Antimalarial

India, the country which incorporated its efforts towards (RAT) the innovation of light (AABHA) and that’s why it was named BHARAT. It depicts the country proceeding towards light of Truth (SAT), Consciousness (CHIT) and Bliss (ANANDA). Parallel to spiritualism, Indian Intelligentsia tried to protect the body from diseases, which is
supposed to be temple of God. Ayurveda is a holistic approach to cure the diseases by natural means. The Objectives of the work is to cover historical aspect of disease treatment in ancient India, to appreciate customs and practices prevalent in ancient Indian societies for malaria control which was primarily based on traditional knowledge system by carrying out multi-sectoral inter disciplinary work. It is tried depict the approach of ancient Indian wisdom in treatment of malaria by different means i.e. Ayurveda, Herbs, Yoga, Mudras etc. This shows the vastness of Indian understanding of health which is worth following by modern science. However, Modern medical science is now embracing ancient
Indian Health wisdom and pursuing enormous researches after experiencing inappropriateness of modern medical science. The burning example of it is AYUSH, to led researches in Ayurvedic, Yunani, Sindhi and Homeopathy ways of treatments.

This study evaluates the effect of ciprofloxacin (CIP) on the antimalarial activity of artesunate (AS), artemether-lumefantrine (AL) and artesunate-amodiaquine using animal model. Some 120 albino mice infected with chloroquine sensitive Plasmodium berghei NK65 strain were used. The study was carried out in three phases. Phase 1 consisted of eleven groups treated with different doses of either AS, AL, ASAQ or CIP alone. Phase 2 consisted of nine groups treated with 7 mg/kg of CIP (CIP1) combined with different doses of AS, AL, ASAQ. Phase 3 consist of ten groups treated with 14 mg/kg of CIP (CIP2) with different doses of AS, AL, ASAQ. Thin blood films were used to assess parasitemia level daily after administration of drugs for 72 h. Results were analyzed using student t-test and analysis of variance (ANOVA). CIP alone showed antimalarial activity with 63 % parasitemia reduction. Antimalarial activities of AS and AL were significantly enhanced by both 7 and 14 mg/kg of CIP. The antimalarial effect of ASAQ was enhanced but not statistically significant. Low dose ciprofloxacin significantly enhanced the antimalarial activities of Artesunate, Artemether-Lumefanthrine and Artesunate-Amodiaquine This combination may be beneficial in the management of Plasmodium falciparum infection or co-infection with salmonellosis.

In the current work, we discovered and analyzed the epidemiological paradox between coronavirus disease 2019 (COVID-19) and malaria in the initial phase of the ongoing pandemic. From the analysis of distribution data, the endemic presence of malaria seems to protect some populations from COVID-19 outbreak, particularly in the least developed countries. In this sense, molecular and genetic variations associated with malaria (e.g., in ACE2) might play a protective role against coronavirus infection. Moreover, the mechanism of action of some antimalarial drugs, e.g., the antiviral function, suggests their potential role in the chemoprophylaxis of coronavirus epidemics, despite possible adverse effects (e.g., retinal toxicity). All these data provide important insights to understand the spreading mechanisms of COVID-19, and to direct scientific research toward the study of some currently available medications.

In this short review, the current knowledge on the chemical constituents and anticancer properties of Cerbera odollam and Cerbera manghas is updated with some description of their botany and uses. Although these two closely-related coastal tree species have overlapping geographical distribution, they can be distinguished by the eye colour of flowers and the shape of fruits. Chemical constituents of C. odollam and C. manghas include lignans, iridoids, terpenoids, cardiac glycosides (cardenolides), flavonoids, phenolic acids and steroids. Cardiac glycosides of cerberin, dehydrocerberin, neriifolin, tanghinin, deacetyltanghinin and tanghinigenin possess promising anticancer properties with apoptotic activities. However, these cardiac glycosides are also cardiotoxic. Fatal cases of suicides by ingesting Cerbera fruits or seeds have been reported in India and Sri Lanka. In two suicide cases, one in Taiwan and another in the United States, the patients recovered completely. In New Caledonia, four death-threatening cases of poisoning (two were fatal) occurred through consuming toxic coconut crabs. Taken together, both C. odollam and C. manghas are endowed with cardiac glycosides, which have useful pharmacological properties but lethal toxicity.

The essential oils of the plant Deverra scoparia Coss. & Dur. (Apiaceae) used in traditional medicine in Algeria were subjected to testing the antimalarial activity. Their potential ability to inhibit the in vitro proliferation was evaluated in two strains of Plasmodium falciparum; chloroquine-resistant (K1), and chloroquine-sensitive (3d7) strains. The essential oils displayed good antimalarial activity with IC50 values 1.51 ± 0.71 μg/mL and 0.93 ± 0.89 μg/mL against the 3d7 chloroquine-sensitive and the K1 chloroquine-resistantstrains respectively. So, Deverra scoparia presented a potential source of antimalarial molecules.

Eur J Clin Pharmacol 1991, 41(4) 383-5. The itching induced by full antimalarial doses of chloroquine was attenuated or prevented  both by prednisolone 5mg and niacin 50mg compared to placebo in a randomized controlled trial.  There was a significant reduction in the AUC 0-72hr by the drugs.  There was an indication that the itching severity was related to the malaria parasite load in blood. This study provided preliminary evidence that prednisolone may attenuate itching due to chloroquine, without affecting malaria parasite clearance or clinical recovery from malaria fever.

One new protoberberine alkaloid, which we named as simplicifolianine after its species, was isolated from Meconopsis simplicifolia. This compound exhibited significant antimalarial activities against multidrug resistant strain K1CB1 and chloroquine sensitive strain, TM4 of Plasmodium falciparum

Bioreducible indolone-N-oxides have demonstrated their potent antimalarial activities with, however, a short half-life. The deoxygenated analogues, 2-aryl-3H-indol-3-ones, a reduced chemical form obtained by synthesis, have similar antiplasmodial properties against the blood stages of Plasmodium falciparum in vitro, with, however, a low aqueous solubility in vivo. Albumin-based nanosuspensions were used to solubilize these new compounds to conduct experiments in vivo using the P. berghei ANKA murine model to determine the antimalarial activity of the most active derivative of this deoxygenated series, the 5-methoxy-2-(4- methoxyphenyl)-3H-indol-3-one (IND-1). Results were compared with its oxygenated analogue tested in the same conditions. Albumin-based nano-suspensions were prepared by precipitation, high-pressure homogenization and lyophilisation to yield nanoparticles of controlled diameter (350 nm) and polydispersity index (0.223) suitable for intravenous administration. The efficacy of IND-1, free and formulated in albumin-based nanosuspensions, was evaluated on a murine model infected with P. berghei ANKA. Assays revealed that the nanoformulation is much more potent (ED50 7.3 mg/kg/day, ip) than the non-formulated IND-1 (ED50 49.5 mg/kg/day, ip). Moreover, the albumin-based formulated nanosuspensions of IND-1 showed 100 % parasitemia inhibition when administered iv and ip at 50 and 100 mg/kg/day, respectively. This inhibition was not reached with the classical solvent/cosolvent methods. In conclusion, the albumin-based nanosuspensions of 2-aryl-3H-indol-3-ones greatly enhanced their antimalarial activities in vivo with a 7-fold decrease of the ED50 on ip administration compared to the free compound. However, the reduction of the NO moiety did not significantly improve in vivo properties of the IND-1 compound compared, in the same conditions, to the INOD-1 compound.

An investigation of the essential oil (EO) and the crude MeOH extract of a Bhutanese variety of Ajania nubigena using GC/GC-MS and NMR found the
following: a) one kg of the dried plant material contained 0.7% w/w EO; b) 44 of the 53 GC-FID peaks of the EO were identified with (3R,6R)-linalool oxide
acetate (75.8 %) as the major constituent (chemotype II) and chamazulene as a new sub-chemotype; c) purification of the EO furnished (3R,6R)-linalool oxide
acetate (1), chamazulene (2), (E)-2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4,4]non-3-ene (3), and (Z)-2-(2,4-hexadinylidene)-1,6-dioxaspiro[4,4]non-3-ene (4);
d) from the crude MeOH extract, four flavonoid compounds: 1-(4-hydroxyphenyl)propan-1-one (5), oxyanin B (6), luteolin (7) (major) and the luteolin-7-O-β-
D-glucoside (8) were isolated; e) among the EO and pure compounds tested for biological activities, compound 7 exhibited a broad range of moderate
antiplasmodial, cytoxicity and antimicrobial activities; c) compound 8 showed significant in vitro antiplasmodial activity against P. falciparum strains TM4/8.2
and K1CB1 (multidrug resistant strain) and was identified as a potential antimalarial scaffold; and f) the in vitro antimicrobial and cytotoxicity activities were
in alignment with the traditional medical uses of this plant and thus substantiate its use in Bhutanese traditional medicine.

Introduction
As a response to the anti-malarial drug resistance situation, the
World Health Organisation (WHO) recommends that treatment
policies for falciparum malaria in all countries experiencing
resistance to monotherapies should be combination therapies,
preferably those containing an arteminisin derivative (ACTartemisinin-
based combination therapy).
Methodology
A retrospective quantitative study was designed to examine case
records of patients treated for malaria in a tertiary health hospital
in Jos, Northern part of Nigeria between August and December
2012. Questionaires were also distributed to doctors working
within the hospital environment. Data on demographic, clinical
features of disease, diagnostic procedures and drug administration
were collected from the patients' records.
Results
Case record files of 130 patients were selected, 80.7% of the
patients were prescribed antimalarial drugs. 55.2% of patients
admitted for malaria were males, 44.8% were between 21-50 years
of age. Fever (35.2%) was the most common presenting symptom,
71.4% of the patients had diagnostic blood slides. Antimalarial
drugs were prescribed for malaria and malaria associated with
other disease conditions, artemisinin and lumefantrine was the
most prescribed antimalarial agent. 44.0% of these drugs were
prescribed by trade names, 29.0% were administered orally. The
most antimalarial drug prescribed for prevention of malaria in
pregnant women was sulfadoxine-pyrimethamine, all the
practitioners followed current WHO guidelines , half of the
clinicians would prescribe parenteral antimalarial drugs for severe
and cerebral malaria, laboratory and clinical assessment were used
for malaria diagnosis, 71.4% of the physicians adhered to hospital
guidelines.
Conclusion
This study indicates the implementation of artemisinin
combination therapy in a public health facility; however the
success of this new treatment policy would depend on patient
adherence to recommendations and provision of ACTs at
subsidized costs in Nigeria.

The use of plant to meet health-care needs has greatly increased worldwide in the recent times. The search for new plant-derived bioactive agents that can be explored for the treatment of drug-resistant malaria infection is urgently needed. Thus, we evaluated the antimalarial activity of three medicinal plants used in Nigerian folklore for the treatment of malaria infection. A modified Peter's 4-day suppressive test was used to evaluate the antimalarial activity of the plant extracts in a mouse model of chloroquine-resistant Plasmodium berghei ANKA strain. Animals were treated with 250, 500, or 800 mg/kg of aqueous extract. It was observed that of all the three plants studied, Markhamia tomentosa showed the highest chemosuppression of parasites of 73 % followed by Polyalthia longifolia (53 %) at day 4. All the doses tested were well tolerated. Percentage suppression of parasite growth on day 4 post-infection ranged from 1 to 73 % in mice infected with P. berghei and treated with extracts when compared with chloroquine diphosphate, the standard reference drug which had a chemosuppression of 90 %. The percentage survival of mice that received extract ranged from 0 to 60 % (increased as the dose increases to 800 mg/kg). Phytochemical analysis revealed the presence of tannins, saponins, and phenolic compounds in all the three plants tested.

Corydalis dubia was studied phytochemically and pharmacologically. One new natural product was discovered and scoulerine showed significant antimalarial activity against multi-drug resistant Plasmodium falciparum strains, K1CB1 and chloroquine sensitive strain TM4.

A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold. Additionally, Mannich-base derivatives, containing a 7-aminomethyl-6-hydroxy substitution pattern at ring A, were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2, two validated targets expressed during the blood stage of P. falciparum infection and functional in digestive vacuole of the parasite. Overall, this study highlight (i) the usefulness of aurones as platforms for synthetic procedures using palladium catalyzed protocols to rapidly deliver lead compounds for further optimization and (ii) the potential of novel aurone derivatives as promising antimalarial compounds.

Context: Garcinia kola seeds are widely used in Congolese traditional medicine to treat uncomplicated malaria. While the ethanolic extract of these seeds (GK) is reputed for oral antimalarial activity, some of its constituents have shown poor water solubility, which might compromise further phytopharmaceutical developments. Aims: To develop a self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of GK, since SNEDDS are promising vehicles for enhancing drug product solubility. Methods: GK was loaded into liquid SNEDDS (solution and suspension) and solid SNEDDS (S-SNEDDS), and the resultant formulations were characterized using dynamic light scattering and electron microscopy. The antimalarial activity of SNEDDS (200 mg/kg × 4 days, oral) was evaluated in Plasmodium berghei-infected mice using a conventional four-day suppressive test. Results: The characterization of SNEDDS formulations revealed the presence of nanosized structures of spherical morphology and negative surface charge. Data from in vivo study showed reduced parasite growth by 77.9, 73.8 and 74.2% for GK-SNEDDS solution, GK-SNEDDS suspension and GK-S-SNEDDS, respectively. The activity of GK-SNEDDS was found to be greater than that of a licensed GK-based syrup (N'sansiphos®) used at the same dose (p<0.05). Conclusions: These findings demonstrate the potential of SNEDDS formulations as a promising alternative for enhancing the antimalarial efficacy of GK following oral administration. The SNEDDS technology holds the promise of improving the oral delivery of herbal-based products for malaria therapy.

Various heterocyclic compounds along their derivatives were evaluated for their biological activities as antiviral, antitumor, anticonvulsant, antibacterial, antifungal, antituberculosis, analgesic, anti-inflammatory, antidiabetic, antihistamine and other biological activities. The triazole moiety seems to be very small, but in the biological profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. The triazole derivatives possess a great importance in medicinal chemistry and can be used for the synthesis of numerous heterocyclic compounds with different biological activities. This review article covers the information of triazoles derivatives having different psychopharmacological actions. Thus triazole acts as a promising medicinal agent for the scientists working over this field. This review can be helpful to develop various more new compounds possessing triazoles moiety that could be better in terms of efficacy and lesser toxicity.

The evolution and subsequent design of clinically effective antima-larial drugs particularly 4-aminoquinolines, 8-aminoquinolines and 9-amino-acridines are reviewed. These molecules benefited from scientific advances in medicinal and synthetic chemistry guided by pharmacological screening, including animal models of malaria. The mechanism of action of antimalarials, especially against the heme receptor, and the impact of this knowledge on drug design is critically discussed. Modelling investigations and quantum mechanics calculations reveal close contacts between the porphyrin ring and selected atoms within compounds such as the bisquinoline, metaquine. Analysis of these close contacts can be used to design compounds with modulated antimalari-al activity to further clarify the drug action. Knowledge of mammalian drug metabolism and pharmacokinetics, together with detailed in vitro and in vivo pharmacology has aided (a) resurrection of old compounds and (b) redesign of existing compounds. The latter includes judicious modification (e.g. inversion of oxidizable functional groups as in SN-13,730 i.e. isoquine) or introduction of groups blocking metabolism (e.g. exploiting bond strength viz. fluorine or steric effects with the t-butyl group). This simultaneous modulation of both drug metabolism and interaction with the heme receptor can be used to enhance antimalarial activity. Compounds benefiting from such modifications include primaquine, pyronaridine, isoquine, metaquine and AQ-13, together with selected analogues with useful activity against drug-resistant Plasmodia in vi-vo. It is concluded that optimisation of the privileged quinoline and acridine scaffolds, discovered in the early part of the 20 th century, still has a vital role to play in the future discovery of cost effective solutions to malaria.

In 2010, malaria was responsible for an estimated 41% of deaths among children under the age of five years in Liberia. The same year, the Rebuilding Basic Health Services Project launched &quot;Healthy Baby, Happy Mother,&quot; a social and behavior change communication campaign. The campaign encouraged caregivers to take children under the age of five years to a health facility as soon as children developed fever. This study investigated correlates of two case management outcomes: care-seeking for children under five with fever during the past two weeks and administration of an artemisinin-based combination therapy (ACT) the same or next day as fever onset. Data from a 2014 cross-sectional household survey from four counties was used to investigate correlates of two case management outcomes. Using multilevel analysis, the association between these outcomes and a caregiver&#39;s recall of the campaign, her sociodemographic characteristics, and unmeasured characteristics of the commu...

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N′-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (di-hydrochloride), which is active against Plasmodium berghei in vivo (oral ID 50 of 25 µmol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 µM). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1:1 ratio (log K) 5.7 (0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.

The artemisinins are the most effective antimalarial drugs known. They possess a remarkably wide therapeutic index. These agents have been used in traditional Chinese herbal medicine for more than 2,000 years but were not subjected to scientific scrutiny until the 1970s. The first formal clinical trials of the artemisinins, and the development of methods for their industrial scale production, followed rapidly. A decade later, Chinese scientists shared their findings with the rest of the world; since then, a significant body of international trial evidence has confirmed these drugs to be far superior to any available alternatives. In particular, they have the ability to rapidly kill a broad range of asexual parasite stages at safe concentrations that are consistently achievable via standard dosing regimens. As their half-life is very short, there was also thought to be a low risk of resistance. These discoveries coincided with the appearance and spread of resistance to all the other major classes of antimalarials. As a result, the artemisinins now form an essential element of recommended first-line antimalarial treatment regimens worldwide. To minimize the risk of artemisinin resistance, they are recommended to be used to treat uncomplicated malaria in combination with other antimalarials as artemisinin combination therapies (ACTs). Their rollout has resulted in documented reductions in malaria prevalence in a number of African and Asian countries. Unfortunately, there are already worrisome early signs of artemisinin resistance appearing in western Cambodia. If this resistance were to spread, it would be disastrous for malaria control efforts worldwide. The enormous challenge for the international community is how to avert this catastrophe and preserve the effectiveness of this antimalarial “magic bullet”. Drug Dev Res 71: 12–19, 2010. © 2009 Wiley-Liss, Inc.

Malaria is responsible for about a million deaths yearly. The fight against malaria is faced with the occurrence of widespread resistance of the malaria parasite, Plasmodium spp. The search for plant derived anti-malarial drugs has become greatly imperative. This study was aimed to isolate and investigate the In vivo anti-malarial activity of pulcherrimin A isolated from the stem bark of Caesalpinia pulcherrima. Ethyl acetate fraction of the stem bark extract was subjected to fractionation over silica gel column to obtain pure compound which was characterized as 3,5,6,7-tetrahydroxy-19-vouacanoic acid;(3β,5α,6β,7β)-form,6,7-dibenzoyl (pulcherrimin A) a known compound using various spectroscopic techniques. Pulcherrimin A was evaluated for In vivo anti-malarial activity against P. berghe infected mice using the 4-day suppressive test. Different doses (50, 200 and 400 mg/kg/day) of pulcherrimin A were administered to the mice after parasite inoculation. A maximum parasitaemia suppress...

In 2010, malaria was responsible for an estimated 41% of deaths among children under the age of five years in Liberia. The same year, the Rebuilding Basic Health Services Project launched &quot;Healthy Baby, Happy Mother,&quot; a social and behavior change communication campaign. The campaign encouraged caregivers to take children under the age of five years to a health facility as soon as children developed fever. This study investigated correlates of two case management outcomes: care-seeking for children under five with fever during the past two weeks and administration of an artemisinin-based combination therapy (ACT) the same or next day as fever onset. Data from a 2014 cross-sectional household survey from four counties was used to investigate correlates of two case management outcomes. Using multilevel analysis, the association between these outcomes and a caregiver&#39;s recall of the campaign, her sociodemographic characteristics, and unmeasured characteristics of the commu...

Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic
extract of the husk fire of Dwarf Red variety of Cocos nucifera were evaluated in this study.The dried powdered husk fire was exhaustively extracted with hexane, ethyl acetate, and methanol successively and the methanolic extract was screened for flavonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei, NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight (BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d. Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics,
saponins, glycosides, steroids, and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered (P>0.05) at all doses of the extract, except red blood cell count which was significantly elevated (P<0.05) at 100 mg/kg BW. The extract significantly increased (P<0.05) urea, creatinine, cholesterol, high-density, lipoprotein-cholesterol, and bilirubin concentrations in the serum as well as the atherogenic index, while it reduced albumin concentration significantly (P<0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart significantly (P<0.05) but was increased in the serum significantly (P<0.05) at higher doses of the extract compared to the controls. The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to  cardiovascular diseases

Copaifera langsdorffii Desf. is a medicinal plant found in all regions of Brazil. Copaiba oleoresin is widely trade around the world and well-known for its distinct biological properties. The present work reports the isolation of compounds from leaves, fruits and flowers of Copaifera langsdorffii, as well as in vitro leishmanicidal and antimalarial assays with the crude hydroalcoholic extracts from leaves, fruits and flowers. The hydroalcoholic crude extracts were chromatographed using silica gel by classic chromatography, and purified by preparative TLC. HPLC-DAD was used to purify the polar compounds. The thermally stable compounds were evaluated by GC/MS. NMR and mass spectrometry data were used to establish the chemical structures. Nine compounds were isolated and identified: 1: kaurenoic acid, 2: ent-labda-7,13-dien-15-oic acid, 3: (E)-2-ethoxyvinylphenol, 4: 2-hydroxy-ent-labda-7,13-dien-15-oic acid, 5: caryophyllene oxide, 6: kaurenol, 7: ethyl 4-hydroxylcinnamate (semisynthetic 4-methylated form of compound 7 was isolated), 8: quercetin-3-O-α-L-rhamnopyranoside (quercitrin), and 9: kaempferol-3-O-α-L-rhamnopyranoside (afzelin), and a new compound (3) from fruits. Compounds 4 and 7 were reported for the first time in the aerial parts of Copaifera genus. Kaurenoic acid and β-caryophyllene were major compounds in all samples studied. Flavonoids 8 and 9 were major phenolics in the leaves hydroalcoholic extract. The Fruits extract displayed antileishmanial activity against Leishmania donovani with IC 50 of 40 µg/mL. Leaves and flowers extract displayed antimalarial activity with IC 50 of 3.4 and 6.2 µg/mL, respectively for different clones of Plasmodium falciparum. In addition, none of the tested samples displayed cytotoxicity against mammalian Vero cells.

The aim of this study was to assess the antimalarial activity of nine medicinal plants used by Karens of Andaman and Nicobar Islands, against Plasmodium falciparum chloroquine-sensitive MRC-2 isolate. The methanol extracts were obtained by cold percolation method and in vitro antimalarial activity was assessed using M-III method. The results indicated that out of nine plant species tested, four plants, viz., Z. spectabilis, S. wallichiana, C. pulcherrima and Amomum sp. demonstrated significant antimalarial activity (50% inhibitory concentration values were 5.5 ± 0.7, 12.0 ± 2.5, 14.6 ± 1.3 and 37.3 ± 2.5 μg/mL respectively) with no toxicity effect on erythrocytes.

BACKGROUND:
Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.

METHODS:
Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.

RESULTS:
Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites.

CONCLUSIONS:
There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.