Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. METHODS: Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF ß1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. RESULTS: A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-ß1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). CONCLUSION: Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Rutin, a Flavonoid Compound Derived from Garlic, as a Potential Immunomodulatory and Anti-Inflammatory Agent against Murine Schistosomiasis mansoni.

Schistosomiasis is a tropical disease caused by trematode worms. The inflammatory response of the host to schistosome eggs leads to formation of granuloma in the liver and intestine. Praziquantel (PZQ) is still an effective treatment for schistosomiasis, however resistance development may reduce its efficacy. The current study investigated the possible immunomodulatory and anti-inflammatory action of rutin, a natural flavonoid compound isolated from garlic, on liver fibrotic markers in mice infected with S. mansoni in comparison to PZQ. Male albino CD1 mice were infected with 100 ± 2 S. mansoni cercariae/mouse and treated with garlic, rutin, or PZQ. At the end of the experiment, the liver and intestines were harvested for parasitological and histological assessment and to analyze the proinflammatory cytokine. Rutin significantly affects the pathological alterations caused by Schistosoma in the liver. This may be partially explained by a decrease in the number of eggs trapped in the tissues of the liver and a modification in the serum levels of certain cytokines, which are implicated in the formation of Schistosoma granuloma. In conclusion, rutin has strong anti-schistosome properties in vivo, raising the possibility that rutin might be further investigated as a therapy for S. mansoni.

Bioactivity of Trigonella foenum (Fenugreek) oil on immunological and biochemical response of Schistosoma mansoni infected mice.

The effect of fenugreek oil (FO) on some parasitological, immunological, and biochemical parameters in mice infected with Schistosoma mansoni were investigated. Chromatography mass spectrometry (GC/MS) analysis of FO revealed that linoleic acid, (E,E)-4-decadienal, and isopropyl myristate are the major constituents of FO. The results showed that treatment of S. mansoni-infected mice with 0.15 ml of FO daily for 10 successive days exhibited a significant reduction in the number of S. mansoni male worms, and coupled worms as compared to an infected control group (p < 0.05). Regarding total egg counts and oogram patterns, FO effectively reduced the percentage of hepatic and intestinal egg counts, and elevated immature and dead eggs in ratios closely to praziquantel (PZQ) treated mice. Meanwhile, FO significantly elevated the levels of glutathione and co-enzyme Q-10 (COQ-10) up to 0.33±0.02 ng/ml and 0.28±0.02 ng/ml, respectively. However, when accompanied with PZQ, COQ-10 level was closer to that of the normal control group (0.37 ± 0.021 ng/ml). The result also showed that FO significantly reduced levels of lipid per-oxidation (0.165±0.01 ng/ml) and vascular endothelial growth factor (0.25±0.02 pg/ml) as compared to the PZQ-treated group (0.234±0.02 ng/ml and 0.31±0.008 pg/ml, respectively). Moreover, FO recovered normal values of caspase-7, and when accompanied with PZQ, annexin-V was also significantly reduced. However, treatment of S. mansoni-infected mice with PZQ led to a significant increase in the level of annexin-V as compared to S. mansoni-infected mice group (p < 0.05). It can be concluded that FO may have a potential anti-schistosomal, antioxidant and anti-inflammatory activities. Also, it may have a recovering effect on apoptotic parameters toward the normal values.

In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice.

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

[Implementation of a network drug strategy: the case of praziquantel]. / Implementación de una estrategia de medicamentos en red: el caso de praziquantel.

Parasitic infections cause a huge burden of disease and are a current public health problem. The category of emerging or re-emerging disease is influenced by phenomena that occur in today's interconnected world because of globalization, the displacement of people, trade, uncoordinated urbanization and climate change, they have a very important influence on transmission of these diseases. In 2021 there was an increase in the number of patients who have required treatment for diphyllobothriasis in the Los Ríos Region. This article reviews aspects related to integrated Health Service networks to provide access to pharmacological treatments to patients diagnosed with diphyllobothriasis (tapeworm infection), implemented by the Valdivia Health Service Department, in collaboration with the San José de Osorno hospital, primary care centers and private centers in the Los Ríos Region.

Schistosomicidal and hepatoprotective activity of gamma-aminobutyric acid (GABA) alone or combined with praziquantel against Schistosoma mansoni infection in murine model.

OBJECTIVE: This study aimed to evaluate the efficacy of gamma-aminobutyric acid (GABA) alone or combined with praziquantel (PZQ) against Schistosoma (S) mansoni infection in a murine model. METHODS: Five groups, 8 mice each, were studied; GI served as normal controls; GII: S. mansoni-infected control group and the other three S. mansoni-infected groups received drug regimens for 5 consecutive days as follows GIII: Infected-PZQ treated group (200 mg/kg/day); GIV: Infected-GABA treated group (300 mg/kg/day) and GV: Infected-PZQ-GABA treated group (100 mg/kg/day for each drug). All animal groups were sacrificed two weeks later and different parasitological, histopathological and biochemical parameters were assessed. RESULTS: Combined GABA-PZQ treated group recorded the highest significant reduction in all parasitological, histopathological and biochemical parameters followed by PZQ and finally GABA groups. Combined GABA-PZQ treatment led to the complete disappearance of immature eggs and marked reduction of deposited eggs in liver tissues and improved liver pathology. Significant improvement in hepatic oxidative stress levels, serum albumin and total protein in response to GABA treatment alone or combined with PZQ. CONCLUSION: GABA had schistosomicidal, hepatoprotective and antioxidant activities against S. mansoni infection, GABA disrupted parasite pairing and activity, reduced the total number of worms recovered and the number of ova in the tissues. GABA may be considered an adjuvant therapy to potentiate PZQ antiparasitic activity and eradicate infection-induced liver damage and oxidative stress.

Implementación de una estrategia de medicamentos en red: el caso de praziquantel / Implementation of a network drug strategy: the case of praziquantel

Resumen Las infecciones parasitarias provocan una enorme carga de enfermedad y constituyen un problema presente para la salud pública. Las enfermedades emergentes o reemergentes se ven influenciadas por fenómenos del mundo actual interconectado producto de la globalización, el desplazamiento de las personas, el comercio, la urbanización descoordinada y el cambio climático, contribuyendo en la transmisión de estas enfermedades. En el año 2021 hubo un aumento de la cantidad de pacientes que han requerido tratamiento para la difilobotriasis en la Región de los Ríos. Se revisan los aspectos relacionados con las redes integradas de servicios de salud para el acceso al tratamiento farmacológico a pacientes con diagnóstico de difilobotriasis, implementado por la Dirección de Servicio de Salud Valdivia, en colaboración con el hospital San José de Osorno, centros de atención primaria y centros privados de la Región de los Ríos.

Abstract Parasitic infections cause a huge burden of disease and are a current public health problem. The category of emerging or re-emerging disease is influenced by phenomena that occur in today's interconnected world because of globalization, the displacement of people, trade, uncoordinated urbanization and climate change, they have a very important influence on transmission of these diseases. In 2021 there was an increase in the number of patients who have required treatment for diphyllobothriasis in the Los Ríos Region. This article reviews aspects related to integrated Health Service networks to provide access to pharmacological treatments to patients diagnosed with diphyllobothriasis (tapeworm infection), implemented by the Valdivia Health Service Department, in collaboration with the San José de Osorno hospital, primary care centers and private centers in the Los Ríos Region.

Evaluation of Antischistosomal Activities of Crude Aqueous Extracts of Artemisia annua, Nigella sativa, and Allium sativum against Schistosoma mansoni in Hamsters.

Schistosomiasis is a neglected disease, as the World Health Organization classified it in the second category after malaria. World Health Organization approved praziquantel (PZQ) as the only chemotherapy to treat schistosomiasis. Over the years, some problems have arisen with PZQ, as it showed poor efficacy in the early stages of infection as well as the emergence of some resistance to it. In searching for new alternative drugs to treat schistosomiasis, the researchers intensified their efforts to find a new drug. The present study focuses on evaluating the effect of three plant extracts Artemisia annua, Nigella sativa, and Allium sativum at different doses of 31.25, 62.5, 125, 250, and, 500 µg/ml; in vitro study was accomplished on the Schistosoma mansoni adult worms. The results declared that the concentration of 500, 250, and 125 of Artemisia annua was more effective on adult worms, and the same concentrations of Nigella sativa and Allium sativum gave less effect on the adult worms than the previous plant. In vivo study was accomplished on the hamster's tissue after exposing it to doses of the plants' extracts with different concentrations; it showed the presence of calcifications and damage to the worm eggs in the liver and spleen, as well as reducing the size of granulomas. After conducting many confirmatory studies Artemisia annua extract can be used as an effective and safe treatment for Schistosoma disease.

Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community.

BACKGROUND: Evidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1. This community-based intervention study was conducted to assess whether ShTAL1IgE responses post-treatment with praziquantel (PZQ) might be associated with a reduced risk to re-infection with S. haematobium. METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted at Agona Abodom, Central Region, Ghana, and involved 114 participants aged 6 to 55 years. EDTA blood samples were collected at baseline and 7 weeks after PZQ treatment (Follow-up). Baseline and Follow-up titres of specific IgG1, IgG4, and IgE antibodies to the S. haematobium-specific adult worm antigen (ShAWA), the Sh-specific soluble egg antigen (ShSEA), and the Sh-specific tegumental-allergen-like 1 protein (ShTAL1) in plasma samples were measured using sandwich ELISA. Participants at both time points also provided stool and urine for helminth egg detection by microscopy. Prevalence of S. haematobium at baseline was 22.80%, and decreased to 3.50% at Follow-up. The egg reduction rate (ERR) was 99.87%. Overall plasma levels of ShTAL1-IgE increased 7 weeks post-PZQ treatment, and with increasing age; whiles S. haematobium infection prevalence and intensity decreased. For S. haematobium-infected participants who were egg-negative at Follow-up (N = 23), minimal median levels of ShTAL1-IgE were observed for all age groups prior to treatment, whilst median levels increased considerably among participants aged 12 years and older at Follow-up; and remained minimal among participants aged 11 years or less. In the univariate analysis, being aged 12 years or older implied an increased likelihood for ShTAL1-IgE positivity [12-14 years (cOR = 9.64, 95% CI = 2.09-44.51; p = 0.004); 15+ years (cOR = 14.26, 95% CI = 3.10-65.51; p = 0.001)], and this remained significant after adjusting for confounders [12-14 years (aOR = 22.34, 95% CI = 2.77-180.14; p = 0.004); ≥15 years (aOR = 51.82, 95% CI = 6.44-417.17; p < 0.001)]. Conversely, median ShTAL1-IgG4 titres were hardly detectible at Follow-up. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that increased IgE levels to ShTAL1 7 weeks after PZQ treatment could be associated with a reduced risk to re-infection, and adds to the large body of evidence suggesting a protective role of the treatment-induced ShTAL1 antigen in schistosomiasis infections. It was also quite clear from this work that apart from being persistently S. haematobium-positive, elevated ShTAL1-IgG4 levels at Follow-up could be indicative of susceptibility to re-infection. These outcomes have important implications in vaccine development, and in shifting the paradigm in mass chemotherapy programmes from a 'one-size-fits-all' approach to more sub-group-/participant-specific strategies in endemic areas.

Potentiality of curcumin on ISHAK scoring system and the expressions of BAX, IL-17A, and EGF in the treatment ofSchistosoma mansoni infection using Swiss albino mice.

The present study evaluated the antiparasitic effect of curcumin extract on Schistosoma mansoni in Swiss albino mice. The experimental design included four groups of S. mansoni - infected mice; without treatment (controls), curcumin-treated, Praziquantel (PZQ)-treated, and PZQ +curcumin treated mice. The results showed that curcumin improved ISHAK confluent necrosis score up to zero. PZQ +curcumin showed a significant reduction in portal inflammation. Both activity and fibrosis demonstrated lower scores in all treated groups, however, PZQ revealed a marked increase in confluent necrosis and interface hepatitis. Besides, the lobular inflammation revealed worsening in the overall ISHAK score in all treated groups compared with the control. Few periocular granulomas were recovered by PZQ +curcumin treatment at day 35 post-treatment (6±1.2), P-value <0.05. Curcumin revealed a mild reduction (60±7.376). Curcumin-treated groups, with and without PZQ, resulted in higher significant Immunoreactivity score (IRS) for Bcl-2-associated X (BAX) and lower Interleukine- 17A (IL-17A), and Human epidermal growth factor (EGF), compared to the control. However, PZQ revealed a lower mean IRS value in BAX, higher IL-17A and EGF in the periovulatory granuloma. It was concluded that PZQ +curcumin treatment had a potent synergistic outcome through lessening the number of granulomas, the inflammatory events, and the expression of EGF, and amelioration of apoptosis in the periovulatory granulomas if compared with either PZQ or curcumin alone.

Dandelion (Taraxacum officinale) Improves the Therapeutic Efficiency of Praziquantel in Experimental Schistosomiasis.

PURPOSE: Although praziquantel (PZQ) has a wide use as an anti-schistosome agent, many of its imperfections and side effects have been reported in many studies. The current study aims to evaluate the curative effect of a natural dandelion extract (Taraxacum officinale) on schistosomiasis either alone or in combination with PZQ based on parasitological, immunological, histopathological and molecular investigations. METHODS: Mice were experimentally infected with Schistosoma mansoni cercariae and then divided into four groups, Schistosoma spp.-infected untreated group (IC group), Schistosoma spp.-infected group of mice treated with dandelion (I-Dn group), Schistosoma spp.-infected group of mice treated with PZQ (I-PZQ group), and Schistosoma spp.-infected group of mice treated with both PZQ and dandelion (I-PZQ + Dn group). Treatment started 45 days' post-infection. Besides, non-infected, non-treated mice served as the negative healthy control group (HC group). RESULTS: The present results indicated that dandelion administration significantly reduced the worm burden, ova number, and the number and diameter of hepatic granulomas as compared to the untreated infected group. The results also showed that the levels of IL-6 and TNF-α were significantly decreased in the combined treatment group (I-PZQ + Dn) as compared to the I-PZQ group. Administration of dandelion-only remarkably reduced AST and ALT activities associated with schistosomiasis. Moreover, hepatic DNA damage assessed by comet assay was significantly inhibited in the combined treated group compared to the infected untreated and PZQ treated groups. CONCLUSION: The results concluded that combined treatment of PZQ and dandelion extract improved immune response, decreased the number and diameter of granulomas, and inhibited DNA damage, indicating a reduction in liver fibrosis associated with schistosomiasis. The present study focused on the potential effect of dandelion as an adjunct medication for therapeutic properties of PZQ.

Parasitological and Biochemical Efficacy of the Active Ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni Infected Mice.

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.

Efficacy of Mebendazole and Praziquantel against Soil-Transmitted Helminths and Schistosoma mansoni Infections among Schoolchildren in Northwest Ethiopia.

BACKGROUND: Soil-transmitted helminths (STHs) and Schistosoma mansoni are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited. OBJECTIVE: This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and Schistosoma mansoni parasites. METHODS: A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for Schistosoma mansoni with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and S. mansoni parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel. RESULTS: Among 422 participants, the prevalence of STHs, hookworm, Ascaris lumbricoides, and S. mansoni was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against A. lumbricoides increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against S. mansoni-infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs. CONCLUSION: The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and A. lumbricoides are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat S. mansoni. Therefore, single-dose praziquantel to S. mansoni and redosing of single-dose mebendazole to A. lumbricoides and hookworm infections can be used for treatment purposes.

Validation of a human-serum-based in vitro growth method for drug screening on juvenile development stages of Schistosoma mansoni.

BACKGROUND: Schistosomiasis affects over 200 million people worldwide but only praziquantel is available for treatment and control. Drug discovery is often based on phenotypic drug screening, involving different parasite stages retrieved from infected mice. Aiming to reduce animal use, we validated an in vitro growth method for juvenile Schistosoma mansoni for the purpose of drug sensitivity assays. METHODOLOGY/PRINCIPAL FINDINGS: We compared inter-batch variability of serum, worm size and organ development, gender distribution, and drug sensitivity between in vitro and in vivo grown worms over different life stages. In vitro developed S. mansoni in Hybridoma medium supplemented with 20% human serum were similar in size as in vivo worms until 28 days of incubation (males 1.4 ± 0.2 mm, females 1.1 ± 0.5 mm long). qPCR analysis revealed similar gender distribution both on newly transformed schistosomula and worms grown for 21 days. Worms developed in vitro and in vivo were similarly sensitive to praziquantel from 7 to 35 days of development with the exception of 21 days of development, where a slightly lower activity was observed for the in vitro grown worms (IC50: 0.54 µM in vitro, 0.14 µM in vivo 72 hours post-incubation). The evaluation of five additional drugs revealed a similar sensitivity on worms developed for 21 days, with the exception of mefloquine, where we observed a 10-fold lower sensitivity on in vitro developed schistosomes when compared to in vivo grown (IC50: 4.43 µM in vitro, 0.48 µM in vivo). CONCLUSION: A large number of juvenile S. mansoni worms can be grown in vitro, which show similar drug sensitivity, gender distribution, size and morphology as the worms recovered from rodents, supporting the use of this method in drug screening efforts.

Treatment of sarcoptic and chorioptic mange in an alpaca (Vicugna pacos) herd with a combination of topical amitraz and subcutaneous ivermectin.

Clinical history: An outbreak of intense pruritus and weight loss in a herd of 40 alpacas (Vicugna pacos) in the south-west of France was investigated after the death of 14 adults. One alpaca was referred to a veterinary teaching hospital for diagnosis and treatment but died soon after and one of the dead alpacas was submitted for necropsy. Clinical findings: The remaining alpacas were intensely pruritic with variably severe and extensive alopecia, erythema, lichenification and crusting on the face, ventral abdomen and distal limbs. Superficial skin scrapes from five animals revealed large numbers of Sarcoptes scabiei mites, and less frequent and numerous Chorioptes bovis mites. Coproscopic examinations revealed a median of 1,350 (min 500, max 8800) strongyle epg. The alpaca admitted for treatment was anaemic and hypoalbuminaemic. Skin scrapes revealed copious S. scabiei and C. bovis mites. The two alpacas examined post-mortem had similar skin lesions to those examined on-farm and were cachexic. One had lung lesions attributed to protostrongylid infestation and its liver contained numerous Dicrocoelium spp. adults. Diagnosis: Sarcoptic and chorioptic mange with secondary superficial bacterial skin infection, associated with severe internal parasitism and underfeeding. Treatment and outcome: All 25 alpacas were treated topically with a 3% chlorhexidine shampoo followed by a 0.025% amitraz wash at the initial visit and then 1, 2, 3, 7 and 9 weeks later. A systemic treatment with S/C 500 µg/kg ivermectin was administered at the initial visit and then 2, 7 and 9 weeks later. The alpacas were treated orally with 50 mg/kg praziquantel to control dicrocoeliosis. Nutritional measures, including increased pasture area and supplemental feeding were simultaneously implemented. Pruritus was reduced 1 week after the start of treatment and had resolved after 2 weeks. After 9 weeks, skin lesions were markedly improved. Six months after the initial visit, skin lesions entirely resolved and superficial skin scrapes, taken from half of the animals, were negative for mites. Clinical relevance: This is the first report of the use of two acaricides combined with a chlorhexidine shampoo to successfully treat simultaneous sarcoptic and chorioptic mange in alpacas.

Evaluation of prophylactic efficacy and safety of praziquantel-miltefosine nanocombination in experimental Schistosomiasis mansoni.

The control of schistosomiasis depends exclusively on praziquantel (PZQ) monotherapy with treatment failure due to minor activity against the juvenile stage, re-infection and emerging drug resistance. Improving the antischistosomal therapeutic/prophylactic profile of PZQ is a sensible option to save the clinical benefits of the drug if achieved effectively and safely via a single oral dose. Recently, we developed praziquantel-miltefosine lipid nanocapsules (PZQ 250 mg/kg-MFS 20 mg/kg LNCs) as a nanotechnology-enabled novel drug combination with significant multistage activity against Schistosoma mansoni (S. mansoni) in a murine model. The present study aimed at providing a proof of concept of the chemoprophylactic effect of this nanocombination. A single oral dose of the nanocombination was administered to mice one and seven days before challenge infection with S. mansoni. The protective effect of the nanocombination was assessed parasitologically and histopathologically relative to LNCs singly-loaded with PZQ or MFS and non-treated infected controls. In addition, the safety of the nanocombination was assessed biochemically and histopathologically. Administration of the nanocombination one or seven days pre-infection resulted in a statistically significant reduction in mean worm burden and granulomas size associated with amelioration of hepatic pathology compared to infected non-treated control. Although, the prophylactic effect was significantly reduced upon administration seven days pre-infection compared to administration one day pre-infection, yet, it still exists. Results were explained based on the spectrum of activity of PZQ and MFS and their complementary pharmacokinetic (PK) profiles in addition to the effect of nanoencapsulation on these factors. The novel PZQ-MFS nanocombination offers valuable potentials in PZQ-based mass drug administration programmes by granting radical cure, preventing re-infection, and delaying development of resistance to the component drugs.

Recurrent eosinophilic pleuritis caused by sparganum infection: A case report and review of the literature.

RATIONALE: Sparganosis is an infectious disease caused by a larval tapeworm of the genus Spirometra, which commonly invades subcutaneous tissues. Pulmonary and pleural involvement due to sparganum has been rarely reported previously. PATIENT CONCERNS: We herein described a case of recurrent eosinophilic pleuritis in a 24-year-old woman. She was admitted with persistent cough and shortness of breath for more than 1 month. Initial chest computed tomography scan suggested right pleural effusion and diffuse pleural thickening. Slightly elevated eosinophil counts were found in both the peripheral blood and pleural fluid. She underwent right pleurectomy but histological examination failed to obtain an etiological diagnosis. Moreover, eosinophilic pleural effusion re-appeared in the contralateral thoracic cavity one month later. After re-admission, we reviewed her medical history meticulously and found she had a history of ingesting raw snake gallbladders before hospitalization. The final diagnosis was confirmed by the markedly positive reaction against sparganum antigen in both serum and pleural fluid sample. DIAGNOSIS: Eosinophilic pleuritis caused by sparganum infection. INTERVENTIONS: After the diagnosis, the patient was treated with praziquantel at 75 mg/kg/d for 3 days. OUTCOMES: Pleural effusion absorbed completely and eosinophil count in peripheral blood returned to normal range. No evidence of recurrent pleural effusion had been observed in over one year of follow-up. LESSONS: Clinicians need to be aware the possibility of sparganum infection in cases of eosinophilic pleuritis. The specific enzyme-linked immunosorbent assay remains a useful method in acquiring a rapid diagnosis, especially when histological examination is unable to detect the larvae in the thoracic cavity.

Identification of transmission foci of Schistosoma mansoni: narrowing the intervention target from district to transmission focus in Ethiopia.

BACKGROUND: Schistosoma mansoni (S. mansoni) infection is a significant public health problem in Ethiopia, and has wide distribution in the country. The impact of the disease is particularly high on school-age children. Nationwide 385 endemic districts were identified, whereby control and elimination interventions are underway using school-based annual mass drug administration (MDA) with praziquantel. The national elimination program targets endemic districts as a whole. The aim of this study was to identify the transmission foci of Schistosoma mansoni and determine prevalence of soil-transmitted helminths (STHs) in Abeshge district. METHODS: The study was conducted from April to May, 2019 among school-age children randomly selected from public elementary schools in Abeshge district, South-central Ethiopia. Demographic information and data on risk factors of S. mansoni infection were gathered using pre-tested questionnaire. Moreover, a stool sample was collected from each child and examined using Kato-Katz thick smear technique. The data were analyzed using STATA_MP version 12. RESULTS: A total of 389 school-age children from five public elementary schools were included in the study. The overall prevalence of S. mansoni and STHs was 19.3% (75/389) and 35% (136/389), respectively. The prevalence of S. mansoni was 60.6% in Kulit Elementary school, while it was zero in Geraba. The prevalence of S. mansoni was significantly higher among males (AOR = 2.6, 95% CI 1.3-5.1), those with habit of swimming and/or bathing in rivers (AOR = 2.9, 95%CI 1.3-5.1) and involved in irrigation activities (AOR = 2.9, 95% CI 1.0-8.3). Overall, the prevalence of S. mansoni was significantly higher among school children attending Kulit Elementary School compared to those attending the remaining schools (AOR = 12.5, 95%CI 6.2-25.1). CONCLUSION: A wide variation of S. mansoni prevalence was observed among the school children in the different schools. Control interventions better identify and target foci of S. mansoni transmission, instead of targeting the district homogenously.

Schistosomiasis and soil-transmitted helminthiasis preventive chemotherapy: Adverse events in children from 2 to 15 years in Bengo province, Angola.

Preventive chemotherapy campaigns with praziquantel and albendazole are being implemented in Angola, as a high priority public health intervention. However, there are no published data regarding adverse events associated with these medications. In this context, we analysed adverse events due to co-administration of praziquantel and albendazole in endemic areas of schistosomiasis and soil-transmitted helminths in Bengo, Angola. In the context of a targeted drug administration, between December 2012 and September 2013, we conducted two surveys after co-administrating single oral doses of praziquantel and albendazole tablets to children 2 to 15 years of age. About 24 hours after each treatment, participants answered a questionnaire about adverse events. At baseline, 605 children (55.0% male; mean age: 9.7 years) were treated; 460 were interviewed and 257 (55.9%) reported at least one adverse event, 62.3% (160/257) of children being infected with schistosoma haematobium. After six months of treatment, among 339 children surveyed, 184 (54.3%) reported adverse events, with 49.5% (91/184) of infected children. Adverse events were most common in preschool-aged children, with no significant difference between genders. The most frequent adverse events in the two surveys were abdominal pain (18.5%, 25.7%), headache (20.9%, 23.0%) and dizziness (15.7%, 19.8%). Children aged 12 to 15 years (adjusted OR = 0.40, p = 0.040) and those with mixed infection (adjusted OR = 0.04, p = 0.011) had lower odds of adverse events. After the second treatment, those with heavy infection (adjusted OR = 2.72, p = 0.018) and aged 9-11 years (adjusted OR = 2.01, p = 0.049) had significantly fewer adverse events. About 2.0% of children experienced severe adverse events. This study adds evidence that preventive chemotherapy for schistosomiasis and soil-transmitted helminths control is safe, but cases of adverse events are expected. Standardized methodologies to discriminate drug-related adverse events from the clinical manifestations of the infections are needed.

Development and application of anthelminthic drugs in China.

China was once a country plagued by parasitic diseases. At the beginning of the founding of the People's Republic of China, nearly 80% of the population suffered from parasitic diseases because of poverty and poor sanitary conditions. After nearly 70 years of development, China has made remarkable achievements in the prevention and control of parasitic diseases, and the prevalence of parasitic diseases has been greatly reduced. In addition to organizational leadership from the government and various preventive measures, drug treatment and drug research & development are important and irreplaceable links in prevention and control work. Since the 1950s, China has begun to introduce, produce and imitate antiparasitic drugs from abroad, such as santonin, benzimidazole, and praziquantel. Chinese scientists have also contributed to the optimization of production techniques, improvements in drug formulation, the application in the clinic and the mechanisms of actions of generic drugs. At the same time, China has independently developed tribendimidine (TrBD, a broad spectrum anthelminthic), and its anthelminthic spectrum has been comprehensively studied. It is active against almost 20 parasites, is especially superior to benzimidazoles against Necator americanus, and surpasses the effectiveness of praziquantel against Clonorchis sinensis. In the treatment of tapeworm disease, the traditional Chinese medicines pumpkin seeds and betel nuts have good curative effects for taeniasis. Chinese scientists have explored the action modes and clinical administration methods of pumpkin seeds and betel nuts, which is still the main clinical regimen for the disease. This paper reviews the history and progress of the study of anthelmintics in intestinal helminth infections since the founding of the People's Republic of China and aiming to support clinicians and drug researchers in China and other countries.