Dihydroartemisinin-piperaquine for the routine treatment of uncomplicated malaria in Northern Ghana

Background:Dihydroartemisinin-piperaquine is a first line treatment for uncomplicated malaria in Ghana. A facility-based study was undertaken to examine the effectiveness of thetreatment in the routine health care system.Methods:The study was undertaken at the Navrongodemographic surveillance area. Patients presenting with acute febrile illness were enrolled after informed consented and confirmation by microscopy. Patients were randomized into supervised group who received treatment under direct observation and unsupervised group which had only the first treatment given under supervision. Treatment was according to bodyweight and 42 days follow-up was undertaken.Results:A total of 194 patients were enrolled; 54.1% were females and 51% had supervised treatment. The median age and weight were 6.7 years and 20.0kg respectively. Mean baseline temperature, haemoglobin concentration and parasite density were, 37.6oC, 11.1 g/dl and 11,098 parasites per microliter of blood respectively. Study completion rate was 93.3%, day 42 polymerase chain reaction-unadjusted adequate clinical and parasitological responses rate (ACPR) was 93.4% by evaluable and 87.1 % by intention-to-treat (ITT). The day 42 ACPR by evaluable was 92.3% in the supervised arm compared to 94.4% in the unsupervised arm. The day 42 ACPR by ITT was 85.7% in the supervised and 88.5% in the unsupervised arms. The fever resolution and haemoglobin concentration changes for the two arms were similar.Conclusions: The results show that dihydroartemisinin-piperaquine iseffective and good first-line antimalarial in the routine health delivery system

Patients experiences on the use of dihydroartemisinin piperaquine as an alternative first line artemisinin-based combination treatment for uncomplicated malaria in Northern Ghana

Background:Three different artemisinin-based combination therapies (ACTs) namely; artesunate-amodiaquine, artemether-lumefantrine and dihydroartemisinin-piperaquine (being the latest to be introduced) are concurrently being used forthe treatment of falciparummalaria in Ghana. This study assessed patients’ experience, perceptions and willingness to use dihydroartemisinin-piperaquine, brand name duo-cotecxin as an alternative first line ACT for the treatment of falciparummalaria in Northern Ghana.Methods:This was a qualitative study using phenomenology approach where sixty in-depth interviews were conducted with two groups; thirty patients who were given duo-cotecxin, one group and thirty interviews with patients who were given other ACTs (artesunate-amodiaquine, artemether-lumefantrine) as another group. The interviews were conducted between August and November, 2015 Purposive sampling technique was used to select study participants. The interviews were transcribed andcoded into themes using QSR NVivo 11 software for thematic content analysis.Results:All patients who used duo-cotecxin reported that the drug was very good in treating uncomplicated malaria compared to other ACTs they had used in the past. Some of the patients who used other ACTs could not complete their doses because of the side effects. However, none of the patients who used duo-cotecxin reported side effects. The findings revealed high acceptance and preference to use duo-cotecxin to treat uncomplicated malaria compared with other ACTs. All the participants were also willing to recommend duo-cotexcin to their relatives and friends to use. Conclusions: Duo-cotecxin as an alternative first line ACT for treatment of uncomplicated malaria is highly accepted, preferred and there was willingness to use it compared with other first line recommended ACTs.

Effect of artemisinin-piperaquine treatment on the electrocardiogram of malaria patients

Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.

Resistance of Plasmodium falciparum to artemisinin derivatives and piperaquine: Epidemic status and mechanism / 第二军医大学学报

Plasmodium falciparum is one of the main parasitic pathogens worldwide. Artemisinin derivatives are the first-line antimalarial drug. Recently, Plasmodium falciparum has been found to be tolerant to the treatment with artemisinin derivatives and its combination with piperaquine in several countries and regions. Scientists have found gene mutations associated with resistance of Plasmodium falciparum to artemisinin derivatives; however the mechanism of piperaquine resistance remains to be further studied. This review sums up the epidemic status and mechanism research of the resistance of Plasmodium falciparum to artemisinin derivatives and piperaquine.

Improvement of Determination Method for the Dissolution of Dihydroartemisinin in Dihydroartemisinin and Piperaquine Phosphate Tablets / 中国药房

OBJECTIVE:To improve the detection method for the dissolution of dihydroartemisinin in Dihydroartemisinin and piperaquine phosphate tablets. METHODS:The dissolution experiment adopted paddle method using 0.1 mol/L hydrochloric acid so-lution 500 mL as solvent with rotating speed of 75 r/min and sampling time of 45 min. In sample pre-treatment,the volume of 3.6% sodium hydroxide solution was increased from 5 mL to 20 mL,and that of phosphoric acid was increased from 0.2 mL to 0.7 mL. HPLC was adopted to determine the dissolution of dihydroartemisinin. The determination was performed on YMC-Pack ODS-A column with mobile phase consisted of 0.02 mol/L disodium hydrogen phosphate solution(pH adjusted to 2.4 using phosphoric ac-id)-acetonitrile(65 : 35,V/V)at the flow rate of 1.0 mL/min. The detection wavelength was set at 237 nm,and column temperature was 30 ℃. The sample size was 20 μL. RESULTS:The linear range of dihydroartemisinin were 7.802-117.03 μg/mL(r=0.9999). The limit of quantitation was 2.0 ng,and the limit of detection was 0.6 ng. RSDs of precision and reproducibility tests were all low-er than 1.0%. The recoveries were 99.18%-100.46%(RSD=0.45%,n=9). Average dissolutions of dihydroartemisinin in 3 batch-es of samples were 94.9%,77.9%,89.6%,respectively. CONCLUSIONS:Improved method enhance the accuracy for the limit of sensitivity,dissolution and detection results.

Short term treatment of uncomplicated falciparum malaria in Sierra Leone West Africa / 实用医学杂志

Objective To explore the short term treatment and highly effective treatment strategy for uncomplicated falciparum malaria in West Africa. Methods A total of 188 cases with uncomplicated falciparum malaria in the 34 Military Hospital in Sierra Leone and the tropical infectious disease prevention and control center of Chinese People′s Liberation Army and Sierra Leone Armed Forces from August 2016 to December 2016 were studied. All the patients were randomly divided into observation group A ,B and control group. Patients in group A were treated with oral artemether-lumefantrine tablets for 3 days,and the patients in group B were treated with oral dihydroartemisinin-piperaquine phosphate tablets for 2 days,while the control group patients received oral dihydro-artemisinin-piperaquine phosphate tablets for 7 days. The clinical efficacy ,recrudescence rate and adverse reaction were compared. Results The curative rates of observation group A ,B and the control group after the first course of treatment were 93.6%,95.2%,95.1%respectively,but there was no significant difference between groups(P>0.05). Recrudescence rate of group A was higher than that of the group B and the control group after 8 weeks follow-up,but the difference between groups was not statistically significant(P > 0.05). The incidence of drug adverse reaction in group A was the lowest among three groups ,and the difference was statistically significant compared with that of control group(P < 0.05). More patients in the control group manifested abnormal liver function with mild increased alanine aminotransferase level compared with patients in other groups at the end of treatment course. Conclusion Effectiveness of short term treatment with dihydroartemisinin-Piperaquine phosphate and Artemether-lumefantrine is obvious with lower adverse drug reaction in treating West Africa patients with uncomplicated falci-parum malaria.

Content Determination of Dihydroartemisinin in Dihydroartemisinin and Piperaquine Phosphate Tablets by HPLC / 中国药房

OBJECTIVE:To establish a method for content determination of dihydroartemisinin in Dihydroartemisinin and piper-aquine phosphate tablets. METHODS:HPLC was performed on the column of Waters YMC-Pack ODS-AQ with mobile phase of acetonitrile-water(gradient elution)at the flow rate of 1.0 ml/min,the detection wavelength was 216 nm,column temperature was 30℃,and injection volume was 20 μl. RESULTS:The linear range of dihydroartemisinin was 0.009 650-1.930 mg/ml(r=0.999 9);RSDs of precision,stability and reproducibility tests were no more than 0.5%;average recovery was 100.76%(RSD=0.95%,n=9). CONCLUSIONS:The method is simple,rapid and accurate,and can be used for the content determination of dihydroartemis-inin in Dihydroartemisinin and piperaquine phosphate tablets.

Determination of Content and Related Substances of Piperaquine in Artemisinin and Piperaquine Tablets by HPLC / 世界科学技术-中医药现代化

This study was aimed to establish determination method of content and related substances of piperaquine in A rtemisinin and Piperaquine Tablets, and to set the limit of related substance. HPLC was adopted on a SHISEIDO CAPCELL PAK C18 (4.6 mm í 250 mm, 5 μm) using an isocratic mobile phase consisted of acetonitrile: 0.1%trichloroaceticacid:triethylamine (18:82:0.2, V:V:V, pH 2.5) with a flow rate of 1.0 mL·min-1. The column tempera-ture was kept at 30oC and the detection wavelength was set at 216 and 237 nm, separately for the determination of related substance and content. The results showed that piperaquine and its related impurity can be separated effec-tively. The concentration-response relationship was linear over the range of 0.01-0.2 mg·mL-1 (R2=0.999 9). The av-erage recovery rate was 98.14% (RSD=0.77%, n=9). The minimum detection limit was 0.06 μg·mL-1. The solution was stable for 12 h. It was concluded that the method was specific, accurate, sensitive and suitable for the determi-nation of content and related substances of piperaquine in A rtemisinin and Piperaquine Tablets.

Discussion on Analysis of Artemisinin and Piperaquine Tablets by Infrared Spectroscopy / 世界科学技术-中医药现代化

Infrared (IR) spectroscopy was employed to identify the Artemisinin and Piperaquine Tablets. Artemisinin and piperaquine was extracted separately by different solvents, and IR spectra were collected. IR absorption spectrum of the extract was concordant with the reference spectrum recorded in the Atlas of Infrared Spectra of Drugs, except for a group of small absorptions at 1 574 cm-1 for the artemisinin extract. It was concluded that IR method is stable and accurate, which can be used to identify the Artemisinin and Piperaquine Tablets.

One-year Report on the Fast Elimination of Malaria by Source Eradication (FEMSE) Project in Moheli Island of Comoros / 广州中医药大学学报

Objective To investigate the therapeutic effect of the method of Fast Elimination of Malaria by Source Eradication (FEMSE) in Moheli island of Comoros. Methods Based on the FEMSE project, parasite positive cases were given a standard treatment course of ARTEQUICK (artemisinin plus piperaquine) plus primaquine: two tablets for adults at 0 hour and two tablets at 24 hours, a total of 4 tablets during one treatment course. One time of Mass Drug Administration (MDA) was for the children with parasite carrier rate less than 10%. Two times of MDA was for the children with parasite carrier rate more than 10%, and the interval between the two MDA was 42 days. Coverage rate for MDA and population carrier rate were observed. Results The number of people taking the first MDA of Artequick-Primaquine was 32,519 (the whole population registered at the same time being 37,243, 367 infants under 6 months old not involved), and the coverage rate for MDA was 88.2%. The population involved in the second MDA was 35,370 (the whole population registered at the same time being 37,112, 335 infants under 6 months old not involved), and the coverage rate for MDA was 96. 2%. Parasite carrier rate was 22.95% (281/ 1,224) before MDA, 1.41% (28/1, 987) two months after MDA and 0. 33% (8/2,458) four months after MDA, with a decrease of 98.56% . Conclusion The decrease of parasite carrier rate from 22. 95% to 0. 33% before and after MDA indicates that MDA of Artequick-Primaquine based on FEMSE can decrease the parasite carrier rate in a short time, without any obvious side effects. Further decrease of parasite carrier rate and incidence will be achieved if the measures for clearing malaria are fully implementated during the consolidation phase.

Pre-clinical & clinical trials of Arterakin (dihydroartemisinin-piperaquine) in treatment of uncomplicated malaria in Vietnam

A high therapeutic efficacy was found in the experimental mouse model infected with P. berghei (both chloroquin sensitive and resistant strains). At a low dose, as twice as the human dose and calculated as mg/kg of body weight of mice, the combination produced a high effect, clearing parasite within 3 days. However a considerable rate of recrudescence (10%) was found within 28 following-up days. At a high dose as tenth as a human dose, the combination was found to have a high therapeutic effect of 100% cure rate on mice clearing parasite within 2 days and no recurrence occured within 28 following-up days in all the tests. Arterakin was found to be a highly effective antimalaria drug with cure rate of 100% and a fast parasite clearance time (1-2 days) in both P falciparum and P. vivax infected patients. The total dose of 8 tablets for 3 days for adults and relevant doses for children appeared to be appropriate

Study on acute oral toxicities of Piperaquine phosphate and the fixed combination anti-malarial drug Dihydroartemisinin plus Piperaquine in mice

Background: Piperaquin (PQ) is an anti-malaria drug, which belong to bisquinoline class. Vietnam has successfully produced PQ (both base and phosphate) since 2004. Objective: To evaluate acute oral toxicities of Piperaquine phosphate and the fixed combination anti-malarial drug Dihydroartemisinin plus Piperaquine in mice. Subject and Method: This study was conducted at National Institute of Malariology, Parasitology and Entomology between June and October, 2005. The acute oral toxicities of piperaquine phosphate (PQP) and the fixed combination anti-malaria drug (40 mg dihydroiutemisinin plus 320 mg piperaquine phosphate (DHA-PQP), with the materials produced by Institute of chemistry) in mice were investigated. Result: PQP had a medium toxicity. Inhibition of mice's central nervous systems was the main toxicity exhibition. At the high doses of PQP, mice's convulsion was observed before their deaths. The infralethal dose (LDo), absolute lethal dose (LD100) and mean lethal dose (LD50) of PQP were 900, 2300 and 1643.98 (1537.6 \u2013 1758.92) mg/kg, respectively. The fixed combination DHA-PQP had a less toxicity than PQP powder, with LDo, LD100 and LD50 were 1400, 2800 and 2050.06 (1943.63 \u2013 2157.14) mg per kg of body weight, respectively. Conclusion: At the high doses of DHA-PQP, this combination also inhibited mice's central nervous systems. Mice convulsed strongly before their deaths. All died mice were operated for observing visually their organs such as hearts, livers, kidneys, lungs, vesicles and intestines. No abnormal signals were found.

Study on influences of the fixed combination anti-malarial drug dihydroartemisinin plus piperaquine in constitutions and some biochemical and haematological indices of rabbits

Background: The combination of dihydroartemisinin and piperaquine is interested because of its efficiency and safety in treating malaria. Objective: To evaluate the influences of the fixed combination anti-malarial drug dihydroartemisinin plus piperaquine in constitutions and some biochemical and haematological indices of rabbits. Subject and Method: The sub-chronic toxicity of the fixed combination anti-malarial drug of 40 mg dihydroartemisinin plus 320 mg piperaquine phosphate (DHA-PQP), with the materials produced by Institute of Chemistry, in rabbits was investigated. Rabbits were treated daily by oral route with DHA-PQP at the dose regimens of 64 and 100 mg/kg per day for 28 consecutive days. Result and Conclusion: DHA-PQP did not affect on rabbits' constitutions. Generally, all rabbits had normal ingestions, activities, and defecations. Rabbits' body weights increased regularly along the study period and significantly increased between day 28 and day 0 (P < 0.05). At the dose regimen of 64 mg/kg per day for 28 consecutive days, DHA-PQP did not change significantly rabbits' biochemical indices (including GOT, GPT, bilirubin, creatinine and protein) and haematological. These changes were insignificantly different between the treated and control groups at the same study points (P > 0.05). With the dose regimen of 100 mg/kg, the combination did not affect significantly (P>0.05) on some rabbits' biochemical and haematological indices. But hemoglobin, erythrocyte count and rate of monocytes increased significantly on day 14 comparing to that the control group (P < 0.05) and became in normal limits on day 29 (P > 0.05). Protein concentration also increased significantly on days 14 and 29 comparing to that of day 0 (P < 0.05).

Radomized clinical trials of dihydroartemisisnin - piperaquine against multi-drug resistant falciparum malaria in Viet Nam

A hospital based pilot study, conducted in a Tropical diseases hospital in Ho Chi Minh City of Viet Nam, compared the efficacy of three day regimens of dihydroartemisinin-trimethoprim-piperaquine (DTP total dose 4.7/13/47 mg/kg) with the standard antimalarial regimen in Vietnam, artersunate-mefloquine (A3M total dose 12/25 mg/kg) in non immune patients with uncomplicated falciparum malaria. 114 patients were enrolled (78 to the DTP arm and 36 to the A3M arm). The subsequent open randomised trial conducted at a Provincial Health Station compared DTP, dihydroartemisinin-piperaquine (DP) and A3M in 400 patients. In both studies all patients received derectly observed therapy and were followed for 56 days. The results: In the pilot study, the 56 day cure rate, adjusted for reinfections by PCR genotyping was 97.4% in the DTP group and 100% in the A3M group. In the second study, the cure rate were similar in each group. The DTP regimens were well tolerated, less than 3% of patients experienced possible drug related side effects compared with 16% of A3M patients

Therapeutic efficacy of dihydroartemisinin-piperaquin combination in malaria treatment in Vietnam

Therapeutic efficacy of dihydroartemisinin (DHA) - piperaquin in treatment of P falciparum and P. vivax was investigated in the National Institute of Malariology, Parasitology and Entomology (NIMPE), Hospital of Tropical Diseases in Ho Chi Minh city. Hospital inpatients and patients in primary health care facilities were enrolled in the study. Four small scale clinical studies were conducted and followed by large scale treatment studies in the Hospital of Tropical Diseases and primary health care services in the provinces of Binh Phuoc, Dak Lak, Quang Tri during the period 2001 - 2004. A total number of 3,978 malaria patients (989 P. vivax and 2,999 P falciparum were sampled

Study on influences of the fixed combination antimalaria drug dihydroartemisinin plus piperaquine in reproductive progress of mice

Background: Dihydroartemisinin 40mg and piperaquine phosphate 320mg (DHA-PQP) drug combination and piperaquin phosphate (PQP) material was first successfully produced in Vietnam \r\n', u'Objective: to study influences of the fixed combination antimalaria drug dihydroartemisinin plus piperaquine in reproductive progress of mice\r\n', u"Subjects and methods: This study was carried out at the Department of Malaria treatment and research, National Institute of Malariology, Parasitology and Entomology (NIMPE), between September, 2006 and March, 2007. The influences of the fixed combination antimalarial drug 40 mg dihydroartemisinin (DHA) plus 320 mg piperaquine phosphate (PQP), with PQP produced firstly in Vietnam, in mice's reproductive progresses were investigated in three generations (including the parent and FI, F2 child generations). \r\n", u'Results: In all three generations, study indices among the treated and control groups were not significantly different (the values P > 0.05). These indices included the rate of fecundation, numbers of fetuses of each mother mouse, numbers of offspring of each mother mouse, mean body weights of offspring. Early lethal fetuses, lately lethal fetuses, monsters and innate abnormally offspring were not found in P, FI and F2 generations. The necessary feeding - day numbers that offspring of P and F 1 generations reached their body weights about 20g were different insignificantly (the values P> 0.05) among the treated and control groups. \r\n', u'Conclusion: The combination DHA-PQP was found to cause no genome mutations in mice at the oral dose of 120 mg per kg per day for 5 consecutive days. \r\n', u'

Therapeutic effect of dihydroarteminsinin/piperaquine phosphate on Pneumocystis pneumonia in rat model / 中国血吸虫病防治杂志

Objective To research the therapeutic effect of dihydroarteminsinin/piperaquine phosphate(duo-cotecxin)on rats with Pneumocystis pneumonia(PCP),and explain its potential mechanism.Methods The PCP rat model was established through the subcutaneous injection with cortisone acetate twice a week for 6 weeks.The model rats were orally treated with duo-cotecxin at a dose of 40 mg/kg once a day for 3 days,and with cotecxin at a dose of 60 mg/kg once a day for 6 days,respectively.The therapy control group was treated orally with SMZco(sulfamethoxazol 250 mg/kg +Trimethoprim 50 mg/kg),positive control group and normal group were established,respectively.The drug efficacy was based on rat survival rate,increase rate of body weight,lung weight/body weight ratio,mean numbers of the cysts per field in the lung print smear,and the changes of CD4+ T cells,CD8+ T cells,NO,IFN-? and TNF-? in the blood.Results The survival rates and the body weight of rats treated with duo-cotecxin and cotecxin were higher and heavier than those of the positive control group respectively,which approached to those of the group treated with SMZco.The lung weight/body weight ratio,and mean cyst number per field of lung print smear of the rats treated with duo-cotecxin and cotecxin were lower than those of the positive control group,respectively.NO and TNF-? in the blood of the rats treated with duo-cotecxin and cotecxin were lower than those of the positive control group,respectively(P