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1.
Exp Parasitol ; 213: 107887, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32224062

RESUMO

Infection with trematodes produces physiological and behavioural changes in intermediate snail hosts. One response to infection is parasitic castration, in which energy required for reproduction of the host is thought to be redirected to promote development and multiplication of the parasite. This study investigated some reproductive and biochemical parameters in the nervous (CNS) and ovotestis (OT) tissues of Biomphalaria alexandrina during the course of Schistosoma mansoni infection. Antioxidant and oxidative stress parameters including catalase (CAT), nitric oxide (NO) and lipid peroxidation (MDA) were measured. Levels of steroid hormones, including testosterone, progesterone and estradiol, were also assessed. Finally, flow cytometry was used to compare measures of apoptosis between control snails and those shedding cercariae by examining mitochondrial membrane potential with the stain 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) and poly(ADP-ribose) polymerase (PARP). Infection with S. mansoni caused a 47.7% reduction in the net reproductive rate (Ro) of B. alexandrina. CAT activity was increased in the CNS at 21 days post infection (dpi) but by 28 dpi it was reduced below control values. Also, CAT activity increased significantly in the OT at 14, 21 and 28 dpi. In CNS tissues, NO levels were reduced at 7 dpi, increased at 14 and 21 dpi, and reduced again at 28 dpi. The overall level of lipid peroxidation gradually increased during the course of infection to reach its highest levels at 28 dpi. Steroid hormone measurements showed that concentrations of testosterone and estradiol were reduced in the CNS tissues at 28 dpi, while those of progesterone were slightly increased in the CNS and OT tissues. The percentage of cells that positively stained with JC-1was significantly increased in CNS and OT tissues of infected snails while the percentage of cells positively stained with PARP was decreased compared to controls. Together, these findings indicate that infection initiates diverse biochemical and hormonal changes leading to loss of cells responsible for egg laying and reproduction in B. alexandrina.


Assuntos
Biomphalaria/parasitologia , Interações Hospedeiro-Parasita , Schistosoma mansoni/fisiologia , Animais , Cercárias/fisiologia , Gônadas/parasitologia , Sistema Nervoso/parasitologia
2.
PLoS Negl Trop Dis ; 14(4): e0007951, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32240157

RESUMO

Schistosomes are parasitic blood flukes that infect >200 million people around the world. Free-swimming larval stages penetrate the skin, invade a blood vessel, and migrate through the heart and lungs to the vasculature of the liver, where maturation and mating occurs. From here, the parasite couples migrate to their preferred egg laying sites. Here, we compare and contrast what is known about the migration patterns within the definitive host of the three major species of human schistosome: Schistosoma mansoni, S. japonicum, and S. haematobium. We conclude that intravascular schistosomes are inexorable colonizers whose migration and egg laying strategy is profligate; all three species (and their eggs) can be found throughout the mesenteric venules, the rectal venous plexus, and, to a greater or lesser extent, the urogenital venous plexuses. In addition, it is common for parasite eggs to be deposited in locations that lack easy access to the exterior, further demonstrating the relentless exploratory nature of these intravascular worms.


Assuntos
Vasos Sanguíneos/parasitologia , Locomoção , Schistosoma haematobium/fisiologia , Schistosoma japonicum/fisiologia , Schistosoma mansoni/fisiologia , Animais , Humanos , Estágios do Ciclo de Vida , Esquistossomose Urinária/parasitologia , Esquistossomose Japônica/parasitologia , Esquistossomose mansoni/parasitologia
3.
PLoS One ; 15(2): e0228007, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32107485

RESUMO

BACKGROUND: Schistosomiasis is one of the most neglected tropical parasitic disease which is common in Ethiopia. It is disease of rural areas for decades but now days there are reports of schistosomiasis from urban settings. Therefore, this study aimed to determine epidemiology of Schistosoma mansoni (S. mansoni) infection and associated determinant factors among school children attending primary schools nearby rivers in Jimma town, an urban setting, southwest Ethiopia. METHODOLOGY: A cross sectional study was conducted among 328 school children aged between 7-17 years in selected primary schools nearby rivers in Jimma town from March to April 2017. For the diagnosis of S. mansoni, a single stool sample was obtained from each child and processed using double Kato Katz thick smear for quantification of S. mansoni ova examined using light microscope. A questionnaire was used to collect socio demographic data and associated determinant factors for S. mansoni infection. Data were analyzed using SPSS version 20.0. Variables with P-value < 0.05 were significantly associated with S. mansoni infection. RESULTS: The overall prevalence of S. mansoni infection was found to be 28.7%. Majority of infection intensities were categorized as light with maximum egg per gram of stool (epg) was 1728. The geometric mean of infection intensity was 102.3epg. Schools distance from river (p = 0.001), swimming habit in rivers (p = 0.001) and crossing river on bare foot (p = 0.001) were independent risk factors for S. mansoni infection. CONCLUSIONS: The study revealed S. mansoni infection is prevalent in Jimma town. The school children were at moderate risk of morbidity caused by S. mansoni (prevalence ≥ 10% and < 50% according to WHO threshold), hence a biannual mass drug administration with praziquantel is required once every two years in the study area and promote health information on prevention, control, transmission and risk factors for S. mansoni infection.


Assuntos
Rios , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/parasitologia , Instituições Acadêmicas , Estudantes , Animais , Criança , Cidades/epidemiologia , Etiópia/epidemiologia , Análise Fatorial , Feminino , Humanos , Masculino , Análise Multivariada , Prevalência , Fatores de Risco
4.
Nat Med ; 26(3): 326-332, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066978

RESUMO

Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas1. Novel medicines and vaccines are urgently needed2,3. An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3-10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4+ T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.


Assuntos
Antiparasitários/uso terapêutico , Modelos Biológicos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Vacinas/imunologia , Adolescente , Adulto , Animais , Antígenos de Helmintos/sangue , Antígenos de Helmintos/imunologia , Antiparasitários/farmacologia , Citocinas/sangue , Feminino , Humanos , Imunidade Humoral/efeitos dos fármacos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/sangue , Esquistossomose mansoni/microbiologia , Adulto Jovem
5.
PLoS Negl Trop Dis ; 14(2): e0007875, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32084128

RESUMO

BACKGROUND: Clinical observations and animal studies have suggested that Salmonella intestinal carriage is promoted by concurrent Schistosoma infection. The present study assessed association of Salmonella intestinal carriage and Schistosoma mansoni infection among individuals in a Schistosoma endemic area in sub-Saharan Africa. METHODS: From November 2015 to March 2016, a cross-sectional community-wide study was conducted in Kifua II, a rural village in Kongo Central Province, Democratic Republic of Congo. Stool samples were collected and analyzed for Salmonella intestinal carriage (culture) and Schistosoma mansoni infection (Kato Katz microscopy with determination of egg load). Salmonella Typhimurium and Enteritidis isolates were assessed for genetic similarity with blood culture isolates obtained during the same period in a neighboring hospital using multi-locus variable-numbers tandem repeat analysis (MLVA). RESULTS: A total of 1,108 participants were included (median age 15 years (IQR: 7-36), male-to-female ratio of 1:1.1). The overall prevalence of Schistosoma mansoni infection and non-typhoidal Salmonella carriage was 51.2% (95% CI: 48.2-54.1) and 3.4% (95% CI: 2.5-4.7) respectively, with 2.2% (95% CI: 1.5-3.2) of participants coinfected. The proportion of Salmonella carriage tended to be higher among Schistosoma mansoni infected participants compared to non-infected participants but this difference did not reach statistical significance (4.2% versus 2.6%, p = 0.132). However, the proportion of Salmonella carriage among participants with a heavy Schistosoma mansoni infection was significantly higher compared to those with a light and moderate infection (8.7% versus 3.2%, p = 0.012) and compared to Schistosoma mansoni negatives (8.7% versus 2.6%, p = 0.002). The 38 Salmonella isolates comprised five and four Enteritidis and Typhimurium serotypes respectively, the majority of them had MLVA types identical or similar to those observed among blood culture isolates. CONCLUSION: Salmonella intestinal carriage was associated with a heavy intensity of Schistosoma mansoni infection. Further studies are needed to address causation.


Assuntos
Portador Sadio/microbiologia , Intestinos/microbiologia , Salmonella typhimurium/isolamento & purificação , Esquistossomose mansoni/parasitologia , Adolescente , Adulto , Animais , Portador Sadio/epidemiologia , Criança , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Estudos Transversais , República Democrática do Congo/epidemiologia , Feminino , Humanos , Masculino , População Rural , Salmonella typhimurium/genética , Schistosoma mansoni/genética , Schistosoma mansoni/isolamento & purificação , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/epidemiologia , Adulto Jovem
6.
Proc Biol Sci ; 287(1919): 20192446, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31964301

RESUMO

Resource availability can powerfully influence host-parasite interactions. However, we currently lack a mechanistic framework to predict how resource fluctuations alter individual infection dynamics. We address this gap with experiments manipulating resource supply and starvation for a human parasite, Schistosoma mansoni, and its snail intermediate host to test a hypothesis derived from mechanistic energy budget theory: resource fluctuations should reduce schistosome reproduction and virulence by inhibiting parasite ingestion of host biomass. Low resource supply caused hosts to remain small, reproduce less and produce fewer human-infectious cercariae. Periodic starvation also inhibited cercarial production and prevented infection-induced castration. The periodic starvation experiment also revealed substantial differences in fit between two bioenergetic model variants, which differ in their representation of host starvation. Simulations using the best-fit parameters of the winning model suggest that schistosome performance substantially declines with resource fluctuations with periods greater than 7 days. These experiments strengthen mechanistic theory, which can be readily scaled up to the population level to understand key feedbacks between resources, host population dynamics, parasitism and control interventions. Integrating resources with other environmental drivers of disease in an explicit bioenergetic framework could ultimately yield mechanistic predictions for many disease systems.


Assuntos
Schistosoma mansoni/fisiologia , Caramujos/parasitologia , Animais , Interações Hospedeiro-Parasita , Humanos , Recursos Naturais , Parasitos
7.
Exp Parasitol ; 208: 107793, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31711973

RESUMO

Praziquantel (PZQ) is the sole drug used to treat schistosomiasis, and the probability of developing resistance is growing the longer it is relied upon, justifying the search for alternatives. Phosphodiesterases (PDEs), particularly the PDE4 family, have attracted considerable attention as drug targets, including in Schistosoma mansoni, and especially SmPDE4A. This study investigates the potential antischistosomal activity of human PDE4 and potent SmPDE4A inhibitor roflumilast, either alone or combined with PZQ. In vitro, roflumilast resulted in a significant, concentration-dependent reduction in egg production but not of worm viability. In vitro exposure to roflumilast in combination with a low concentration of PZQ was less effective than PZQ alone, pointing to antagonism. S. mansoni-infected mice treated with roflumilast showed significant reductions in worm burden (27%) as well as hepatic and intestinal egg burdens (~28%) two weeks post treatment. Scanning EM of worms isolated from roflumilast-treated and untreated mice did not reveal noticeable changes to their tegument. S. mansoni-infected mice treated with a fixed dosage of roflumilast and a variable dosage of PZQ resulted in a higher reduction in worm burden, reduced hepatic egg counts, absence of immature eggs and a marked increase in dead eggs, compared to PZQ alone. However, the combination resulted in increased animal mortality, probably attributable to pharmacodynamic interactions between the two drugs. Although this study marks the first report of in vivo antischistosomal potential by a PDE inhibitor, an important proof of concept, we conclude that the antischistosomal effects of roflumilast are insufficient to warrant further development.


Assuntos
Aminopiridinas/farmacologia , Anti-Helmínticos/farmacologia , Benzamidas/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/efeitos dos fármacos , Ciclopropanos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Concentração Inibidora 50 , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Oviposição/efeitos dos fármacos , Praziquantel/farmacologia , Schistosoma mansoni/enzimologia , Schistosoma mansoni/fisiologia , Schistosoma mansoni/ultraestrutura
8.
Exp Parasitol ; 208: 107779, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31634474

RESUMO

Here, we report enhanced the in vitro effect of potassium usnate on coupled adult Schistosoma mansoni worms at different time intervals and concentrations. The evaluated schistosomicidal parameters were the following: motility, mortality, fecundity and integumentary changes, as viewed in photomicrographs. Potassium usnate was able to cause 100 and 50% mortality at 100 and 50 µM concentrations, respectively, after 24 h of exposure, while 25 and 12.5 µM concentrations caused changes in motility at 48 and 72 h, and lethality at 96 and 120 h respectively. Eggs were not detected at any of the concentrations analyzed. Photomicrographs revealed morphological tegument alterations within all periods of observation, such as swelling, blisters, dorsoventral contraction, short and curved worms. In conclusion, our results indicate that potassium usnate represents a possible candidate for a new drug in the control of schistosomiasis.


Assuntos
Anti-Helmínticos/farmacologia , Benzofuranos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/prevenção & controle , Análise de Variância , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/química , Benzofuranos/administração & dosagem , Benzofuranos/química , Relação Dose-Resposta a Droga , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Movimento/efeitos dos fármacos , Fotomicrografia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/tratamento farmacológico , Fatores de Tempo
9.
Elife ; 82019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31845890

RESUMO

Human disease agents exist within complex environments that have underappreciated effects on transmission, especially for parasites with multi-host life cycles. We examined the impact of multiple host and parasite species on transmission of the human parasite Schistosoma mansoni in Kenya. We show S. mansoni is impacted by cattle and wild vertebrates because of their role in supporting trematode parasites, the larvae of which have antagonistic interactions with S. mansoni in their shared Biomphalaria vector snails. We discovered the abundant cattle trematode, Calicophoron sukari, fails to develop in Biomphalaria pfeifferi unless S. mansoni larvae are present in the same snail. Further development of S. mansoni is subsequently prevented by C. sukari's presence. Modeling indicated that removal of C. sukari would increase S. mansoni-infected snails by two-fold. Predictable exploitation of aquatic habitats by humans and their cattle enable C. sukari to exploit S. mansoni, thereby limiting transmission of this human pathogen.


Assuntos
Biomphalaria/parasitologia , Interações Hospedeiro-Parasita , Parasitos/fisiologia , Esquistossomose/transmissão , Animais , Biodiversidade , Bovinos , Humanos , Quênia/epidemiologia , Modelos Biológicos , Schistosoma mansoni/fisiologia , Esquistossomose/epidemiologia , Trematódeos/fisiologia
10.
PLoS One ; 14(11): e0225425, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31765429

RESUMO

Schistosomiasis is caused by a trematode of the genus Schistosoma and affects over 200 million people worldwide. The only drug recommended by the World Health Organization for treatment and control of schistosomiasis is praziquantel. Development of new drugs is therefore of great importance. Thiazoles are regarded as privileged structures with a broad spectrum of activities and are potential sources of new drug prototypes, since they can act through interactions with DNA and inhibition of DNA synthesis. In this context, we report the synthesis of a series of thiazole derivatives and their in vitro schistosomicidal activity by testing eight molecules (NJ03-08; NJ11-12) containing thiazole structures. Parameters such as motility and mortality, egg laying, pairing and parasite viability by ATP quantification, which were influenced by these compounds, were evaluated during the assays. Scanning electron microscopy (SEM) was utilized for evaluation of morphological changes in the tegument. Schistosomula and adult worms were treated in vitro with different concentrations (6.25 to 50 µM) of the thiazoles for up to 5 and 3 days, respectively. After in vitro treatment for five days with 6.25 µM NJ05 or NJ07 separately, we observed a decrease of 30% in schistosomula viability, whilst treatment with NJ05+NJ07 lead to a reduction of 75% in viability measured by ATP quantitation and propidium iodide labeling. Adult worms' treatment with 50 µM NJ05, NJ07 or NJ05 + NJ07 showed decreased motility to 30-50% compared with controls. Compound NJ05 was more effective than NJ07, and adult worm viability after three days was reduced to 25% in parasites treated with 50 µM NJ05, compared with a viability reduction to 40% with 50 µM NJ07. SEM analysis showed severe alterations in adult worms with formation of bulges and blisters throughout the dorsal region of parasites treated with NJ05 or NJ07. Oviposition was extremely affected by treatment with the NJ series compounds; at concentrations of 25 µM and 50 µM, oviposition reached almost zero with NJ05, NJ07 or NJ05 + NJ07 already at day one. Tested genes involved in egg biosynthesis were all confirmed by qPCR as downregulated in females treated with 25 µM NJ05 for 2 days, with a significant reduction in expression of p14, Tyrosinase 2, p48 and fs800. NJ05, NJ07 or NJ05+NJ07 treatment of HEK293 (human embryonic cell line) and HES (human epithelial cell line) showed EC50 in the range of 18.42 to 145.20 µM. Overall, our results demonstrate that those molecules are suitable targets for further development into new drugs for schistosomiasis treatment, although progress is needed to lessen the cytotoxic effects on human cells. According to the present study, thiazole derivatives have schistosomicidal activities and may be part of a possible new arsenal of compounds against schistosomiasis.


Assuntos
Anti-Helmínticos/toxicidade , Schistosoma mansoni/efeitos dos fármacos , Tiazóis/toxicidade , Animais , Anti-Helmínticos/síntese química , Feminino , Células HEK293 , Humanos , Masculino , Oviposição/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Tiazóis/síntese química
11.
Parasitol Res ; 118(12): 3519-3533, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673833

RESUMO

The main objective of this work is preparation of mesoporous silica nanoparticles loaded with praziquantel (PZQ-Si) in order to enhance the therapeutic efficacy of praziquantel (PZQ). Mice were experimentally infected with Schistosoma mansoni and treated 6 weeks post-infection with PZQ in different doses via either oral or intraperitoneal (IP) routes. PZQ in the same doses orally administered to S. mansoni-infected mice was used as a drug control, and infected and non-infected non-treated mice served as positive and negative controls, respectively. PZQ-Si exhibited good physicochemical attributes in terms of small uniform size (105 nm), spherical shape, and PZQ entrapment efficiency (83%). A maximum antischistosomal effect was achieved using orally administered PZQ-Si as reflected by total worm burden, tissue egg count, oogram pattern, and hepatic granuloma count and diameter. The biomarkers related to liver oxidative stress status and immunomodulatory effect (serum TNF-α and IL-10) were significantly improved. Data obtained implied that IP route was less efficacious for the delivery of PZQ-Si. Encapsulation of PZQ permits the reduction of the used therapeutic dose of PZQ. Hepatic DNA fragmentation, measured by comet assay, was significantly improved in infected mice treated with maximum dose of PZQ-Si as compared to positive or PZQ control groups. The results indicate that mesoporous silica NP is a promising safe nanocarrier for PZQ potentiating its antischistosomal, antioxidant, immunomodulatory, and anti-inflammatory action in animal model infected with S. mansoni. From a practical standpoint, PZQ-Si using a lower dose of PZQ could be suggested for effective PZQ antischistosomal mass chemotherapy.


Assuntos
Anti-Helmínticos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Praziquantel/administração & dosagem , Esquistossomose mansoni/tratamento farmacológico , Animais , Anti-Helmínticos/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Modelos Animais de Doenças , Humanos , Fígado/parasitologia , Masculino , Camundongos , Nanopartículas/química , Praziquantel/química , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Dióxido de Silício/química
12.
Parasit Vectors ; 12(1): 485, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619284

RESUMO

BACKGROUND: Parasite traits associated with transmission success, such as the number of infective stages released from the host, are expected to be optimized by natural selection. However, in the trematode parasite Schistosoma mansoni, a key transmission trait, i.e. the number of cercariae larvae shed from infected Biomphalaria spp. snails, varies significantly within and between different parasite populations and selection experiments demonstrate that this variation has a strong genetic basis. In this study, we compared the transmission strategies of two laboratory schistosome population and their consequences for their snail host. METHODS: We infected inbred Biomphalaria glabrata snails using two S. mansoni parasite populations (SmBRE and SmLE), both isolated from Brazil and maintained in the laboratory for decades. We compared life history traits of these two parasite populations by quantifying sporocyst growth within infected snails (assayed using qPCR), output of cercaria larvae and impact on snail host physiological response (i.e. hemoglobin rate, laccase-like activity) and survival. RESULTS: We identified striking differences in virulence and transmission between the two studied parasite populations. SmBRE (low shedder (LS) parasite population) sheds very low numbers of cercariae and causes minimal impact on the snail physiological response (i.e. laccase-like activity, hemoglobin rate and snail survival). In contrast, SmLE (high shedder (HS) parasite population) sheds 8-fold more cercariae (mean ± SE cercariae per shedding: 284 ± 19 vs 2352 ± 113), causes high snail mortality and has strong impact on snail physiology. We found that HS sporocysts grow more rapidly inside the snail host, comprising up to 60% of cells within infected snails, compared to LS sporocysts, which comprised up to 31%. Cercarial production is strongly correlated to the number of S. mansoni sporocyst cells present within the snail host tissue, although the proportion of sporocyst cells alone does not explain the low cercarial shedding of SmBRE. CONCLUSIONS: We demonstrated the existence of alternative transmission strategies in the S. mansoni parasite consistent with trade-offs between parasite transmission and host survival: a "boom-bust" strategy characterized by high virulence, high transmission and short duration infections and a "slow and steady" strategy with low virulence, low transmission but long duration of snail host infections.


Assuntos
Biomphalaria/parasitologia , Schistosoma mansoni/fisiologia , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/transmissão , Animais , Biomphalaria/fisiologia , Brasil , Cercárias , Estudos de Coortes , Cricetinae , DNA de Helmintos/química , DNA de Helmintos/isolamento & purificação , Vetores de Doenças , Feminino , Hemoglobinas/análise , Hemolinfa/química , Hemolinfa/enzimologia , Humanos , Lacase/análise , Masculino , Mesocricetus , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase em Tempo Real , Schistosoma mansoni/crescimento & desenvolvimento , Razão de Masculinidade , Virulência
13.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(4): 362-367, 2019 Sep 19.
Artigo em Chinês | MEDLINE | ID: mdl-31612669

RESUMO

OBJECTIVE: To compare the difference of fertility of Biomphalaria glabrata snails between self-fertilization and cross-fertilization and to observe the circadian rhythm of laying eggs, the effect of light on laying eggs and the tolerance of the snail to water and food deficiency, so as to provide the evidence for control and elimination of B. glabrata snails in the field. METHODS: Under laboratory conditions, a single B. glabrata egg for self-fertilization was separated and hatched individually, and young snails were raised in different plastic boxes individually. The eggs for cross-fertilization were hatched and the young snails were fed in the same plastic box. The ability of spawn, the development of the eggs, and the number of snails growing from young to adult snails were compared between the self-fertilization and cross-fertilization. The snails were in the water under four environments, all day illumination, all day without illumination, daytime lighting and night without illumination, and daytime without illumination but night lighting. The eggs were collected and counted daily. The circadian rhythm of spawn and the effect of illumination on spawn were observed. The adult snails were divided into 6 groups and exposed to the environments with relative humidity of 0, 65%, 87% and 100%, respectively. The survival rates of the adult snails exposed to the different environments after different time were observed. The adult snails were placed at 25 °C in the oven to remove water content from the soft body of snails. When the dehydration rates of the soft bodies achieved 10%, 20%, 30%, 40%, 50%, 52%, 55%, 57%, 60%, and 70% respectively, the survival rates of the adult snails exposed to the oven were observed. RESULTS: In the 25 °C water, the average laying egg number for 15 days per snail was (8.77 ± 16.92) eggs/snail in the self-fertilization snail. The average laying egg number for 15 days per snail was (149.71 ± 142.28) eggs/snail in the cross-fertilization snails. There was a significant difference between the self-fertilization snail and cross-fertilization snail (t = 0.999 999, P < 0.01). The hatching rate and reproductive maturation rate of the self-fertilization snails and cross-fertilization snails were 50.1% and 78.9%, and 19.3% and 3.8%, respectively, There was a significant difference (the hatching rate: χ2 = 18.18, P < 0.01, the reproductive maturation rate: χ2 = 11.83, P < 0.01) . In the natural environment of daytime with illumination and nighttime with darkness, the amount of laying 20 eggs of B. glabrata snail was (944.07 ± 392.53) eggs/day during a whole day, among them the amount of laying eggs during daytime account for 10.1% and the amount of laying eggs during nighttime account for 89.9%, and the laying egg was given priority to with the night. The above results suggested that the dark environment was conducive to B. glabrata snails to lay eggs. The above results suggested that light can promote the increase of spawning of B. glabrata. When B. glabrata was exposed to the environments with the relative humidity of 0, 65%, 87% and 100% at 25 °C, respectively, and the longest survival times of snails were 7, 70, 150 d and 100 d, respectively. In the 25 °C water, the snails could survive for 50 days without food. The adult snails were placed at 25 °C in the oven to remove water content from the soft body of snails. When the dehydration rates of the soft bodies achieved 10%, 20%, 30%, 40%, 50%, 52%, 55%, 57%, 60%, and 70% respectively, the survival rates of the adult snails exposed to the oven were 100%, 100%, 100%, 100%, 70%, 30%, 0, 0, 0 and 0, respectively. CONCLUSIONS: B. glabrata can achieve the reproductive process by cross-fertilization or self-fertilization. There is a significant difference in reproductive ability between the cross-fertilization snail and self-fertilization snail, cross-fertilization is stronger than self-fertilization, but the rate of reproduction in the self-fertilization is higher than that in the cross-fertilization. It is indicated that B. glabrata that survive after the dry season plays an important role in the maintenance of local snail populations and transmission of schistosomiasis mansoni.


Assuntos
Biomphalaria , Interações Hospedeiro-Parasita , Schistosoma mansoni , Animais , Biomphalaria/parasitologia , Interações Hospedeiro-Parasita/fisiologia , Estágios do Ciclo de Vida/fisiologia , Reprodução , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/transmissão , Estações do Ano
14.
J Parasitol ; 105(4): 576-579, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31414948

RESUMO

Albino strains of Biomphalaria glabrata that are compatible with Schistosoma mansoni are commonly used to investigate snail-schistosome interactions, but whether they are all equally compatible is not known. In this study, compatibility with the Naval Medical Research Institute (NMRI) strain of S. mansoni was compared among 3 widely used albino strains: NMRI (the normal laboratory host for NMRI S. mansoni), M line, and University of Massachusetts Lowell (UML). Compatibility was assessed on the basis of infection prevalence following exposure to miracidia, the histological fate of sporocysts, and mitotic response in the snail amebocyte-producing organ (APO), a component of the internal defense system (IDS). Infection prevalence in UML was nearly identical to that in NMRI but was significantly lower in M line. Although the APO of UML showed no response to infection over the course of 9 days, mitotic activity was elevated in the APO of NMRI and M line, with that in M line being higher and more prolonged than in the APO of resistant BS-90 snails. Finally, hemocyte responses against some small primary sporocysts occurred at 1 and 3 days post-exposure (DPE) in all 3 strains, but in 2 of 5 M line a response also occurred against large primary sporocysts at 6 DPE. Thus, based on infection prevalence and tissue responses, compatibility with NMRI S. mansoni is lowest in M line, whereas UML and NMRI show the same degree of compatibility, despite decades of maintenance of this parasite strain in NMRI snails. The elevated mitotic response in the APO of M line and NMRI snails suggests that a response of the IDS can occur even in a compatible host-parasite relationship.


Assuntos
Biomphalaria/parasitologia , Vetores de Doenças/classificação , Schistosoma mansoni/fisiologia , Animais , Biomphalaria/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/transmissão
15.
BMC Res Notes ; 12(1): 447, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331397

RESUMO

OBJECTIVE: The aim of this study was to determine the magnitude of Schistosoma mansoni and its associated risk factors in the study area. RESULTS: Of 422 school children, 223 (52.8%) and 199 (47.2%) were males and females, respectively. The Overall prevalence of Schistosoma mansoni infection was 24.9% (105/422). Seventy-five out of 422 (71.4%) of the infected individuals showed light infections. The overall mean intensity of Schistosoma mansoni in the study was 106.16 eggs per gram of stool. Age (p = 0.013), swimming habit (p = 0.001), participating in irrigational activities (p = 0.03) and washing clothes in the river (p = 0.039) were factors associated with Schistosoma mansoni infection.


Assuntos
Fezes/parasitologia , População Rural/estatística & dados numéricos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Adolescente , Animais , Criança , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Esquistossomose mansoni/epidemiologia , Instituições Acadêmicas
16.
Exp Parasitol ; 203: 30-35, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31150655

RESUMO

Schistosoma mansoni adult worms are extensively challenged by reactive oxygen species from intrinsic sources. However, the effects of extrinsic sources such as ethanol have not been looked at in schistosomes. We examined adult worms recovered from ethanol-consuming mice by light (LM), confocal (CM) and scanning electron microscopy (SEM) to address this question. Schistosomiasis-infected mice were orally gavaged with 18% (v/v) ethanol from 35 to 63 days post-infection, when they were euthanized. CM examination revealed reduced germ cells density (-36%, p = 0.0001) and sperm density (-58%, p = 0.0001) in testicular lobes, and immature cells in seminal vesicle compared to unexposed control worms. Female worms showed reduced density of vitellin glands (-71%, p = 0.0001), maturation of oocytes (-7%, p = 0.0071) and reduced spermatozoa density (-23%, p = 0.0002) within the seminal receptacle. SEM revealed remarkable damages in male's tegument, including tubercles flattening, tegumental peeling and erosive lesions. Given that lipids are present in reproductive system and tegument, our results suggest that phenotypic changes are due to ethanol-induced lipid peroxidation. To the best of our knowledge, this is the first report revealing the biological action of ethanol intake on adult schistosomes in vivo.


Assuntos
Etanol/administração & dosagem , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/parasitologia , Administração Oral , Animais , Etanol/toxicidade , Feminino , Genitália/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Veias Mesentéricas/parasitologia , Camundongos , Microscopia Confocal , Microscopia Eletrônica de Varredura , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Sistema Porta/parasitologia , Reprodução/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Schistosoma mansoni/ultraestrutura
17.
Int J Parasitol ; 49(8): 647-656, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31170410

RESUMO

Adult schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, have always been considered to be homolactic fermenters and, in their energy metabolism, strictly dependent on carbohydrates. However, more recent studies suggested that fatty acid ß-oxidation is essential for egg production by adult female Schistosoma mansoni. To address this conundrum, we performed a comprehensive study on the lipid metabolism of S. mansoni. Incubations with [14C]-labelled fatty acids demonstrated that adults, eggs and miracidia of S. mansoni did not oxidise fatty acids, as no 14CO2 production could be detected. We then re-examined the S. mansoni genome using the genes known to be involved in fatty acid oxidation in six eukaryotic model reference species. This showed that the earlier automatically annotated genes for fatty acid oxidation were in fact incorrectly annotated. In a further analysis we could not detect any genes encoding ß-oxidation enzymes, which demonstrates that S. mansoni cannot use this pathway in any of its lifecycle stages. The same was true for Schistosoma japonicum and all other schistosome species that have been sequenced. Absence of ß-oxidation, however, does not imply that fatty acids from the host are not metabolised by schistosomes. Adult schistosomes can use and modify fatty acids from their host for biosynthetic purposes and incorporate those in phospholipids and neutral lipids. Female worms deposit large amounts of these lipids in the eggs they produce, which explains why interference with the lipid metabolism in females will disturb egg formation, even though fatty acid ß-oxidation does not occur in schistosomes. Our analyses of S. mansoni further revealed that during the development and maturation of the miracidium inside the egg, changes in lipid composition occur which indicate that fatty acids deposited in the egg by the female worm are used for phospholipid biosynthesis required for membrane formation in the developing miracidium.


Assuntos
Ácidos Graxos/metabolismo , Schistosoma mansoni/metabolismo , Animais , Dióxido de Carbono/metabolismo , Cricetinae , Código de Barras de DNA Taxonômico , Metabolismo Energético , Feminino , Proteínas de Helminto/genética , Proteínas de Helminto/fisiologia , Metabolismo dos Lipídeos , Lipidômica , Mesocricetus , Óvulo/fisiologia , Oxirredução , Schistosoma mansoni/enzimologia , Schistosoma mansoni/fisiologia
18.
Integr Comp Biol ; 59(5): 1243-1252, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120514

RESUMO

The consequences of parasite infection for individual hosts depend on key features of host-parasite ecology underpinning parasite growth and immune defense, such as age, sex, resource supply, and environmental stressors. Scaling these features and their underlying mechanisms from the individual host is challenging but necessary, as they shape parasite transmission at the population level. Translating individual-level mechanisms across scales could inherently improve the way we think about feedbacks among parasitism, the mechanisms driving transmission, and the consequences of human impact and disease control efforts. Here, we use individual-based models (IBMs) based on general metabolic theory, Dynamic Energy Budget (DEB) theory, to scale explicit life-history features of individual hosts, such as growth, reproduction, parasite production, and death, to parasite transmission at the population level over a range of resource supplies focusing on the major human parasite, Schistosoma mansoni, and its intermediate host snail, Biomphalaria glabrata. At the individual level, infected hosts produce fewer parasites at lower resources as competition increases. At the population level, our DEB-IBM predicts brief, but intense parasite peaks early during the host growth season when resources are abundant and infected hosts are few. The timing of these peaks challenges the status quo that high densities of infected hosts produce the highest parasite densities. As expected, high resource supply boosts parasite output, but parasite output also peaks at modest to high host background mortality rates, which parallels overcompensation in stage-structured models. Our combined results reveal the crucial role of individual-level physiology in identifying how environmental conditions, time of the year, and key feedbacks within host-parasite ecology interact to define periods of elevated risk. The testable forecasts from this physiologically-explicit epidemiological model can inform disease management to reduce human risk of schistosome infection.


Assuntos
Biomphalaria/parasitologia , Metabolismo Energético , Interações Hospedeiro-Parasita , Schistosoma mansoni/fisiologia , Animais , Humanos , Densidade Demográfica
19.
J R Soc Interface ; 16(150): 20180675, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30958153

RESUMO

Schistosomiasis is a chronic and morbid disease of poverty affecting approximately 200 million people worldwide. Mature schistosome flatworms wander in the host's hepatic portal and mesenteric venous system where they encounter a range of blood flow conditions and geometrical confinement. However, the mechanisms that support schistosome locomotion and underlie the pathogen's adaptation to its physical environment are largely unknown. By combining microfabrication and traction force microscopy, we developed various in vitro assays to quantify the mechanics of locomotion of adult male Schistosoma mansoni in different physiologically relevant conditions. We show that in unconfined settings, the parasite undergoes two-anchor marching mediated by the coordinated action of its oral and ventral suckers. This mode of locomotion is maintained when the worm faces an external flow, to which it responds by adjusting the strength of its suckers. In geometrically confined conditions, S. mansoni switches to a different crawling modality by generating retrograde peristaltic waves along its body, a mechanism shared with terrestrial and marine worms. However, while the surface of most worms has backward-pointing bristles that rectify peristaltic waves and facilitate forward locomotion, S. mansoni has isotropically oriented tubercles. This requires tight coordination between muscle contraction and substrate friction but gives S. mansoni the ability to reverse its direction of locomotion without turning its body, which is likely advantageous to manoeuvre in narrow-bore vessels. We show that the parasite can also coordinate the action of its suckers with its peristaltic body contractions to increase crawling speed. Throughout this study, we report on a number of biomechanical parameters to quantify the motility of adult schistosomes (e.g. sucker grabbing strength, the rate of detachment under flow, peristaltic wave properties and traction stresses). The new series of in vitro assays make it possible to quantify key phenotypical aspects of S. mansoni motility that could guide the discovery of new drugs to treat schistosomiasis.


Assuntos
Locomoção/fisiologia , Modelos Biológicos , Schistosoma mansoni/fisiologia , Animais , Masculino
20.
PLoS Negl Trop Dis ; 13(3): e0007240, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30870428

RESUMO

Natural products have moved into the spotlight as possible sources for new drugs in the treatment of helminth infections including schistosomiasis. Surprisingly, insect-derived compounds have largely been neglected so far in the search for novel anthelminthics, despite the generally recognized high potential of insect biotechnology for drug discovery. This motivated us to assess the antischistosomal capacity of harmonine, an antimicrobial alkaloid from the harlequin ladybird Harmonia axyridis that raised high interest in insect biotechnology in recent years. We observed remarkably pleiotropic effects of harmonine on physiological, cellular, and molecular processes in adult male and female Schistosoma mansoni at concentrations as low as 5 µM in vitro. This included tegumental damage, gut dilatation, dysplasia of gonads, a complete stop of egg production at 10 µM, and increased production of abnormally shaped eggs at 5 µM. Motility was reduced with an EC50 of 8.8 µM and lethal effects occurred at 10-20 µM within 3 days of culture. Enzyme inhibition assays revealed acetylcholinesterase (AChE) as one potential target of harmonine. To assess possible effects on stem cells, which represent attractive anthelminthic targets, we developed a novel in silico 3D reconstruction of gonads based on confocal laser scanning microscopy of worms after EdU incorporation to allow for quantification of proliferating stem cells per organ. Harmonine significantly reduced the number of proliferating stem cells in testes, ovaries, and also the number of proliferating parenchymal neoblasts. This was further supported by a downregulated expression of the stem cell markers nanos-1 and nanos-2 in harmonine-treated worms revealed by quantitative real-time PCR. Our data demonstrate a multifaceted antischistosomal activity of the lady beetle-derived compound harmonine, and suggest AChE and stem cell genes as possible targets. Harmonine is the first animal-derived alkaloid detected to have antischistosomal capacity. This study highlights the potential of exploiting insects as a source for the discovery of anthelminthics.


Assuntos
Alcenos/farmacologia , Anti-Helmínticos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Alcenos/isolamento & purificação , Animais , Anti-Helmínticos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Besouros/química , Feminino , Masculino , Testes de Sensibilidade Parasitária , Reprodução/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Células-Tronco/efeitos dos fármacos , Análise de Sobrevida
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