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Abstract Background Drug resistance and toxic side effects are major challenges in the treatment of babesiosis. As such, new drugs are needed to combat the emergence of drug resistance in Babesia parasites and to develop alternative treatment strategies. A combination of naphthoquine (NQ) and artemisinin is an antimalarial therapy in pharmaceutical markets. The present study repurposed NQ as a drug for the treatment of babesiosis by evaluating the anti-Babesia activity of naphthoquine phosphate (NQP) alone. Methods An in vitro growth inhibition assay of NQP was tested on Babesia gibsoni cultures using a SYBR Green I-based fluorescence assay. In addition, the in vivo growth inhibitory effect of NQP was evaluated using BALB/c mice infected with Babesia rodhaini. The parasitemia level and hematocrit values were monitored to determine the therapeutic efficacy of NQP and the clinical improvements in NQP-treated mice. Results The half maximal inhibitory concentration of NQP against B. gibsoni in vitro was 3.3 ± 0.5 μM. Oral administration of NQP for 5 consecutive days at a dose of 40 mg/kg of body weight resulted in significant inhibition of B. rodhaini growth in mice as compared with that of the control group. All NQP-treated mice survived, whereas the mice in the control group died between days 6 and 9 post-infection. Conclusion This is the first study to evaluate the anti-Babesia activity of NQP in vitro and in vivo. Our findings suggest that NQP is a promising drug for treating Babesia infections, and drug repurposing may provide new treatment strategies for babesiosis. Graphical Abstract

The article offers information on the bioactivity of co-ArNp on Schistosoma haematobium and its snail vector Bulinus truncatus. It mentions Schistosoma haematobium infection is a major public health problem in most of Africa and the Middle East and praziquantel remains the only drug used for schistosomiasis control; and also mentions treatment of Schistosoma haematobium reduced worm motility.

Malaria and schistosomiasis are the two most important parasitic diseases in the tropics and sub-tropics with geographic overlap. Efforts have been made for developing new schistosomicidal drugs, or testing existing drugs originally used for non-related diseases. The antimalarial artemisinin–naphthoquine phosphate combination (CO-ArNp) was recently reported to be a promising novel antischistosomal therapy with potent in vivo activity against Schistosoma mansoni . In this work, we report the in vitro dose- and time-response effect of CO-ArNp against the Egyptian strain of S. mansoni , and its snail host, Biomphalaria alexandrina. Incubation of adult S . mansoni with CO-ArNp at 40 or 20 μg/ml for 48 or 72 h killed all worms. Exposure of S . mansoni miracidia and cercariae to the molluscicidal LC50 of CO-ArNp (16.8 μg/ml) resulted in 100% mortality of the free larval stages within 90 and 15 min, respectively. Moreover, incubation of adult B. alexandrina snails with this drug combination killed all snails at 40 μg/ml within 24 h. Scanning electron microscope revealed marked morphological and tegumental alterations on the different stages of the parasite and its snail soft tissue. Our study highlights the schistosomicidal and molluscicidal effects of artemisinin–naphthoquine phosphate. No doubt more studies are needed to clarify its potential value to control schistosomiasis. [ABSTRACT FROM AUTHOR]

Highlight: [•] Compound naphthoquine phosphate (CO-ArNp) was assessed as a novel antischistosomal drug. [•] Single oral dose of CO-ArNp in mice harbouring juvenile Schistosoma mansoni significantly reduced worm burdens. [•] CO-ArNp dose of 600mg/kg in mice harbouring 3week old S. mansoni killed all female worms. [•] CO-ArNp at 600mg/kg in mice harbouring adult S. mansoni significantly reduced worms and egg burdens. [•] CO-ArNp has promising schistosomicidal and ovicidal effects and improved hepatic lesions. [Copyright &y& Elsevier]

The compound naphthoquine phosphate is a novel antimalaria drug tablet containing a fixed-dose combination of naphthoquine phosphate and artemisinin in a 1:2.5 ratio. A randomized, open study on the safety and tolerability was conducted in 28 healthy male volunteers using a single oral dose of 350 mg, 700 mg, 1400 mg, or 2100 mg of artemisinin-naphthoquine phosphate. Pharmacokinetics at the last 3 doses were examined in 30 volunteers. Food effects were also determined. Serial blood samples up to 216 hours after single oral dose administration were analyzed for plasma concentrations using a validated high-performance liquid chromatography—tandem mass spectrometry assay. The compound was well tolerated at single doses up to 2100 mg. Increased exposure to naphthoquine phosphate and artemisinin was less than dose proportional and linear. The half-life of naphthoquine phosphate was approximately 255 hours. The combination increased the AUC0-t and Cmax of both artemisinin (by 71% and 49%) and naphthoquine phosphate (by 135% and 104%) compared with mono-therapy. Food intake greatly increased the AUC0-t of artemisinin with a ratio of 77% and reduced that of naphthoquine phosphate from 955 ± 352 μg·h/L under the fasted state to 446 ± 231 μg·h/L in the fed condition. The pharmacokinetics and safety profile of the drug support its continued investigation in future clinical studies. [ABSTRACT FROM PUBLISHER]

Abstract: All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400mg of naphthoquine+1000mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2±8.6h and 34.6±14.3h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1–99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment. [Copyright &y& Elsevier]

Naphthoquine phosphate and artemisinine are two antimalarials developed in China. Both drugs have proven to be efficacious and well tolerated as monotherapy as well as in combination in patients suffering from malaria. The Co-naphthoquine, a novel antimalarial combination, is an oral fixed combination tablet of the naphthoquine phosphate and artemisinine. Artemisinin is characterised by a rapid onset of schizonticidal action and a short half-life. Parasite clearance is, however, often incomplete when it is employed as a single agent unless high dosages are used over several days, but such a regimen may reduce patient compliance and increase the danger of toxicity. Naphthoquine phosphate, by contrast, has a slower onset of action and a longer half-life, associated with a low recrudescence rate. The two components act synergistically in animal, and clinically provide more rapid relief of symptoms and a higher cure rate than either component alone. The combination tablet was initially developed by the Academy of Military Medical Sciences (AMMS), Beijing, China. [Copyright &y& Elsevier]