Dataset Information

A controlled trial to assess the effect of quinine, chloroquine, amodiaquine, and artesunate on Loa loa microfilaremia.

ABSTRACT: Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species. A controlled trial was conducted to assess the effect of standard doses of quinine, chloroquine, amodiaquine, and artesunate on L. loa microfilaremia. Ninety-eight patients were randomly allocated into five groups (one for each drug and a control group) after stratification on microfilarial load. Loa loa microfilaremia was monitored on days 0, 3, 7, 15, 30, 60, and 90. No significant change in the loads was recorded in any of the treatment groups. A comprehensive review of the effects of antimalarial drugs against filariae is also provided.

SUBMITTER: Kamgno J

PROVIDER: S-EPMC2829896 | biostudies-other | 2010 Mar

REPOSITORIES: biostudies-other

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A controlled trial to assess the effect of quinine, chloroquine, amodiaquine, and artesunate on Loa loa microfilaremia.

Kamgno Joseph J Djomo Patrick Nguipdop PN Pion Sébastien D SD Thylefors Björn B Boussinesq Michel M

The American journal of tropical medicine and hygiene 20100301 3

Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species ...[more]

PMID: 20207860

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Project description:BackgroundPharmacokinetic (PK) and pharmacodynamic (PD) data are limited for artesunate (AS) and amodiaquine (AQ) in uncomplicated Plasmodium falciparum.MethodsFrom 2007-8, 54 P. falciparum-infected, Kenyan adults were assigned randomly fixed dose (FD) ASAQ (n?=?26) or non-fixed (NF) ASAQ (n?=?28). Total doses were 600 mg AS (both arms) + 1,620 mg (FD) or 1,836 mg (NF)AQ. Follow-up extended over 28 days. PK data were collected for AS, dihydroartemisinin (DHA), AS + DHA combined as DHA equivalents (DHAeq), AQ, desethylamodiaquine (DAQ),and their relationships assessed against the PD collected data consisting of parasitological efficacy, adverse events (AEs), and the Bazett's corrected QTinterval (QTcB).ResultsMean AUC 0-72 of dihydroartemisinin equivalents (DHAeq) when administered as a fixed dose (FD) compared to NF dose were similar: 24.2 ±4.6 vs 26.4±6.9 µmol*h/L (p?=?0.68) Parasite clearance rates were also similar after 24 hrs: 17/25 (68%) vs 18/28(64.3%) (p?=?0.86),as well as at 48 hrs: 25/8 (100%)vs 26 (92.9%)/28 (p?=?0.49). Mean FD vs NF DAQ AUC0-28 were 27.6±3.19 vs 32.7±5.53 mg*h/L (p?=?0.0005). Two PCR-proven new infections occurred on Day (D) 28 for estimated, in vivo, DAQ minimum inhibitory concentrations of 15.2 and 27.5 ng/mL. Combining the FD and NF arms, the mean QTcB at D2+4 hrs increased significantly (p?=?0.0059) vs baseline: 420 vs410 ms (??=?9.02 (95% confidence interval 2.72-15.31 ms), explained by falling heart rates, increasing DAQ concentrations and female sex in a general linear mixed effects model. Ten of 108 (9.26%) AEs (5/arm) reported by 37/54 (68.5%) patients were possibly or probably drug related. Severe, asymptomatic neutropaenia developed in 2/47 (4.25%) patients on D28: 574/µL (vsD0: 5,075/µL), and 777/µL (vsD0: 3,778/µL).ConclusionsTolerability of both formulations was good. For QTcB, a parameter for ECG modifications, increases were modest and due to rising DAQ concentrations and falling heart rates as malaria resolved. Rapid parasite clearance rates and no resistant infections suggest effective pharmacokinetics of both formulations.

Project description:Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemether-lumefantrine or artesunate-amodiaquine given with 50?mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunate-amodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264?h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624?h. Noncompartmental analysis was performed, and geometric mean ratios and 90% confidence intervals were generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, the time to maximum concentration, and the area under the concentration-time curve (AUC) for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine, nor did it significantly alter the AUC for artesunate, dihydroartemisinin, amodiaquine, and desethylamodiaquine. Coadministration of dolutegravir with artemether-lumefantrine resulted in a 37% decrease in DTG trough concentrations. Coadministration of dolutegravir with artesunate-amodiaquine resulted in 42 and 24% approximate decreases in the DTG trough concentrations and the AUC, respectively. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and dolutegravir exposure with artesunate-amodiaquine are unlikely to be of clinical significance since the DTG trough concentrations were above dolutegravir target concentrations of 300?ng/ml. Study drugs were well tolerated with no serious adverse events. Standard doses of artemether-lumefantrine and artesunate-amodiaquine should be used in patients receiving dolutegravir. (This study has been registered at ClinicalTrials.gov under identifier NCT02242799.).

Project description:The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children.We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate-mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876.Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate-mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76-91]) of 115 patients in the artesunate-mefloquine group versus 61 (55% [45-64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0-40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate-mefloquine than in those given chloroquine (18·0 h [range 6·0-48·0] vs 24·0 h [6·0-60·0]; p<0·0001), with faster clearance of ring stages in the artesunate-mefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9-9·4] vs 13·8 h [12·1-15·4]; p<0·0001). Risk of anaemia within 28 days was lower in patients in the artesunate-mefloquine group (71 [62%; 95% CI 52·2-70·6]) than in those in the chloroquine group (83 [75%; 65·6-82·5]; p=0·035). Gametocytaemia as detected by PCR for pks25 was present in 44 (86%) of 51 patients in the artesunate-mefloquine group and 41 (84%) of 49 patients in the chloroquine group at baseline, and in three (6%) of 49 patients and two (4%) of 48 patients, respectively, at day 7. Fever clearance was faster in the artesunate-mefloquine group (mean 11·5 h [95% CI 8·3-14·6]) than in the chloroquine group (14·8 h [11·7-17·8]; p=0·034). Bed occupancy was 2426 days per 1000 patients in the artesunate-mefloquine group versus 2828 days per 1000 patients in the chloroquine group (incidence rate ratio 0·858 [95% CI 0·812-0·906]; p<0·0001). One (<1%) patient in the artesunate-mefloquine group had a serious neuropsychiatric event regarded as probably related to study drug.Artesunate-mefloquine is highly efficacious for treatment of uncomplicated P knowlesi malaria. The rapid therapeutic response of the drug offers significant advantages compared with chloroquine monotherapy and supports a unified treatment policy for artemisinin-based combination therapy for all Plasmodium species in co-endemic areas.Malaysian Ministry of Health, Australian National Health and Medical Research Council, and Asia Pacific Malaria Elimination Network.

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Dataset Information

A controlled trial to assess the effect of quinine, chloroquine, amodiaquine, and artesunate on Loa loa microfilaremia.

Publications

A controlled trial to assess the effect of quinine, chloroquine, amodiaquine, and artesunate on Loa loa microfilaremia.

Similar Datasets

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