Antimicrobial activity of some medicinal plants

The FOLLOWING study was conducted to investigate the antibacterial activity of some medicinal plants. Ethanol extracts of different medicinal plants including Curcuma longa [Turmeric], Zingiber officinal [Ginger], Piper nigrum [Black Pepper], Cinnamomum cassia [Cinnamon], Thymus vulgaris [Thyme], Laurus nobilis [Bay leaf], and Syzgium aromaticum [Clove] were tested using the disc diffusion method for their antimicrobial activity against E. coli, S. typhimurium, E. faecium, and E. faecalis. Cinnamon extract [CE], at 130 micro g/disk, exhibited antibacterial activity against E. coli, S. typhimunium, and E. faecalis. Thyme extract [TE], at 30 micro g/disk, exhibited antibacterial activity against E. coli, E. faecium, and E. faecalis while the remaining medicinal plants extracts showed no activity. The minimum inhibitory concentration [MIC] of the cinnamon and thyme ranged from 31.25 to 250 micro g/ml by the dilution method. These results suggest that cinnamon and thyme have antibacterial activity in vitro

Randomized control trial of quinine and artesunate in complicated malaria.

OBJECTIVE: To study the comparative efficacy of the quinine and artesunate in complicated malaria in children. METHODS: All cases admitted to the Pediatrics ward of our hospital with clinical features of complicated malaria (WHO criteria) having asexual forms of P. falciparum in the peripheral smear, were included in the study. Relevant investigations were carried out for confirmation of diagnosis and to assess the prognosis. The patients were sub-grouped into 6 categories as per clinical presentations and each subgroup received alternatively either quinine or artesunate by systematic random sample method. Every odd number received quinine (Group-1) and every even number received artesunate (Group-2). 40 cases in each group were considered for the study and the data obtained were compiled and analyzed by suitable statistical tests. RESULTS: 80 children with complicated malaria enrolled in the present study, of which 48 were boys and 32 were girls. The mean age was 7.93+3.56 years. The most common presentations were fever, splenomegaly and altered sensorium. The CRT, FCT and PCT were significantly less in the artesunate group (50.4 +/- 31.49 hrs; 43.55 +/- 20.12 hrs, and 41.67 +/- 16.78 hrs respectively) as compared to the quinine group (70.15 +/- 17.56 hrs, 62.23 +/- 16.99 hrs, and 52.24 +/- 12.69 hrs respectively) ( p<0.05) No side effects were observed in the artesunate treated group. CONCLUSION: Artesunate is a much better drug than quinine in complicated malaria in terms of rapid coma resolution, fever clearance, parasite clearance and better tolerability.

Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria.

Plasmodium falciparum in Thailand is multi-drug resistant. In a previous study it was shown that artesunate and mefloquine were effective, as follow up, we monitored the efficacy of this regimen for six years. During 1997-2002, 516 adult male volunteer patients in Chanthaburi Province were enrolled (50 patients in the first year, 400 patients in 1998-2001 and 66 patients in 2002). The symptom complex and parasite count (thick blood film) were monitored on days 0, 1, 2, 7, 14, 21, 28, 35 and 42. The dosages used were artesunate (ATS) 150 mg and mefloquine (M) 750 mg at hour 0 and ATS 100 mg and M 500 mg at hour 24. Their ages ranged from 30-35 years and their mean body weights were 54-56 kg. The presenting symptoms were fever 100%, headache 97-100%, anorexia 78-90%, and nausea 28-40%. The geometric mean of parasitemia ranged from 7,357-12,750/mm3. Defervescence in one day was found in 42-76% of patients and 85-100% in 2 days. The sensitivity (S) ranged from 87-94% and RI resistance (recrudescence) ranged from 6-13%. Forty patients demonstrated RI type of response, 37 were cured after being retreated with the same dosage and another 3 patients were cured after the third course of treatment. The aggravated adverse effects included vomiting (8-20%), anorexia (1-41%) and diarrhea (0-16%). These side effects were mild and transient. The efficacy of the artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria was high. The RI type of response was possibly due to re-infection or multiple broods and not to drug resistance. The adverse effects of anorexia, nausea, vomiting and diarrhea were mild and transient for mefloquine. The combination can be used as stand by treatment in areas of multi-drug resistant falciparum malaria.

Post-marketing surveillance of arteether in malaria.

OBJECTIVE: To undertake post-marketing surveillance (PMS) of arteether (E-Mal) with the aim of obtaining feedback from clinicians regarding its safety, tolerability, efficacy and adverse event profile in patients of P. falciparum malaria. METHOD: Post-marketing surveillance proforma to collect data from clinicians using arteether (E-Mal) was provided to institutions/nursing homes and hospitals where Arteether (E-Mal) was available for use in treatment of P. falciparum malaria. These clinicians were informed about the need and relevance of providing this feedback regarding their reexperience on E-Mal therapy on predesigned proforma. Duly filled proformas were received by Central Drug Research Institute, Lucknow for data analysis, documentation and conclusions regarding E-Mal therapy. RESULT: A total of 300 reports were received for analysis from states of Bihar, Gujarat, Madhya Pradesh, Maharashtra, Rajasthan and Uttar Pradesh. The results show that 294 cases (98%) were cured, five cases improved and one patient did not show any change in the clinical status. The side effects (headache, nausea, vomiting and giddiness) reported in the proforma of 14 cases were mild in nature and no causal relationship with arteether could be ascertained. CONCLUSION: An indepth analysis of these 300 reports confirmed the safety, highlighted excellent tolerability and further proved the efficacy of three-day schedule of arteether (IMI) for treatment of malaria. Arteether should not be used in P. Vivax malaria (E-Mal) except when smear is positive for both (P. falciparum and P. vivax). In such a situation risk-benefit should be carefully evaluated before advocating the use of E-Mal therapy. The post-marketing surveillance is continuing and it is hoped that with more feedback from the clinicians from various parts of the country PMS data on this novel antimalarial drug (E-Mal) would further be documented.

Multicentric clinical trials for safety and efficacy evaluation of alpha;beta arteether in complicated P. falciparum malaria.

OBJECTIVE: To evaluate efficacy of alpha;beta arteether in patients of P. falciparum malaria presenting with complications was undertaken in a multicentric clinical trial. METHOD: Each patient who consented to undergo clinical trial with parenteral Arteether was treated with a fixed dose schedule of Arteether given intramuscularly in a dose of 150 mg once a day on three consecutive days. Every patient was followed upto 28 days with clinical, haematological and parasitological monitoring every day upto one week and thereafter at 14, 21 and 28 days. The response was assessed in terms of fever clearance time, parasite clearance time, cure rate and parasite reappearance rate. RESULTS: A total of 211 patients of P. falciparum malaria were included in the study from four centres (Bhilai, Guwahati, Jamshedpur and Rourkela). Results of this study showed that fever clearance time ranged between 24-168 hours, parasite clearance time ranged between 24-120 hours and overall mortality ranged between 4-8.5%. Out of 211, only 14 patients expired during the study, of these, 10 patients expired within first two days i.e. before completing the three day schedule of arteether therapy. Tolerability to arteether injection was good in all these patients and no untoward effects were experienced or reported during the study. Overall cure rate observed in these studies was 93%. CONCLUSION: This study shows a rapid parasite and fever clearance in patients of complicated P. falciparum malaria.

Artemether vs quinine therapy in Plasmodium falciparum malaria in Manipur--a preliminary report.

Qinghaosu and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant (sweet worm wood). Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of Plasmodium falciparum malaria. A randomised double blind trial was conducted in 52 cases of Plasmodium falciparum malaria cases. In all 26 cases were given artemether and another 26 were given quinine. There were 2 (7.5%) deaths in artemether group and 4 (15%) deaths in quinine group. The parasites were cleared more quickly from the blood in artemether group when compared to quinine group (mean-72 hrs vs 96 hrs). Resolution of fever was comparable in both artemether and quinine group (mean-84 hrs vs 78 hrs) and also the average time of recovery from coma was more earlier in artemether group (mean-60 hrs vs 72 hrs). The only side effect noticed with artemether therapy was gastrointestinal (GI) intolerance while quinine therapy was associated with myocarditis, hypotension, hypoglycemia and GI intolerance.

Effect of artemether on electrocardiogram in severe falciparum malaria.

The effect of intramuscular artemether (intramuscular loading dose of 160 mg, followed by 80 mg daily for another 6 doses), in comparison with that of quinine (intravenous infusion of loading dose of 20 mg/kg, followed by 10 mg/kg q 8 hourly for 7 days), on the electrocardiograph of severe falciparum malaria patients were investigated in 102 Thai patients (92 males, 10 females) admitted to Pra Pokklao Hospital, Chantaburi, southeast of Thailand. Fifty patients (19 with quinine and 31 with artemether) were eligible for ECG analysis. Hypotension was found significantly more common in the quinine group (13 vs 2 cases). Thirteen, 5 and 1 patients with quinine treatment, respectively, had tachycardia, non-specific T-wave change and QTc prolongation. No significant dysrhythmia was found despite high plasma quinine concentrations. Five patients died; their ECGs were not significantly different from those who survived. In the group with intramuscular artemether, 17 cases had tachycardia prior to artemether treatment. QTc prolongation and non-specific T-wave change were found in 2 and 6 cases. One patient had RBBB and second degree AV-block on Day 1, but returned to normal on Day 2. No other dysrhythmia or other significant changes in ECG tracing which would suggest any effect of artemether on cardiovascular system were observed.

Avaliação da eficácia do artesunato associado à tetraciclina na terapêutica da malária falciparum / The evaluation of the efficacy of artesunate combined with tetracycline in the therapy of falciparum malaria

Realizou-se um ensaio clínico, randomizado e controlado, comparando o artesunato com o quinino e a mefloquina, em casos de malária não grave. Foram tratados 42 pacientes em regime de internação e o seguimento durou 28 dias. Realizou-se exame de gota espessa cada 12 horas até sua negativação, hemograma e bioquímica sanguínea, pré e pós-tratamento. A média da parasitemia inicial foi 42.568 parasitas/ml. Vinte e seis pacientes foram acompanhados durante 28 dias e 16 durante menos de 28 dias. Um paciente de cada grupo apresentou R I tardia e um paciente do grupo do quinino apresentou R III. As porcentagens de cura foram 88,8%, 85,7% e 81,8% para o artesunato, a mefloquina e o quinino, respectivamente, sem mostrar diferença significativa. O tempo de desaparecimento da febre não mostrou diferença significativa entre os grupos. O grupo do artesunato teve um tempo menor de clareamento da parasitemia (37,33 ± 11,52 horas) quando comparado com o quinino (65,25 ± 17,44 horas), sendo estatisticamente significativa (p = 0,0016). O grupo da mefloquina (58,9 ± 16,68 horas) não mostrou diferença com os outros grupos. Não se apresentaram efeitos adversos importantes em nenhum dos esquemas usados, sendo bem tolerados pelos pacientes.

A controlled clinical therapeutic study in hospitalized patients compared artesunate with quinine and mefloquine in patients with uncomplicated falciparum malaria. Forty two patients entered the trial and the follow up was for 28 days with thick blood film taken every 12 hours until became negative. Laboratory examinations included haematological and biochemical tests before and after treatment. Patients had a mean parasitaemia of 42.568 per microliter. Twenty six patients completed 28 days of follow up but 16 did not fulfil this protocol. One in each of the therapeutic groups showed delayed R I resistance. A further patient in the quinine group showed R III resistance. The cure rate was 88.8% for artesunate. 85.7% for mefloquine and 81.8% for quinine; no significant difference was found, the same occurring with the clearance of fever. The artesunate group had a quicker parasitaemia clearance time (37.3 +/- 11.5 hours) when compared with quinine (65.2 +/- 17.4) showing a significant difference (p = 0.0016). Parasite clearance with mefloquine, was intermediate (58.9 +/- 16.6 ours) between the artesunate and quinine. No important side effects were observed with any of the therapeutic regimens and no deaths registered.

Estudo da eficácia e tolerância do artesunato oral isolado e em associaçäo com mefloquina, no tratamento da malária falciparum näo complicada em área endêmica do Pará, Brasil / An efficacy and tolerant study of oral artesunate alone and in combination with mefloquine in the treatment of uncomplicated falciparum malaria in an endemic area of Pará, Brazil

Com o objetivo de avaliar a eficácia e tolerância do artesunato no tratamento da malária falciparum nao complicada em área endêmica do Estado do Pará, 153 pacientes foram randomizados e estudados em três grupos, distribuídos por esquema terapêutico (I recebeu mefloquina l000mg; II utilizou artesunato l000mg; III usou a combinaçao de 600mg de artesunato seguida de 500 de mefloquina). A avaliaçao constou de exame clínico e parasitológico diariamente nos primeiros 7 dias e semanalmente até o 35§ dia do acompanhamento e de análise bioquímica e hematológica realizada antes e no 7§ dia, visando o controle de cura e a identificaçao de possíveis efeitos associados à administraçao das drogas. Os grupos estudados foram homogêneos quanto ao sexo, parasitemia e presença de febre. O tempo para desaparecimento da parasitemia foi mais curto nos grupos II e III, respectivamente, cujos esquemas terapêuticos empregaram artesunato. O desaparecimento da febre foi mais rápido no grupo tratado com a combinaçao das drogas. Alteraçoes clínicas e bioquímicas associadas a administraçao das drogas nao mostraram diferenças significativas entre os grupos estudados. O desaparecimento precoce da febre e parasitemia, e a ausência de importantes efeitos indesejáveis, sugerem que artesunato administrado isoladamente ou em combinaçao com mefloquina constituem medidas terapêuticas capazes de contribuir para o controle da doença na regiao.

Artemether-pyrimethamine in the treatment of pyrimethamine-resistant falciparum malaria.

In vitro susceptibility and clinical response of multidrug resistant Plasmodium falciparum to the combination artemether-pyrimethamine were evaluated in patients with acute uncomplicated falciparum malaria. Sixty patients were randomized to receive 3 oral regimens of the combination artemether-pyrimethamine as follows: Regimen-I: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then placebo on the two consecutive days; Regimen-II: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second day, and placebo on the third day; Regimen-III: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second and third days. All patients had a rapid initial response to treatments with 95% of parasitemia being cleared within the first 24 hours. PCT24hours and PCT48hours were similar among the three drug regimens (11 vs 4, 6 vs 12, and 9 vs 11 patients for a 1-day, 2-day, and 3-day combination regimen, respectively). Fever was cleared within 48 hours in all patients in either group. Transient mild nausea, vomiting and loss of appetite were found in a few patients during the first 2 days of treatment. Seven patients did not complete the 28 day follow-up period (5 vs 2 in a 1-day vs 2-day regimen), the reason for withdrawal was not associated with drug-related adverse effects. Only 53 patients were therefore qualified for the efficacy assessment. There was 15, 13 and 5 patients in a 1-day, 2-day and 3-day combination regimens, respectively, who had reappearance of the parasitemia between days 11 and 21. The cure rates of the 3 treatment groups were statistically significantly different (0, 27.8, and 75% for a 1-day, 2-day and 3-day combination regimen, respectively). Two patients developed P. vivax malaria on days 20 and 24. All of the isolates were highly resistant to pyrimethamine, with MIC of 10(-5) M. There is potential advantage of this combination therapy in reducing the dosage and treatment period of artemisinin derivative, which is therefore likely to improve complaince in clinical practice. The use of a 3-day combination regimen (300 mg artemether plus 100 mg pyrimethamine on the first day, then 150 mg artemether plus 50 mg pyrimethamine on the second and third days) seems to be a good alternative regimen to sulfadoxine/ pyrimethamine in areas where P. falciparum is sensitive to pyrimethamine eg in Africa.