substantial reduction in faecal coliforms was observed in Unit 3 (from 2.6 log₁₀ to 1.3 log₁₀), followed by Unit 2 (from 2.6 log₁₀ to 1.5 log₁₀), and then Unit 1 (from 2.6 log₁₀ to 1.6 log₁₀). The results of this study support recommendation of advanced composting techniques to eradicate or reduce the abundance of pathogens (parasites and coliforms). Hence, we endorse the value of careful composting procedures in environment-friendly abattoir waste management and agricultural practices through creating pathogen-free, eco-friendly fertilizers to promote both agricultural and environmental sustainability.

In artemisinin-resistant falciparum malaria parasites, mitochondrial metabolic pathways are essential for survival but not those of apicoplast

Emergence and spread of parasite resistance to artemisinins, the first-line antimalarial therapy, threaten the malaria eradication policy. To identify therapeutic targets to eliminate artemisinin-resistant parasites, the functioning of the apicoplast and the mitochondrion was studied, focusing on the fatty acid synthesis type II (FASII) pathway in the apicoplast and the electron transfer chain in the mitochondrion. A significant enrichment of the FASII pathway among the up-regulated genes in artemisinin-resistant parasites under dihydroartemisinin treatment was found, in agreement with published transcriptomic data. However, using GC-MS analyzes of fatty acids, we demonstrated for the first time that the FASII pathway is non-functional, ruling out the use of FASII inhibitors to target artemisinin-resistant parasites. Conversely, by assessing the modulation of the oxygen consumption rate, we evidenced that mitochondrial respiration remains functional and flexible in artemisinin-resistant parasites and even at the quiescent stage. Two novel compounds targeting electron transport chain (ELQ300, ELQ400) efficiently killed quiescent artemisinin-resistant parasites. Therefore, mitochondrial respiration represents a key target for the elimination of artemisinin-resistant persistent Plasmodium falciparum parasites.

Co-infection of Liburna oophaga sp. nov. and Ikanecator primus on cuttlefish (Sepia pharaonis) eggs and the effectiveness of peracetic acid as a treatment

The cuttlefish Sepia pharaonis species complex is emerging as a promising set of organisms for research in neuroscience, the behavioral sciences, and commercial aquaculture. At the same time, information about pathogens and diseases that could affect cuttlefish cultivation in intensive aquaculture settings remains limited. Our study has identified two species of parasite, the protozoan Liburna oophaga sp. nov. and the metazoan Ikanecator primus, that co-infect cuttlefish eggs, increasing mortality and reducing hatching rates. L. oophaga sp. nov. is reported here for the first time to enhance mortality during the incubation period by inducing deformity in cuttlefish eggs. We investigated the application of peracetic acid to parasite elimination during cuttlefish egg incubation. When cuttlefish eggs were treated with a peracetic acid containing product (PAA-product); 35 mg/L PAA + 15 mg/L H2O2, L. oophaga on the surfaces of the eggs were eliminated within 10 min. PAA-product; 70 mg/L PAA + 30 mg/L H2O2 was required to achieve the same effect for I. primus. Immersion treatment with PAA-product at 70 mg/L PAA + 30 mg/L H2O2 reduced parasitic load and improved survival of cuttlefish embryos and hatchling size, demonstrating that PAA product can inhibit and control parasitic co-infections in cephalopod culture.

Anti-Leishmania amazonensis Activity of Morolic Acid, a Pentacyclic Triterpene with Effects on Innate Immune Response during Macrophage Infection.

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.

In Vivo Bioluminescence Imaging Reveals Differences in Leishmania infantum Parasite Killing Kinetics by Antileishmanial Reference Drugs.

The bioluminescent Leishmania infantum BALB/c mouse model was used to evaluate the parasiticidal drug action kinetics of the reference drugs miltefosine, paromomycin, sodium stibogluconate, and liposomal amphotericin B. Infected mice were treated for 5 days starting from 7 days post-infection, and parasite burdens were monitored over time via bioluminescence imaging (BLI). Using nonlinear regression analyses of the BLI signal, the parasite elimination half-life (t1/2) in the liver, bone marrow, and whole body was determined and compared for the different treatment regimens. Significant differences in parasiticidal kinetics were recorded. A single intravenous dose of 0.5 mg/kg liposomal amphotericin B was the fastest acting with a t1/2 of less than 1 day. Intraperitoneal injection of paromomycin at 320 mg/kg for 5 days proved to be the slowest with a t1/2 of about 5 days in the liver and 16 days in the bone marrow. To conclude, evaluation of the cidal kinetics of the different antileishmanial reference drugs revealed striking differences in their parasite elimination half-lives. This BLI approach also enables an in-depth pharmacodynamic comparison between novel drug leads and may constitute an essential tool for the design of potential drug combinations.

Leishmania blood parasite dynamics during and after treatment of visceral leishmaniasis in Eastern Africa: A pharmacokinetic-pharmacodynamic model.

With the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is crucial to improving treatment efficacy and predicting patient relapse in cases of VL. This study aimed to characterize the kinetics of circulating Leishmania parasites in the blood, during and after different antileishmanial therapies, and to find predictors for clinical relapse of disease. Data from three clinical trials, in which Eastern African VL patients received various antileishmanial regimens, were combined in this study. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during, and up to six months after treatment. An integrated population pharmacokinetic-pharmacodynamic model was developed using non-linear mixed effects modelling. Parasite proliferation was best described by an exponential growth model, with an in vivo parasite doubling time of 7.8 days (RSE 12%). Parasite killing by fexinidazole, liposomal amphotericin B, sodium stibogluconate, and miltefosine was best described by linear models directly relating drug concentrations to the parasite elimination rate. After treatment, parasite growth was assumed to be suppressed by the host immune system, described by an Emax model driven by the time after treatment. No predictors for the high variability in onset and magnitude of the immune response could be identified. Model-based individual predictions of blood parasite load on Day 28 and Day 56 after start of treatment were predictive for clinical relapse of disease. This semi-mechanistic pharmacokinetic-pharmacodynamic model adequately captured the blood parasite dynamics during and after treatment, and revealed that high blood parasite loads on Day 28 and Day 56 after start of treatment are an early indication for VL relapse, which could be a useful biomarker to assess treatment efficacy of a treatment regimen in a clinical trial setting.

Resolving the polycistronic aftermath: Essential role of topoisomerase IA in preventing R-loops in Leishmania

Kinetoplastid parasites are ‘living bridges’ in the evolution from prokaryotes to higher eukaryotes. The near-intronless genome of the kinetoplastid Leishmania, exhibit polycistronic transcription which can facilitate R-loop formation. Therefore, to prevent such DNA-RNA hybrids Leishmania has retained prokaryotic-like DNA Topoisomerase IA (LdTOPIA) in course of evolution. LdTOPIA is an essential enzyme which is expressed ubiquitously and is adapted for the compartmentalized eukaryotic form in harboring functional bipartite nuclear localization signals. Although exhibiting greater homology to mycobacterial TOPIA, LdTOPIA could functionally complement the growth lethality of E. coli TOPIA null GyrB ts strain at non-permissive temperatures. Purified LdTOPIA exhibits, Mg2+ dependent relaxation of only negatively supercoiled DNA and preference towards single-stranded DNA substrates. LdTOPIA prevent nuclear R-loops as conditional LdTOPIA downregulated parasites exhibit R-loop formation and thereby parasite killing. The clinically used tricyclic antidepressant, norclomipramine could specifically inhibit LdTOPIA and lead to R-loop formation and parasite elimination. This comprehensive study therefore paves an avenue for drug repurposing against Leishmania.

An overpressure monitoring system based on PVDF integrated Electronic sensor with enhanced noise attenuation capability

The measurement of shockwave overpressure is of great significance for the safe use of explosives. The traditional overpressure monitoring systems are based on Integrated Electronics Piezo-Electric (IEPE) ceramic sensors. However, the brittleness of piezoelectric ceramic limits the application of overpressure monitoring system in high impact overpressure testing. Herein, a novel overpressure monitoring system based on Integrated Electronic Poly (vinylidene fluoride) (PVDF) (PFIE) sensor with electromagnetic interference shielding capability and parasitic vibration noise elimination function was designed for intense overpressure acquiring. PVDF, as a polymer, can endure much higher impact pressures compared to piezoelectric ceramics. However, its larger internal resistance makes it more prone to electromagnetic interference. To address this, an electromagnetic shielding structure was designed, incorporating an impedance matching circuit that effectively reduces the sensor's output impedance. Additionally, to mitigate excessive vibration noise during overpressure testing, the differential noise reduction technique has been implemented. Both the laboratory testing and the real blast testing with 10 kg trinitrotoluene were performed to validate the PFIE overpressure monitoring system. The result shows that the electromagnetic noise suppression ability of the PFIE overpressure sensors developed for the monitoring system was improved by 45 dB, and the parasitic vibration noise could be attenuated from 30 % to 1 %, what’s more the RMS errors of the overpressure dynamic parameters obtained by the monitoring system were below 10 %. This work has successfully addressed the noise sensitivity issue inherent in PVDF when used as a pressure sensor, capitalizing on its robust impact resistance. This approach has provided a viable solution for measuring overpressure in scenarios involving intense shock pressures, leveraging the strengths of PVDF in such demanding applications.

Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis.

Insects have specialized cell types that participate in the elimination of parasites, for instance, the lamellocytes of the broadly studied species Drosophila melanogaster. Other drosophilids, such as Drosophila ananassae and the invasive Zaprionus indianus, have multinucleated giant hemocytes, a syncytium of blood cells that participate in the encapsulation of the eggs or larvae of parasitoid wasps. These cells can be formed by the fusion of hemocytes in circulation or originate from the lymph gland. Their ultrastructure highly resembles that of the mammalian megakaryocytes. Morphological, protein expressional, and functional features of blood cells were revealed using epifluorescence and confocal microscopy. The respective hemocyte subpopulations were identified using monoclonal antibodies in indirect immunofluorescence assays. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were used in phagocytosis tests. Gene expression analysis was performed following mRNA sequencing of blood cells. D. ananassae and Z. indianus encapsulate foreign particles with the involvement of multinucleated giant hemocytes and mount a highly efficient immune response against parasitoid wasps. Morphological, protein expressional, and functional assays of Z. indianus blood cells suggested that these cells could be derived from large plasmatocytes, a unique cell type developing specifically after parasitoid wasp infection. Transcriptomic analysis of blood cells, isolated from naïve and wasp-infected Z. indianus larvae, revealed several differentially expressed genes involved in signal transduction, cell movements, encapsulation of foreign targets, energy production, and melanization, suggesting their role in the anti-parasitoid response. A large number of genes that encode proteins associated with coagulation and wound healing, such as phenoloxidase activity factor-like proteins, fibrinogen-related proteins, lectins, and proteins involved in the differentiation and function of platelets, were constitutively expressed. The remarkable ultrastructural similarities between giant hemocytes and mammalian megakaryocytes, and presence of platelets, and giant cell-derived anucleated fragments at wound sites hint at the involvement of this cell subpopulation in wound healing processes, in addition to participation in the encapsulation reaction. Our observations provide insights into the broad repertoire of blood cell functions required for efficient defense reactions to maintain the homeostasis of the organism. The analysis of the differentiation and function of multinucleated giant hemocytes gives an insight into the diversification of the immune mechanisms.

Transdermal antimalarial drug delivery to improve poor adherence to antimalarials: A new light at the end of the tunnel

Malaria, a perilous disease caused by Plasmodium parasites and characterized by a substantial mortality rate, has persistently posed as a global health challenge. Conventional antimalarial formulations, although effective, grapple with issues surrounding their bioavailability and palatability, and potentially hampering patient adherence and inadvertently fueling drug resistance and poor treatment outcomes. This paper meticulously delves into the predicaments associated with prevailing antimalarial delivery methods – oral, intravenous, and intramuscular. The paper navigates through the compelling merits of the transdermal pathway, drawing inspiration from its triumphant deployment in other medical realms. The investigation extends to encompass preclinical inquiries dedicated to exploring the transdermal administration of antimalarials. Transdermal antimalarials have shown complete suppression and elimination of Plasmodium parasites, as suggested by the preclinical studies. These preclinical studies emerge as a beacon of hope, exhibiting heightened bioavailability, enhanced safety margins, and notable cost-effectiveness when compared with oral antimalarials. Moreover, this innovative avenue for drug delivery not only offers convenience but also holds the potential to be a transformative solution to the adherence problems of traditional antimalarials, which currently afflicts standard therapeutic options.

Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model.

Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.

Babesia negevi infection in dogs and response to treatment

Canine babesiosis is an important protozoan tick-borne disease associated with anemia and thrombocytopenia and caused by several different Babesia spp. Babesia negevi was first reported to infect dogs in the Middle East in 2020. This study describes the presentation, clinical signs, parasitemia levels quantified by molecular techniques, laboratory findings and treatment of dogs infected with B. negevi following the first description of this species. Clinical findings in the infected dogs, a 3-year old female and two 8-week old male and female pups, included extreme lethargy and pale mucous membranes, anemia and thrombocytopenia found in all three animals. Fever was present in the older female and icterus in the female pup. Babesia parasites resembling B. negevi were detected by microscopy of blood smears from the dogs. PCR of blood targeting the 18S rRNA and cox1 genes confirmed that babesiosis was caused by B. negevi and PCR targeting the Borrelia flagellin gene indicated co-infection with Borrelia persica in two dogs. Treatment of the dogs with imidocarb dipropionate resulted in clinical improvement and initial decrease in the B. negevi parasite load as detected by quantitative PCR in two dogs, however the female pup continued to deteriorate and died. The parasite load in the 3-year old female decreased from 43,451 parasites/µl blood pre-imidocarb dipropionate treatment to 803 parasites/µl within two weeks. In the surviving pup, it decreased from 3,293,538 parasites/µl pre-treatment to 20,092 parasites/µl after two weeks. Babesia negevi DNA was still recovered from blood samples by PCR despite repeated treatment with imidocarb dipropionate one-month post-treatment in the surviving pup and up to seven months post-treatment in the 3-year old female. Only treatment with atovaquone and azithromycin for ten days eliminated B. negevi in both dogs as confirmed by negative PCR two weeks later. In conclusion, treatment with imidocarb dipropionate was helpful for recovery from clinical disease but did not facilitate parasite elimination, and it is therefore recommended to treat canine B. negevi infection with the combination of atovaquone and azithromycin.

Numerical assessment of the impact of hemozoin on the dynamics of a within-host malaria model

Phagocytosis of infected red blood cells by macrophages can lead to the elimination of malaria parasites. However, the phagocytic function of macrophages can be diminished when they ingest the malarial pigment called hemozoin. In this study, we consider an in-host malaria model which assesses the impact of the ingestion or uptake of hemozoin by macrophages on the dynamics of malaria in a human host. It is shown that the model undergoes the backward bifurcation phenomenon. This phenomenon is induced by the suppression or inhibition of the phagocytic function of macrophages resulting from their interaction with hemozoin. More so, it is shown numerically that the model can undergo a Hopf bifurcation with periodic solutions appearing in all compartments of the model when the suppression rate of the phagocytic function of macrophages by hemozoin is sufficiently small.

Importance of nanorobots in pharma and medical field

Machines built at the molecular level (referred to as "nanomachines") may be utilized to treat the human body of its numerous diseases. Nanorobotics is the science of building machines or robots at or near the scale of a nanometre (10-9 meters). Nanomedicine is the term used to describe this application of nanotechnology to the field of medicine. Future-looking uses for nanotechnology include minuscule robots that can build other machines, navigate inside the body to distribute drugs, or do microsurgery. Chemists are discovering how to use protein dynamics to power micro and nano size machines using catalytic processes, drawing inspiration from the biological motors of live cells. The toolkit for nanorobots includes items like a cavity for storing medication, probes, blades, and chisels to remove plaque and obstructions, microwave emitters, and ultrasonic signal generators to destroy cancerous cells, two electrodes generating an electric current, heating the cell up until it dies, powerful lasers could burn away harmful material like arterial plaque. A cream incorporating nanorobots that remove the proper amount of dead skin, remove excess oils, add missing oils, apply the right amounts of natural moisturizing ingredients, and even accomplish the elusive objective of "deep pore cleaning" may be utilized to treat skin problems. Other uses include the treatment of gout, kidney stones, gouty arthritis, parasite elimination, cancer treatment, and arteriosclerosis treatment.

Persistent Biofluid Small-Molecule Alterations Induced by Trypanosoma cruzi Infection Are Not Restored by Parasite Elimination.

Chagas disease (CD), caused by Trypanosoma cruzi (T. cruzi) protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome of T. cruzi-infected mice via liquid chromatography tandem mass spectrometry of clinically accessible biofluids: saliva, urine, and plasma. Urine was the most indicative of infection status across mouse and parasite genotypes. Metabolites perturbed by infection in urine include kynurenate, acylcarnitines, and threonylcarbamoyladenosine. Based on these results, we sought to implement urine as a tool for the assessment of CD treatment success. Strikingly, it was found that mice with parasite clearance following benznidazole antiparasitic treatment had an overall urine metabolome comparable to that of mice that failed to clear parasites. These results provide a complementary hypothesis to explain clinical trial data in which benznidazole treatment did not improve patient outcomes in late-stage disease, even in patients with successful parasite clearance. Overall, this study provides insights into new small-molecule-based CD diagnostic methods and a new approach to assess functional responses to treatment.

First molecular data on the human roundworm Ascaris lumbricoides species complex from the Bronze and Iron Age in Hallstatt, Austria

Palaeoparasitological studies can provide valuable information on the emergence, distribution, and elimination of parasites during a particular time in the past. In the prehistoric salt mines of Hallstatt, located in the Austrian Alps, human faeces have been conserved in salt. The aim of this study was to recover ancient DNA of intestinal parasites from these coprolites. Altogether, 35 coprolites from the Hallstatt salt mines, dating back to the Bronze Age mining phase (1158–1063 BCE) and the Iron Age mining phase (750–662 BCE), respectively, were analysed by microscopy and molecular methods. In 91% of the coprolite samples, eggs of soil-transmitted helminths (STH), namely of Trichuris and/or Ascaris were detected by light microscopy. The Ascaris eggs were exceptionally well preserved. For further analysis, DNA was extracted from the palaeofaecal samples and species-specific primers targeting different genes were designed. While amplification of Trichuris DNA remained unsuccessful, sequence data of A. lumbricoides species complex were successfully obtained from 16 coprolites from three different genes, the mitochondrial cytochrome c oxidase subunit 1 gene (cox1), the mitochondrial cytochrome B gene (cytB) and the mitochondrial NADH dehydrogenase subunit 1 gene (nadh1). Importantly, these included two Ascaris sequences from a coprolite from the Bronze Age, which to the best of our knowledge are the first molecular data of this genus from this period.

Artemisinin reduces acute ovarian ischemia-reperfusion injury in rats

Artemisinin (ARS) is well known as an effective agent in the treatment of malaria through the rapid elimination of Plasmodium falciparum parasites. This study aims to investigate the effect of ARS in treating adnexal torsion, one of the most common gynecological surgical emergencies. ARS was administered intraperitoneally once 30 min before unilateral ovarian torsion in two different doses (10 mg/kg vs. 50 mg/kg). Torsion was maintained for 3 h and then held in the detorted state for 3 h. Bilateral adnexectomy was performed to measure antioxidant enzyme activities and oxidant levels on the ipsilateral ovary and to make histopathological and immunohistochemical analyses on the contralateral ovary. Ischemia-reperfusion (I/R) injury dramatically upregulated the activities of CAT, GST, and MDA levels in the ipsilateral ovary, which were all downregulated by ARS treatment. A significant increase in follicular cell degeneration, congestion, and edema in the contralateral ovary was seen in the I/R group, which was significantly reduced with ARS treatment. Furthermore, I/R injury resulted in a significant increase in apoptosis as shown by the increased levels of BAX and CASP-3, and decreased levels of BCL-2 whereas ARS significantly reduced the impact of the injury. Our data, based on a rat I/R injury model, show that both ipsilateral and contralateral ovaries are protected with ARS pretreatment, and 50 mg/kg ARS treatment demonstrates to be more effective than the 10 mg/kg ARS.

Current prevalence and geographic distribution of helminth infections in the parasitic endemic areas of rural Northeastern Thailand

BackgroundHelminth infection is a global health issue that not only causes acute helminthiasis but long-term infection may lead to complicated symptoms as well as severe complications. The World Health Organization cooperated with the Ministry of Public Health in many countries, particularly where high prevalence, spending a lot of resources for limiting the infection. In Thailand, the incidence of parasitic helminth infections was continuously declined in the last few decades according to several campaigns for parasitic elimination. However, the rural community in the northeast of Thailand where the highest prevalence of the country still needs to be monitored. This present study aims to report the current prevalence of parasitic helminth infections in Nakhon Ratchasima and Chaiyaphum provinces where sharing a huge area of the northeastern region of Thailand but only a few studies have been published.MethodsThe stool specimens were collected from 11,196 volunteers and processed by modified Kato-Katz thick smear, PBS-ethyl acetate concentration techniques, and PCR. The epidemiological data were collected, analyzed, and used for generating of parasitic hotspots.ResultsThe results indicated that O. viverrini remains the major parasite in this area with a total prevalence of 5.05% followed by Taenia spp., Hookworms, T. trichiura, and Echinostoma spp., respectively. Mueang district of Chaiyaphum province has the highest prevalence especially O. viverrini with a prevalence of 7.15% that higher than the latest national surveillance. Interestingly, the prevalence of O. viverrini was hugely reported (more than 10%) in five subdistricts. The geographic localization of O. viverrini infections revealed that a lot of water reservoirs such as the lakes or branches of the river in the two-most prevalent subdistricts. Our finding indicated that gender and age were insignificantly different.ConclusionThis finding suggested that the parasitic helminth infection in the rural areas of northeast of Thailand remains high and the housing location is a major contributing factor for the parasitic infection.