RESUMEN
BACKGROUND: The prevalence of intestinal parasites is known to be high among Amerindian populations; further, there are serious problems in the healthcare of these populations in Brazil. The Maxakali, located in the northeastern region of Minas Gerais, Brazil, is an indigenous group that still preserves many of its cultural aspects. This study aimed to compare the positivity rate of schistosomiasis and soil-transmitted helminths in this ethnic group in epidemiological surveys conducted in 1972 and 2014. METHODS: Stool parasitological examinations were performed by the Kato-Katz technique during both periods in this population. In 2014, the parasitological diagnosis was also realized with the TF-Test® technique. RESULTS: In 1972, 270 inhabitants were examined. The positivity rates were 67.4% for Schistosoma mansoni, 72.9% for hookworms, 43.7% for Ascaris lumbricoides, and 23.7% for Trichuris trichiura. In 2014, 545 individuals were examined, and the positivity rates obtained were 45.7% for S. mansoni, 22.8% for hookworms, 0.6% for A. lumbricoides, and 2.8% for T. trichiura. CONCLUSIONS: The comparison of the parasitological surveys conducted in 1972 and 2014, indicates that the indigenous Maxakali remained neglected by the health and indigenous protection authorities during these four decades. The infection rate observed in 2014 for schistosomiasis and hookworm remains high, considering the current epidemiological view of these diseases in the Brazilian population.
Asunto(s)
Esquistosomiasis , Humanos , Brasil/epidemiología , Prevalencia , Estudios Transversales , Heces/parasitología , Esquistosomiasis/epidemiologíaRESUMEN
Rapid diagnostics provide actionable information for patient care at the time and site of an encounter with the health care system. The mainstay of infectious diseases care is early detection (case finding) and treatment completion, but for many, it is hard to identify positive individuals, as is the case of infection with low burden in schistosomiasis, a parasitic disease common in the tropics and subtropics. We developed a new, accurate, and fast Dot blot methodology (iDot) to indirectly detect Schistosoma mansoni in individuals with very low parasite burden using urine samples. Accuracy of 0.74 was obtained with a significant difference between negative and positive patients and a substantial agreement was found when iDot was compared with five available methods. Our analysis also revealed the superiority of iDot in detecting negative individuals from non-endemic sites, thus, presenting the lowest rate of false positives. This new method called iDot is convenient and suitable for qualitative and quantitative detection of schistosomiasis in individuals with low parasite burden.
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Esquistosomiasis mansoni , Esquistosomiasis , Animales , Antígenos Helmínticos , Heces , Humanos , Schistosoma mansoni , Esquistosomiasis mansoni/diagnóstico , Sensibilidad y EspecificidadRESUMEN
Imatinib, a drug used for treatment of human chronic myeloid leukaemia, due to its activity against protein kinases, has been also evaluated in vitro against Schistosoma mansoni showing high schistosomicidal activity. In the present experiments imatinib activity in vitro was confirmed at the doses of 25 µM, 50 µM and 100 µM. The first drug activity observed with the lower dose was interruption of egg-laying and with the higher dosages was the death of the worms. In mice infected with S. mansoni no activity was found even with 1,000 mg/kg/day, 500 mg/kg/day, single oral dose or when administered for three consecutive days. This is another example of the difference of results related to in vitro and in vivo trials using S. mansoni worms.
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Benzamidas/farmacología , Piperazinas/farmacología , Pirimidinas/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/farmacología , Animales , Relación Dosis-Respuesta a Droga , Mesilato de Imatinib , Ratones , Carga de Parásitos , Esquistosomiasis mansoni/parasitología , Factores de TiempoRESUMEN
Mice infected with Schistosoma mansoni were treated with oxamniquine, praziquantel, artesunate at the pre-patent phase, aiming at observing schistogram alterations. Half of the animals were perfused five days post-treatment for counting and classification of immature worms, based on pre-established morphological criteria (schistogram); the remaining animals were evaluated 42 or 100 days after infection and perfusion of the portal-system was performed for collection and counting of adult worms and oogram. It was observed that oxamniquine and artesunate treatment administered at the pre-postural phase causes significant reduction in the number of immature and adult worms. However, there was little reduction with praziquantel when used at the dose of 400 mg/kg for treatments administered 14, 15, 21 or 23 days post-infection. Artesunate was responsible for significant alterations in development of young worms, as well as for a higher number of worms presenting intestinal damages. Immature adult worms were detected in mice treated with artesunate or oxamniquine at the pre-patent phase of infection and recovered by perfusion 100 days after infection. Schistogram proved to be a very useful tool for experimental evaluation of the activity of antischistosomal drugs and a good model to identify the most sensitive stages to drugs.
Asunto(s)
Artemisininas/uso terapéutico , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéutico , Animales , Artesunato , Quimioterapia Combinada/métodos , Femenino , Ratones , Oxamniquina/uso terapéutico , Recuento de Huevos de Parásitos , Parasitemia/tratamiento farmacológico , Praziquantel/uso terapéutico , Schistosoma mansoni/crecimiento & desarrolloRESUMEN
Current schistosomiasis control strategies are largely based on chemotherapeutic agents and a limited number of drugs are available today. Praziquantel (PZQ) is the only drug currently used in schistosomiasis control programs. Unfortunately, this drug shows poor efficacy in patients during the earliest infection phases. The effects of PZQ appear to operate on the voltage-operated Ca2+ channels, which are located on the external Schistosoma mansoni membrane. Because some Ca2+ channels have dihydropyridine drug class (a class that includes nifedipine) sensitivity, an in vitro analysis using a calcium channel antagonist (clinically used for cardiovascular hypertension) was performed to determine the antischistosomal effects of nifedipine on schistosomula and adult worm cultures. Nifedipine demonstrated antischistosomal activity against schistosomula and significantly reduced viability at all of the concentrations used alone or in combination with PZQ. In contrast, PZQ did not show significant efficacy when used alone. Adult worms were also affected by nifedipine after a 24 h incubation and exhibited impaired motility, several lesions on the tegument and intense contractility. These data support the idea of Ca2+ channels subunits as drug targets and favour alternative therapeutic schemes when drug resistance has been reported. In this paper, strong arguments encouraging drug research are presented, with a focus on exploring schistosomal Ca2+ channels.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Nifedipino/farmacología , Praziquantel/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Animales , Ratones , Pruebas de Sensibilidad ParasitariaRESUMEN
BACKGROUND: The World Health Organization recommends a market-ready, urine-based point-of-care diagnostic test for circulating cathodic antigens (CCA) to determine the prevalence of S. mansoni. This study evaluated the performance of the URINE CCA (SCHISTO) ECO TESTE® (POC-ECO), which is currently available in Brazil. METHODS: Residents from eight sites with different prevalence estimates provided one urine sample for POC-ECO and one stool sample for Kato-Katz (KK) and Helmintex® (HTX) testing as an egg-detecting reference for infection status. RESULTS: None of the study sites had significantly higher POC-ECO accuracy than KK. CONCLUSIONS: POC-ECO is not currently recommended in Brazilian schistosomiasis elimination programs.
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Esquistosomiasis mansoni , Animales , Humanos , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/epidemiología , Schistosoma mansoni , Brasil/epidemiología , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Antígenos Helmínticos/orina , Prevalencia , HecesRESUMEN
The World Health Organization (WHO) recognizes schistosomiasis as one of the Neglected Tropical Diseases targeted for global elimination in the 2030 Agenda of the Sustainable Development Goals. In Brazil, schistosomiasis mansoni is considered a public health problem, particularly prevalent among vulnerable populations living in areas with poor environmental and sanitary conditions. In 2022, the WHO published a Guideline encompassing recommendations to assist national programs in endemic countries in achieving morbidity control, eliminating schistosomiasis as a public health problem, and advancing towards interrupting transmission. The perspectives presented here, collectively prepared by members of the Oswaldo Cruz Foundation's (Fiocruz) Schistosomiasis Translational Program (FioSchisto), along with invited experts, examine the feasibility of the WHO recommendations for the Brazilian settings, providing appropriate recommendations for public health policies applicable to the epidemiological reality of Brazil, and suggests future research to address relevant issues. In Brazil, the provision of safe water and sanitation should be the key action to achieve schistosomiasis elimination goals. The agencies involved in measures implementation should act together with the Primary Care teams for planning, executing, monitoring, and evaluating actions in priority municipalities based on their epidemiological indicators. Host snails control should prioritize judicious ecological interventions at breeding sites. The Information, Education, and Communication (IEC) strategy should be associated with water and sanitation and other control actions, actively involving school community. To identify infected carriers, FioSchisto recommends a two-stage approach of immunological and molecular tests to verify transmission interruption during the intervention and beyond. Praziquantel administration should be done under medical supervision at the Primary Care level. MDA should be considered in exceptional settings, as a measure of initial attack strategy in locations presenting high endemicity, always integrated with water and sanitation, IEC, and snail control. To assist decision-making, as well as the monitoring and evaluation of strategic actions, there is a need for an Information System. FioSchisto considers this systematization essential to make investments in strategic research to support the improvement of schistosomiasis control actions. Efforts toward schistosomiasis elimination in Brazil will succeed with a paradigm shift from the vertical prescriptive framework to a community-centered approach involving intersectoral and interdisciplinary collaboration.
Asunto(s)
Esquistosomiasis , Humanos , Brasil/epidemiología , Esquistosomiasis/epidemiología , Esquistosomiasis/prevención & control , Praziquantel , Organización Mundial de la Salud , AguaRESUMEN
BACKGROUND: The World Health Organization recommends reliable point-of-care (POC) diagnostic testing to eliminate schistosomiasis. Lateral flow immunoassay that detects schistosome circulating cathodic antigen (CCA) in urine to establish prevalence thresholds for intervention in endemic areas is recommended. Stored urine may be useful if surveying at-risk populations is delayed or interrupted by unforeseen circumstances, such as the current COVID-19 pandemic. This study evaluated the manufacturer's claim that Schistosoma mansoni infection can be reliably diagnosed in urine samples stored at -20°C for one year. METHODS: Two-hundred-forty-two subjects from an endemic site in Brazil provided one urine sample each for testing with URINE CCA (SCHISTO) ECO TESTE® (POC-ECO) and one stool sample each for testing with Kato-Katz (KK) and Helmintex® (HTX) as a robust reference standard for infection status. At least 2 ml of urine from each participant was stored at -20°C; after one year, 76 samples were randomly selected for POC-ECO retesting. RESULTS: The POC-ECO agreement between freshly collected and stored urine was inadequate considering trace results as positive (Cohen's kappa coefficient κ = 0.08) and negative (κ = 0.36). POC-ECO accuracy was not significantly greater than that of routine KK (54%; 95% confidence interval: 42.1%-65.5%). CONCLUSIONS: The precision and accuracy of POC-ECO have to be optimized in both freshly collected and stored urine before it can be recommended for use in control programs in Brazil.
Asunto(s)
COVID-19 , Esquistosomiasis mansoni , Animales , Antígenos Helmínticos/orina , Brasil/epidemiología , Heces , Humanos , Pandemias , Sistemas de Atención de Punto , Prevalencia , Reproducibilidad de los Resultados , SARS-CoV-2 , Schistosoma mansoni , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/epidemiología , Sensibilidad y EspecificidadRESUMEN
Praziquantel (PZQ) is the only drug available for community-based control programs which aim to reduce the prevalence and morbidity associated with schistosomiasis. Here, we synthesized and evaluated the schistosomicidal, biochemical and cytotoxic activities of EF24, a synthetic curcumin analog, against different isolates of Schistosoma mansoni. EF24 elicited marked phenotypic alterations at 10 µM against schistosomula and 42-day-old adult worms of the Naval Medical Research Institute (NMRI) isolate. EF24 had 50% effective concentration (EC50) values of <10 µM against the Luis Evangelista (LE), Sergipe (SE), Belo Horizonte (BH) and Belo Horizonte less sensitive to PZQ (BH < PZQ) isolates of adult S. mansoni; however, the respective sensitivities of these isolates differed. Changes in the parasite included, vacuolization of the tegument and focal lysis of the interstitial tissue and muscle layers. Against 28-day-old juvenile worms (LE isolate), EF24 was about three times more potent than PZQ. After 6 h at 12.5 µM, EF24 increased reactive oxygen species (ROS) and the activity of the antioxidant enzyme, glutathione-S-transferase (GST), by 32 and 19% in female and male adult worms, respectively. By contrast, after 6 h at 12.5 µM glutathione reductase (GR) activity decreased by 43 and 30%, and glutathione peroxidase (GPx) activity decreased by 67 and 44% in females and males, respectively. EF24 was less cytotoxic to mammalian host cells than to S. mansoni, with selectivity indexes (SIs) of 1.8-3.4 and 2.7-7.5 for juvenile and adult worms, respectively. Given the current evidence for the in vitro schistosomicidal effect of EF24, the structure-activity relationship of additional analogs to identify new candidates for schistosomiasis treatment is warranted.
Asunto(s)
Curcumina , Schistosoma mansoni , Esquistosomicidas , Animales , Femenino , Masculino , Antioxidantes/metabolismo , Curcumina/análogos & derivados , Curcumina/farmacología , Mamíferos , Praziquantel/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis/tratamiento farmacológico , Esquistosomicidas/farmacología , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Glutatión Reductasa/metabolismoRESUMEN
To elucidate the mechanisms of antischistosoma resistance, drug-resistant Schistosoma mansoni laboratory isolates are essential. We developed a new method for inducing resistance to praziquantel (PZQ) using successive drug treatments of Biomphalaria glabrata snails infected with S. mansoni. Infected B. glabrata were treated three times with 100 mg/kg PZQ for five consecutive days with a one-week interval between them. After the treatment, the cercariae (LE-PZQ) produced from these snails and the LE strains (susceptible) were used to infect mice. Forty-five days after infection, mice were treated with 200, 400 or 800 mg/kg PZQ. Thirty days post-treatment, we observed that the mean number of worms recovered by perfusion was significantly higher in the group of mice infected with the LE-PZQ isolate treated with 200 and 400 mg/kg in comparison to the LE strain with the same treatment. Moreover, there was a significant difference between the ED50 (effective dose required to kill 50% of the worms) of the LE-PZQ isolate (362 mg/kg) and the LE strain (68 mg/kg). In the in vitro assays, the worms of the LE-PZQ isolate were also less susceptible to PZQ. Thus, the use of infected snails as an experimental model for development of resistance to S. mansoni is effective, fast, simple and cheap.
Asunto(s)
Antihelmínticos/farmacología , Biomphalaria/parasitología , Resistencia a Medicamentos/efectos de los fármacos , Praziquantel/farmacología , Schistosoma mansoni/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Ratones , Pruebas de Sensibilidad ParasitariaRESUMEN
A point-of-care test for detecting schistosome circulating cathodic antigen in urine (POCCCA) has been proposed for mapping infection and defining prevalence thresholds for mass drug administration (MDA). However, there is increasing evidence that POCCCA may yield false-positive results, which requires rigorous specificity evaluation in non-endemic areas. POCCCA was applied in an area known to be free from infection and devoid of any condition for schistosomiasis transmission as part of a multicentre study to evaluate the performance of POCCCA in Brazil's low or potentially endemic settings. Besides POCCCA detection in urine, a search for eggs in stool was performed by Kato-Katz (KK) and Helmintex (HTX) methods. One-hundred-and-seventy-four participants returned urine samples, 140 of which delivered stool samples. All these were HTX-negative for Schistosoma mansoni, and all 118 tested with KK were negative for both S. mansoni and soil-transmitted helminths. POCCCA results from freshly collected urine yielded a specificity of 62.1% (95% CI: 53.6% - 70.2%), taking trace outcomes as positive according to the manufacturer's instructions. Retesting urine from the 140 HTX-negatives after one-year storage at -20 °C with two new POCCCA batches simultaneously yielded significantly different specificities (34.3%; 95%CI: 26.5% - 42.8% and 75.0%; 95% CI: 67.0% - 81.9%). These two batches had a weak agreement (Cohen's kappa: 0.56; 95%CI: 0.44-0.68) among the 174 urine samples retested. At present, POCCCA cannot be recommended either as a cut-off point for MDA or a reliable diagnostic tool for treatment of the infection carriers (selective chemotherapy) in low endemic areas and at final stages of transmission interruption. Manufacturers should be required to optimize production standardization and to assure quality and reproducibility of the test. Extended rigorous performance evaluations by different users from different regions are needed before POCCCA is widely recommended.
Asunto(s)
Antígenos Helmínticos/sangre , Pruebas en el Punto de Atención , Esquistosomiasis mansoni/sangre , Esquistosomiasis mansoni/diagnóstico , Adolescente , Animales , Brasil/epidemiología , Niño , Heces/parasitología , Femenino , Humanos , Masculino , Prevalencia , Reproducibilidad de los Resultados , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/inmunología , Sensibilidad y EspecificidadRESUMEN
The development of novel methods for parasitological diagnosis that are both highly sensitive and low in cost has been strongly recommended by the World Health Organization. In this study, a new technique for diagnosis of schistosomiasis mansoni is proposed based on the differential sedimentation of eggs when subjected to a slow continuous flux of 3% saline solution through a porous plaque. This influx suspends low-density faecal material, effectively cleaning the sample. The remaining sediment covering the porous plaque surface is then transferred to a glass slide and examined under a bright field microscope. Twelve Kato-Katz slides were used for comparison in the present study. Our results suggest that the saline gradient method detects a significantly higher number of eggs than the 12 Kato-Katz slides (p < 0.0001). We also found microscopic inspection to be quicker and easier with our newly described method. After cleaning the sample, the obtained sediment can also be conserved in a 10% formaldehyde solution and examined for at least 45 days later without statistically significant egg count differences.
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Heces/parasitología , Recuento de Huevos de Parásitos/métodos , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/diagnóstico , Cloruro de Sodio , Animales , Humanos , Recuento de Huevos de Parásitos/instrumentación , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Point of care tests would be valuable for field diagnosis. However, high sensitivity will likely be required in low endemicity sets where individuals with low schistosome burden are hard to diagnose. METHODS: Commercially available POC tests (POC-CCA® and Urine CCA (Schisto) ECO Teste®) were evaluated to evidence their potential in low endemicity areas. Individuals with 0-76 eggs per gram of feces were selected, and comparison was performed between Kato-Katz, Saline Gradient and POC-CCA® after urine concentration (POC FLT) methods. RESULTS: Both POC-CCA had poor performances, showing low identification of less than half of positive individuals and several undiagnosed cases, revealing an accuracy of 0.44 and 0.46, and a Kappa Index of 0.308 and 0, respectively. Positivity rates of POC-CCA tests were below the one found for a single Kato-Katz slide. POC FLT had a Kappa Index of 0.617, an accuracy of 0.81, 67% of reproducibility, and was shown to have the same sensitivity of 21 Kato-Katz slides when two tests were performed. CONCLUSIONS: POC-CCA® and POC Eco presented exactly the same inadequacy in low endemicity areas. POC FLT significantly improved the performance of POC-CCA®. More accurate methods must be evaluated in low endemicity areas.
Asunto(s)
Antígenos Helmínticos/orina , Glicoproteínas/orina , Proteínas del Helminto/orina , Pruebas en el Punto de Atención , Esquistosomiasis mansoni/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Toma de Decisiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
A prospective cohort study with rigorous searching for schistosomiasis cases was conducted among residents of Pedra Preta, Montes Claros, Minas Gerais State, Brazil, seven years after an intervention. Kato-Katz (KK), Saline Gradient, Miracidia Hatch and Polymerase Chain Reaction (PCR) were used as the diagnostic methods in 2008. In the period of 2013-2016, 175 patients remaining in the area were examined using the diagnostic methods Kato-Katz (24 slides, 1 g of feces) and Saline Gradient (2 procedures, 1 g of feces). Sixty-eight out of the 69 infected and treated individuals in 2008 tested negative. The percentage of new cases was 2.29% (4/175), and the 4 infected individuals presented low parasitic load [1, 6, 7 and 19 eggs per gram (EPG)]. All the participants answered epidemiological questionnaires on risky behavior. All residences had pit latrines and domiciliary water supply. The primary transmission focus (lake) was dry for several months. Malacological surveys showed a few non-infected specimens of Biomphalaria glabrata . A clear dominance of Biomphalaria straminea was observed. It can be inferred that a significant decrease in the disease transmission occurred after a single action through an intense search for infected and treated cases under the ecoepidemiological conditions of this area.
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Biomphalaria/parasitología , Praziquantel/administración & dosificación , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/tratamiento farmacológico , Adulto , Animales , Estudios de Cohortes , Femenino , Humanos , Masculino , Recuento de Huevos de Parásitos , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Esquistosomiasis mansoni/prevención & control , Esquistosomiasis mansoni/transmisión , Factores SocioeconómicosRESUMEN
The antischistosomal activity of clonazepam, when administered alone or in association with oxamniquine and praziquantel, was experimentally evaluated in mice infected with Schistosoma mansoni. The animals were treated 45 days post-infection with a single dose, by oral route, according to three treatment schedules: clonazepam 25 mg/kg and sacrificed 15 min, 1h or 4 h after treatment; clonazepam 1.0, 2.5 or 10.0 mg/kg and sacrificed 15 days post-treatment or with the dose of 10 mg/kg in association with oxamniquine 50 mg/kg or praziquantel 200 mg/kg, single dose, orally, every schedule with a control group. The efficacy of the drugs in vivo was assessed by means of worm counts and their distribution in mesentery and liver, mortality and oogram changes. In the chemotherapeutic schedules used, clonazepam did not present antischistosomal activity and the result of the association of this drug with oxamniquine or praziquantel was not significantly different from the one obtained when these two last drugs were administered alone. In the in vitro experiments, the worms exposed to 0.6 mg/mL clonazepam remained motionless throughout the 8-day-period of observation, without egg-laying, whereas the worms of the control group showed normal movements, egg-laying and hatching of miracidia on the last day of observation. The results obtained in the present study confirm the action of clonazepam on S. mansoni adult worm, in vitro, causing total paralysis of males and females. However, no additive or synergistic effects were observed when clonazepam were used in association with oxamniquine or praziquantel.
Asunto(s)
Clonazepam/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/farmacología , Animales , Clonazepam/administración & dosificación , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Femenino , Hígado/parasitología , Masculino , Mesenterio/parasitología , Ratones , Oxamniquina/administración & dosificación , Oxamniquina/farmacología , Praziquantel/administración & dosificación , Praziquantel/farmacología , Esquistosomicidas/administración & dosificación , Factores de TiempoRESUMEN
The activity of lovastatin associated with oxamniquine or praziquantel against schistosomiasis mansoni was evaluated in mice infected with Schistosoma mansoni. Forty days after infection, mice were treated with lovastatin, 400 mg/kg for five consecutive days by oral route, and on the last day of this sequence with 50 mg/kg oxamniquine or with 200 mg/kg praziquantel, both by oral route, single dose. Fifteen days later, the animals were perfused in parallel with an untreated control group. Studies were carried out in vitro, using lovastatin in culture medium containing S. mansoni worms proceeding from experimentally infected mice. In the in vivo trials, the association of lovastatin with oxamniquine or praziquantel did not show any additive action, but there were oogram changes when lovastatin was associated with oxamniquine. In vitro lovastatin was able to interrupt the maturation of S. mansoni eggs, which remained at the 1st or 2nd stages, depending on the dose used. The total number of morphologically dead eggs found in culture of worms exposed to 2 microg/ml or 4 microg/ml concentrations of lovastatin was significantly higher than the number of viable eggs. Using the probe Hoescht 33258 it was observed that 70% of the eggs considered morphologically viable in the treated groups (against 16% in the control group) were labeled, indicating that the majority of the viable eggs had membrane permeability increased due to lovastatin action.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lovastatina/uso terapéutico , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéutico , Animales , Quimioterapia Combinada , Ratones , Oxamniquina/uso terapéutico , Praziquantel/uso terapéutico , Schistosoma mansoni/enzimologíaRESUMEN
Schistosomiasis is still a public health problem in Brazil. The Kato-Katz test is the most frequently used diagnostic method for Schistosoma mansoni infection. However, it lacks sensitivity in areas of low prevalence. We have assessed the positivity rate of S. mansoni infection in Bananeiras, a village on Capistrano, Ceara, Brazil by performing a point-of-care test in urine to determine the circulating cathodic antigens (POC-CCA), and we compared the findings with those of the Kato-Katz technique for egg detection in stool and an enzyme-linked immunosorbent assay for specific antibodies against adult worms (SWAP-ELISA) in serum before treatment (baseline). Additionally, the POC-CCA and Kato-Katz test results were compared at one and two years post-treatment, and only POC-CCA strips were utilised for follow-up testing on urine samples at 3-6 weeks. Only one sample of stool and urine was collected per event. Overall, 258 individuals were investigated at the baseline. The POC-CCA test detected 10 (3.9%) positive cases; however, this amount increased to 30 (11.6%) when considering trace readings as positive (tâ¯+â¯), whereas the Kato-Katz method found only 4 (1.6%) positive cases and the SWAP-ELISA detected 105 (40.7%) positive cases. The consistency observed between a single POC-CCA (tâ¯+â¯) or (t-) and the Kato-Katz (three slides) was poor (Kappa indexes <0.20). The highest positivity rate as determined by CCA and Kato-Katz was found in adults. At the baseline, a praziquantel treatment was administered to all individuals regardless of their infection status. According to the POC-CCA test, 93% of the previous positive cases became negative by the third week after the treatment; this rate reached 100% at the sixth week assessment. The follow-up showed that of the 175 individuals evaluated at one year post-treatment, only one (0.6%) showed 'trace' results, and all the individuals were negative for eggs in the stool. At two years, all 185 examined individuals were negative by the Kato-Katz method, and 11 (5.9%) presented traces by POC-CCA. Our results indicate that a single POC-CCA test reveals a significantly higher number of positive cases than the Kato-Katz technique for diagnosing S. mansoni in a low endemic setting, when trace results are considered as positive cases. Nevertheless, the true significance of the trace is not clear. These findings reinforce the need to associate different tools for improved schistosomiasis diagnosis in individuals with low parasite burdens.
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Anticuerpos Antihelmínticos/análisis , Antígenos Helmínticos/análisis , Sistemas de Atención de Punto , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/diagnóstico , Pruebas Serológicas/métodos , Adulto , Animales , Antihelmínticos/uso terapéutico , Brasil , Niño , Ensayo de Inmunoadsorción Enzimática , Heces/parasitología , Femenino , Humanos , Masculino , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Sensibilidad y EspecificidadRESUMEN
Background: Prior to eliminating schistosomiasis, efforts must address accurate and fast individual diagnosis. Diagnosis is still inaccurate by parasitological and point-of-care circulating cathodic antigen (POC-CCA) in areas of low endemicity. Methods: Our group has optimized POC-CCA with a 30 min urine concentration step with no need for specialized technicians or equipment and with high accuracy. We evaluated this new method, called POC-CCA filter (FLT), in two Brazilian endemic areas with distinct profiles. Results: At baseline, POC-CCA had a poor performance with several false results and undefined trace readings, revealing a prevalence rate of 10% against a rate of 23% for POC-CCA FLT, which was similar to the parasitological rates. Accuracy increased from as low as 0.36 to 0.96 after urine concentration in one area. POC-CCA properly diagnosed only half of the cases at three post-treatment time points, while POC-CCA FLT was able to diagnose 96, 83 and 100%, respectively. Conclusions: The improvement of conventional POC methodology by a fast and simple urine concentration step provided not only an increase in its accuracy before and after praziquantel treatment, but also preserved its applicability in low-prevalence endemic areas, allowing the definition of trace readings as negative cases.
Asunto(s)
Antígenos Helmínticos/orina , Sistemas de Atención de Punto , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/orina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antihelmínticos/uso terapéutico , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Praziquantel/uso terapéutico , Estudios Prospectivos , Reproducibilidad de los Resultados , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/epidemiología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
ABSTRACT Background: The World Health Organization recommends a market-ready, urine-based point-of-care diagnostic test for circulating cathodic antigens (CCA) to determine the prevalence of S. mansoni. This study evaluated the performance of the URINE CCA (SCHISTO) ECO TESTE® (POC-ECO), which is currently available in Brazil. Methods: Residents from eight sites with different prevalence estimates provided one urine sample for POC-ECO and one stool sample for Kato-Katz (KK) and Helmintex® (HTX) testing as an egg-detecting reference for infection status. Results: None of the study sites had significantly higher POC-ECO accuracy than KK. Conclusions: POC-ECO is not currently recommended in Brazilian schistosomiasis elimination programs.
RESUMEN
The impact of ivermectin on adult snails of the genus Biomphalaria (B. glabrata, B. tenagophila and B. straminea), B. glabrata infected with Schistosoma mansoni, snail egg-masses cercariae and miracidia, as well as on guppy fish (Poecilia reticulata) was examined and evaluated. Biomphalaria snails, egg-masses, parasite stages and guppies were all exposed to different concentrations of ivermectin for 24 h, followed by regular observations of mortality. The calculated lethal doses of ivermectin were around an LD50 of 0.03 µg ml-1, and an LD90 of 0.3 µg ml-1 for the three species of snails. Specimens of B. glabrata actually shedding parasite cercariae all died when exposed to ivermectin at a concentration of a mere 0.01 µg ml-1. Ivermectin B1a, the major (80%) component of commercially available ivermectin, proved to be inactive, and it was the minor (20%) component, ivermectin B1b, which caused snail death. Snail egg-masses were not affected, even at the highest concentration of 100 µg ml-1. With respect to S. mansoni parasite stages, 0.2 µg ml-1 ivermectin killed 50% of cercariae and miracidia within five minutes, rising to 90% after 30 min. Mortality of guppy fish within 24 h of exposure to ivermectin at concentrations of 0.5 µg ml-1 and 0.01 µg ml-1, were 100% and 30%, respectively. The concentration of 0.01 µg ml-1 that killed Schistosoma mansoni-infected snails only caused 30% mortality in guppy fish. Ivermectin can be considered a promising molluscicide, especially as it is more potent against infected snails than uninfected ones, although it has no impact on egg-masses. Ivermectin and its derivatives could be explored in the search for a new agent to help control schistosomiasis transmission.