"Oxamniquine"

Large CRISPR-Cas-induced deletions in the oxamniquine resistance locus of the human parasite Schistosoma mansoni. At least 250 million people worldwide suffer from schistosomiasis, caused by worms. Genome sequences for several species are available, including a high-quality annotated reference for . There is a pressing need to develop a reliable functional toolkit to translate these data into new biological insights and targets for intervention. CRISPR-Cas9 was recently demonstrated for the first time in , to produce somatic mutations in the ( ) gene. We employed CRISPR-Cas9 to introduce somatic mutations in a second gene, , a sulfotransferase expressed in the parasitic stages of , in which mutations confer resistance to the drug oxamniquine. A 262-bp PCR product spanning

Assessment of tegumental damage to Schistosoma mansoni and S. haematobium after in vitro exposure to ferrocenyl, ruthenocenyl and benzyl derivatives of oxamniquine using scanning electron microscopy Schistosomiasis is one of the most harmful parasitic diseases worldwide, praziquantel being the only drug in widespread use to treat it. We recently demonstrated that ferrocenyl, ruthenocenyl and benzyl derivatives of oxamniquine (Fc-OXA, Rc-OXA and Bn-OXA) are promising antischistosomal drug candidates. In this study we assessed the tegumental damage of these three derivatives of oxamniquine using scanning electron microscopy. Adult Schistosoma mansoni and S. haematobium were exposed to a concentration of 100 μM of each drug and incubated for 4-120 h, according to their onset of action

Immunohistochemical investigations of treatment with Ro 13-3978, praziquantel, oxamniquine and mefloquine in Schistosoma mansoni-infected mice. To date, there is only one drug in use, praziquantel, to treat more than 250 million people afflicted with schistosomiasis, a debilitating parasitic disease. The aryl hydantoin Ro 13-3978 is a promising drug candidate with activity superior dissected before and after the drug's onset of action. The veins and livers were excised, paraffin-embedded, and sectioned, and macrophages (IBA-1), neutrophils (Neutro), B cells (CD45R), and T cells (CD3) were stained by immunohistochemistry. For comparison, samples from infected untreated mice and mice treated with effective doses of praziquantel (400 mg/kg), oxamniquine (200 mg/kg), and mefloquine

Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population Molecular surveillance provides a powerful approach to monitoring the resistance status of parasite populations in the field and for understanding resistance evolution. Oxamniquine was used to treat Brazilian schistosomiasis patients (mid-1970s to mid-2000s) and several cases . We sequenced SmSULT-OR from 189 individual miracidia (1-11 per patient) recovered from 49 patients, and tested proteins expressed from putative resistance alleles for their ability to activate oxamniquine. We found nine mutations (four non-synonymous single nucleotide polymorphisms, three non-coding single nucleotide polymorphisms and two indels). Both mutations (p.E142del and p.C35R) identified

Orange Drugs: Idarubicin, Ferrioxamine, Oxamniquine, Phenazopyridine, Rifampicin, Sulfasalazine, Warfarin Food

no effect on eggs or immature worms. Follow-up at 4-6 weeks is recommended with repeat of treatment in 6-12 weeks.[10]Oxamniquine is the only alternative; it is used in intestinal infections in Africa and South America, where praziquantel is less effective. The use of oxamniquine is declining but is effective.[12]Metrifonate, which was effective for urinary infections, has been withdrawn from

in the abdominal lesion and in a rectal biopsy specimen. Ultrasonography revealed hepatic involvement. Despite combination treatment with oxamniquine and praziquantel, a cutaneous lesion persisted on the left elbow; a new biopsy revealed amastigote forms of Leishmania. The patient was successfully treated with intramuscular and intralesional meglumine antimoniate. The presence of a similar granulomatous

splenomegaly and leukopenia (p=0.046); however, only 4.5% of the patients had esophageal hemorrhage. Some patients received a specific treatment; of those, 42% took praziquantel, and 35.4% took oxamniquine. Nonspecific drug therapy was given as follows: 65% received propranolol, 90% omeprazole, and 43.6% aluminum hydroxide. The other treatments were as follows: 92.9% of patients underwent endoscopic

. With the exception of a few drugs, such as oxamniquine and metrifonate, most of the antischistosomals developed in the pre-praziquantel period have variable limitations with respect to safety and efficacy. Although oxamniquine and metrifonate have been used for schistosomiasis control, they are only effective against Schistosoma mansoni and S. haematobium, respectively. Currently, praziquantel is the only drug

Structural and enzymatic insights into species-specific resistance to schistosome parasite drug therapy The antischistosomal prodrug oxamniquine is activated by a sulfotransferase (SULT) in the parasitic flatworm Of the three main human schistosome species, only is sensitive to oxamniquine therapy despite the presence of SULT orthologs in and The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of and SULTs, including SULT in complex with oxamniquine. We also examined the activity of the three enzymes ; surprisingly, all three are active toward oxamniquine, yet we observed differences in catalytic efficiency that implicate kinetics as the determinant for species-specific toxicity. These results provide guidance

In-silico screening of Schistosoma mansoni Sirtuin1 inhibitors for prioritization of drug candidates Schistosomiasis is a common, neglected parasitic disease caused by Schistosoma mansoni. Availability of two specific drug oxamniquine and praziquintel for treatment of the disease is a major concern. Recently NAD+ dependent lysine deacetylases have been identified as new drug targets in pathogens

ConsiderationsPraziquantel is currently the main antischistosomal agent. Other oral agents are oxamniquine and metrifonate, but these have limited parasite specificity. Artemether appears to be beneficial in some settings.Surgery may be necessary in severe or chronic schistosomiasis. Patients who have chronic liver disease or are experiencing further episodes of gastrointestinal (GI) bleeding or bacterial sepsis should

/microliter). Phase contrast microscopy revealed intact erythrocytes, suggestive of postrenal hemorrhage. Proteinuria, erythrocyturia, and leukocyturia correlated significantly with the ova excretion in the urine, but not with egg excretion in the stool. Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings. In patients treated effectively with Praziquantel

, the other (II) was treated with a single oral doses (100 mg/kg) of oxamniquine at the 13th week. After treatment infections were maintained bi-weekly. Mortality was significantly higher in group I (p less than 0.0001). A comparative morphological and immunoenzymatic study of the liver in the two groups was also carried out, showing a tendency to smaller granulomas and to more efficient antigen restriction

, which were treated with metrifonate (two doses of 10 mg/kg bodyweight), oxamniquine (60 mg/kg), praziquantel (40 mg/kg), or a multivitamin preparation, respectively. Serum, stool and urine samples were taken prior to treatment as well as one month and five months after chemotherapy. Before chemotherapy CAA levels were similar in the four groups. Antigenemia remained unchanged in the control group . In patients treated with praziquantel or oxamniquine the concentration of CAA decreased to a similar extent. However, whereas in the praziquantel group absence of CAA was already observed one month after treatment, clearing of CAA from the circulation seemed to take longer in patients treated with oxamniquine. Treatment with metrifonate did not result in a reduction of the CAA titres.

The effect of metrifonate in mixed Schistosoma haematobium and Schistosoma mansoni infections in humans. In order to examine the effect of metrifonate, 156 patients with mixed Schistosoma haematobium and mansoni infection were randomly divided into three groups and treated with metrifonate (twice 10 mg/kg body weight), oxamniquine (60 mg/kg) and praziquantel (40 mg/kg), respectively. The output of S. haematobium and S. mansoni ova were quantitatively assessed in urine and stool. Application of metrifonate resulted in a similar reduction of S. haematobium and S. mansoni eggs in the urine, whereas no effect on egg excretion was observed in the stool irrespective of the parasite species. In contrast, oxamniquine influenced the output of S. mansoni ova in stool and urine, but showed no effect

A prospective, randomized therapeutic trial for schistosomal specific nephropathy. In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs

Field study of different oxamniquine dose for Schistosoma mansoni in Gezira, Sudan. Two hundred and ninety-six individuals of whom 126 were children and 170 adults with positive stool for Schistosoma mansoni were randomly given oxamniquine treatment in a dose of either 20, 40 or 60 mg/kg body wt. They were followed in the field for ova excretion at 1, 3 and 6 months for adults and at 1, 3, 6 and 8 months for children. The cure rates in adults at 6 months are 93%, 87% and 73% for the 60, 40, 20 mg/kg-1 treatments in order. For children the cure rates at 6 months are 36%, 58% and 63% and at 8 months are 16%, 21% and 26% for corresponding doses. There is no difference in egg reduction for those not cured between the three treatments at 6 months. It is concluded that oxamniquine need

Treatment of patients with schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine.

Two-year follow-up of Schistosoma mansoni infection and morbidity after treatment with different regimens of oxamniquine and praziquantel. Three study groups in the Rusizi plain (Burundi) were examined parasitologically (duplicate 28 mg Kato slides) and clinically (history, abdominal palpation) 0, 1.5, 3, 6, 12 and 24 months after treatment for Schistosoma mansoni infection. Infected subjects in Maramvya (n = 430) were treated randomly with oxamniquine 20, 30 or 40 mg/kg; those in Bulinga (n = 457) with praziquantel, 20, 30 or 40 mg/kg; those in Bulamata (n = 333) with praziquantel, 30 or 40 mg/kg. In children (less than 20 years) in Maramvya and Bulamata, infection rates and intensities returned almost to pretreatment levels one to 2 years after treatment. In Bulinga, reinfection in children