Trypanosoma cruzi Parasite Load Modulates the Circadian Activity Pattern of Triatoma infestans

American trypanosomiasis is a disease caused by the flagellate protozoan Trypanosoma cruzi, which is transmitted mainly in endemic areas by blood-sucking triatomine vectors. Triatoma infestans is the most important vector in the southern cone of South America, exhibiting a nocturnal host-seeking behavior. It has been previously documented that the parasite produces changes in some triatomine species, but this is the first time that the behavior of a vector has been evaluated in relation to its parasite load. After comparing the movement events and distance traveled of infected and non-infected T. infestans, we evaluated the change produced by different T. cruzi parasite loads on its circadian locomotor activity. We observed differences between infected and non-infected triatomines, and a significant relation between the parasite load and the increase in locomotor activity of T. infestans, which was accentuated during the photophase. This could have direct implications on the transmission of T. cruzi, as the increased movement and distance traveled could enhance the contact of the vector with the host, while increasing the predation risk for the vector, which could both constitute a risk for vectorial and oral transmission to mammals.

Specific Recognition of β-Galactofuranose-Containing Glycans of Synthetic Neoglycoproteins by Sera of Chronic Chagas Disease Patients

Chagas disease (CD) can be accurately diagnosed by detecting Trypanosoma cruzi in patients’ blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method’s limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages. Nevertheless, these stages also abundantly express cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and glycoinositolphospholipids (GIPLs) bearing nonreducing terminal β-galactofuranosyl (β-Galf) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients’ sera react specifically with synthetic β-Galf-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of T. cruzi GIPL-derived Galfβ1,3Manpα-(CH2)3SH (glycan G29SH) and Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα-(CH2)3SH (glycan G32SH); and (b) preparation of neoglycoproteins NGP29b and NGP32b, and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that NGP32b can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα is an immunodominant glycotope and that NGP32b could potentially be used as a novel CCD biomarker.

Neuroimaging Findings in Racemose Neurocysticercosis: Case Description and Literature Review

Neurocysticercosis (NCC), the most common central nervous system (CNS) parasitic infection among the immunocompetent population can imitate every clinical feature of brain-diseases accurately, drawing attention away from the real culprit and delaying the proper treatment. There are two types of NCC, the parenchymal and the extraparenchymal form. The extraparenchymal NCC include the ventricular cysticercosis, the subarachnoid cysts including giant cysts or racemose cysticercosis with chronic meningitis, the spinal (intra- or extramedullary) cysticercosis and the ophthalmic cysticercosis. It is estimated that about 30% of epilepsy cases in endemic countries are due to NCC and especially the racemose NCC is more aggressive and associated with higher mortality rates. There is a significant heterogeneity in clinical phenotypes, regarding the racemose NCC, which depends on the parasite load and evolutionary stage in association with its location in CNS and the host’s immune response. Crucial for the management of the racemose NCC is the early recognition of the symptoms and the swift initiation of antiparasitic therapy with anti-inflammatory agents in combination with the shunt-insertion in cases of obstructive hydrocephalus. In view of the former considerations we conducted a narrative literature review on racemose NCC and described the diagnostic challenges of a relevant case that we had evaluated in our Department of Neurology.

PARA UMA DOENÇA TÃO ANTIGA, O VISLUMBRE DE NOVOS TRATAMENTOS PROMISSORES NA DOENÇA DE CHAGAS

It has been more than 100 years since the discovery of Chagas Disease (CD). However, the repertoire indicated for its treatment is still limited. Thus, this article aims to present a review of the new pharmacological strategies being studied for CD. This literature review, consisting of 68 articles, from 1957 to 2021, was carried out on several scientific platforms. Positive effects from benznidazole have been described in the acute and chronic phases, in addition to its association with itraconazole in the acute phase. Among the cruzain inhibitors, the compound K777 presented trypanocidal effects, although demonstrating major adverse effects, while its analogue WRR-483 demonstrated great beneficial effects in vivo and in vitro. As for the nitroheterocyclics, fexinidazole showed high rates of cure in animal model, in addition to low toxicity. Nifurtimox, in early chronic stages, was able to delay the progression of tissue damage and reduce the parasite load. The compound WC-9, a squalene synthase inhibitor, showed potential inhibition of T. cruzi replication. Regarding aromatic diamidines, many compounds were able to stop the trypanosome, both in vitro and in vivo models. It was concluded that there are favorable findings to improve the treatment of CD. However, the development of effective new drugs does not only depend on their effective action, but also on numerous variables that must be circumvented, such as the reduction of side effects, treatment time and adherence to the current medication of choice, as well as the investment in production and distribution to the population.

Sexual and developmental variations of ecto-parasitism in damselflies

The prevalence and intensity of parasitism can have different fitness costs between sexes, and across species and developmental stages. This variation could arise because of species specific sexual and developmental differences in body condition, immunity, and resistance. Theory predicts that the prevalence of parasitism will be greater in individuals with poor body condition and the intensity of parasitism will be greater in individuals with larger body size. These predictions have been tested and verified in vertebrates. In insects, however, contradictory evidence has been found in different taxa. Here, we tested these predictions on two species of Agriocnemis (Agriocnemis femina and Agriocnemis pygmaea) damselflies, which are parasitized by Arrenurus water mite ectoparasites. We measured body weight, total body length, abdomen area and thorax area of non-parasitized damselflies and found body condition varied between males and females, between immature females and mature females and between A. femina and A. pygmaea. Then, we calculated the parasite prevalence, i.e., the frequency of parasitism and intensity, i.e., the number of parasites per infected damselfly in eleven natural populations of both species. In line to our predictions, we observed greater prevalence in immature females than mature females but found no difference in parasite prevalence between males and females. Furthermore, we found that parasite load was higher in females than males and in immature females than mature females. Our result also showed that the frequency and intensity of parasitism varied between the two studied species, being higher in A. pygmaea than A. femina. Our study provides evidence that parasitism impacts sexes, developmental stages and species differentially and suggests that variation may occur due to sex, developmental stage, and species-specific resistance and tolerance mechanism.

Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi

Background Kra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype. Methods Kra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections during acute and chronic infections. Results As expected, the kra monkeys controlled acute infections and remained with low-level, persistent parasitaemias without anti-malarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopenia, and moderate to severe anaemia. Mathematical modelling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low. Conclusions Kra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3–5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.

Wildfires modify the parasite loads of invasive cane toads

The frequency and severity of wildfires are increasing due to anthropogenic modifications to habitats and to climate. Post-fire landscapes may advantage invasive species via multiple mechanisms, including changes to host–parasite interactions. We surveyed the incidence of endoparasitic lungworms ( Rhabdias pseudosphaerocephala ) in invasive cane toads ( Rhinella marina ) in near-coastal sites of eastern Australia, a year after extensive fires in this region. Both the prevalence of infection and number of worms in infected toads increased with toad body size in unburned areas. By contrast, parasite load decreased with toad body size in burned areas. By killing moisture-dependent free-living lungworm larvae, the intense fires may have liberated adult cane toads from a parasite that can substantially reduce the viability of its host. Smaller toads, which are restricted to moist environments, did not receive this benefit from fires.

Pregnant dairy goats endoparasites reduced by commercial Homeopathy

Background: the endoparasitosis affects dairy goats in worldwide distribution. This impacts the economical activity and implies in eminent risk of animal looses by helminths blood depletion (Nogueira, 2010). Resistance to all therapeutic drugs is reported, the parasitism implies to elevation of production costs, toxic residues in milk and environment, frequently monitoring of ocular mucosa and healthy status (Cavalcanti, 2007; Silva, 2010). Many publications reports Fecal Eggs Count (FEC) FEC reduction in sheeps with homeopathy (Chagas, 2008; Zacharias 2008; Neves, 2012; Falbo, 2013). This work continues the study of previous assessment with young females caprines, but now during the breeding season and multipara pregnants. The under field conditions intends to address the value of this complex medicine in the real life situation of a caprinoculture routine and the animal zootechnical production phases. Aims: this work determined the parasite load by FEC during the periods of breeding season and pregnancy of dairy goats with commercial populational homeopathy. Methodology: Fifteen (15) adult multipara goats (CAPRA AERGICUS HIRCUS) aged 4.4 ± 1.4 years old were randomly enrolled into two groups. The animals has dairy predominance of Alpine and Saanen breeds and were fed by maize and sugar cane silage. Routine measures to reduce the natural parasitism infection included keeping them in elevated houses with slatted floor with access to paddock star grass with time restrictions to the hottest hours in the day. They received the albendazole antihelmintic drenching before each of the phases. The weekly FEC was performed in triplicate with the McMaster Egg Counting Chamber Technique and the optical microscope. The treatment with 10g-animal-day CapriOvi Verm 100 RealH (Brazil) was given daily among both phases, six times a week with individual oral administration, the powder was diluted (not sucussed) in a plastic cup with tap water and given in a 10mL syringe. The control group received only tap water in the same way but brand new separated set of disposable materials. Each phase had evaluating period of 10 and 11 weeks respectively. The first phase has the four weeks breeding season, previously stimulated by light program, with sex mating on the middle and the second phase the animals was pregnant for 2 to 4 months. Results: The FEC kept above 500 eggs during 7 weeks at the breeding season-1st phase but grew as expected in the pregnancy-2nd phase. The FEC was significantly reduced during the 2nd phase (p-value < 0.01) but not in the breeding season-1st phase (p-value = 0.28), despite being lower than the control. The two-way ANOVA showed that treatment in the 2nd phase affected the results [F 1/143 = 9.04, p = 0.0031] as the time does [F 1/143 = 53.29, p < 0.0001]: there were interactions between factors [F 1/143 = 3.15, p = 0.0011]. The two-way ANOVA showed that treatment in the 1nd phase affected the results [F 1/130 = 0.30, p = 0.58] as the time [F 1/130 = 1.24, p = 0.28]: there were no interactions between factors [F 1/130 = 0.58, p = 0.81]. Surprisingly there was absence of growing FEC in the breeding season, at this phase the dry goats and may have better immune response to the endoparasites than the stress of the pregnancy. Our group suppose the stressed animal model is more susceptible and may show better the effects of treatment reducing the FEC in a high challenge situation. How it influences the way of action of ultra high dilutions remains a very interesting question for guide future works. Conclusion: the populational homeopathy product CapriOvi Verm 100 RealH has shown the reduction of the FEC during the pregnancy of dairy goats.

Skeleton binding protein-1-mediated parasite sequestration inhibits spontaneous resolution of malaria-associated acute respiratory distress syndrome

Malaria is a hazardous disease caused by Plasmodium parasites and often results in lethal complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Parasite sequestration in the microvasculature is often observed, but its role in malaria pathogenesis and complications is still incompletely understood. We used skeleton binding protein-1 (SBP-1) KO parasites to study the role of sequestration in experimental MA-ARDS. The sequestration-deficiency of these SBP-1 KO parasites was confirmed with bioluminescence imaging and by measuring parasite accumulation in the lungs with RT-qPCR. The SBP-1 KO parasites induced similar lung pathology in the early stage of experimental MA-ARDS compared to wildtype (WT) parasites. Strikingly, the lung pathology resolved subsequently in more than 60% of the SBP-1 KO infected mice, resulting in prolonged survival despite the continuous presence of the parasite. This spontaneous disease resolution was associated with decreased inflammatory cytokine expression measured by RT-qPCR and lower expression of cytotoxic markers in pathogenic CD8+ T cells in the lungs of SBP-1 KO infected mice. These data suggest that SBP-1-mediated parasite sequestration and subsequent high parasite load are not essential for the development of experimental MA-ARDS but inhibit the resolution of the disease.

In vitro cytotoxic and leishmanicidal activity of isolated and semisynthetic ent-pimaranes from Aldama arenaria

Two pimaranes ent-pimara -8(14),15-dien-19-oic acid (1) and ent-8(14),15-pimaradien-3β-ol (2), isolated from Aldama arenaria, and six semi-synthetic derivatives methyl ester of the ent-pimara-8(14),15-dien-19-oic acid (3), ent-pimara-8(14),15-dien-19-ol (4), acetate of ent-pimara-8(14),15-dien-19-ol (5), ent-pimara-8(14),15-dien-19-ol succinic acid (6), acetate of ent-8(14),15-pimaradien-3β-ol (7), ent-8(14),15-pimaradien-3β-ol succinic acid (8) were evaluated in vitro for their cytotoxic activities to childhood leukemia cell lines and leishmanicidal activity against the parasite Leishmania amazonensis. Among these compounds, 1 to 6 presented moderate cytotoxic activity, with compound 4 being the most active (GI50 of 2.6 µM for the HL60 line) and the derivatives 7 and 8 inactive. Against the parasite Leishmania amazonensis, the most promising derivative was acetate of ent-pimara-8(14),15-dien-19-ol (5), with EC50 of 20.1 µM, selectivity index of 14.3, and significant reduction in the parasite load. Pimarane analogues 1, ent-pimara-8(14),15-dien-19-oic acid, and 2, ent-8(14),15-pimaradien-3β-ol, presented different activities, corroborating the application of such molecules as prototypes for the design of other derivatives that have greater cytotoxic or leishmanicidal potential.