Anti-tuberculosis activities of the crude methanolic extract and purified fractions of the bulb of Crinum jagus

Summary: Tuberculosis (TB) is of great public health burden globally especially in developing countries of Africa and Asia . Current TB regimen involves multiple therapies and of long duration leading to poor patient adherence. There is also the challenge of multidrug resistant TB. Hence, there is a need for discovery of new anti- TB drugs. This study was designed to investigate the in –vitro activity of the crude methanolic extract and chromatographic fractions of the bulb of Crinum jagus against Mycobacterium tuberculosis isolates. The extracts were screened for anti- TB activity against three different M. tuberculosis isolates and a drug susceptible reference strain H37Rv using Lowenstein Jensen (L-J) medium and Middlebrook 7H10agar. The crude extract was prepared using soxhlet extraction apparatus while the purified fractions were obtained by column chromatography. The two media were inoculated with M. tuberculosis strains, after which the crude and purified extracts were added. After 4-6 weeks incubation, colony forming units were counted and percentage inhibition calculated. The crude extract and the purified fractions showed inhibitory activity on all the isolates tested including the reference strain. Fraction 3 showed the highest inhibitory percentage (86%) among the extracts. At a concentration of 1.0mg/ml, the percentage inhibition of fraction 3, rifampicin and isoniazid against M. tuberculosis strain 3 were 83%, 95% and 86% in L-J medium respectively while 86%, 96% and 89% were obtained respectively in Middle brook medium. Results showed that the crude methanolic extract and the purified fractions of the bulb of Crinum jagus exhibited anti-mycobacterial activity which is an indication of promising potential of this plant for the development of anti-tuberculosis agent.Keywords: Crinum jagus, Chromatographic fractions, Mycobacterium tuberculosis, In-vitr

Evaluation of the comparative efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and artesunate-amodiaquine-chlorpheniramine (Artemoclo™) for the treatment of acute uncomplicated malaria in Nigerian children.

OBJECTIVE: To evaluate the comparative efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and artesunate-amodiaquine-chlorpheniramine (AQC) for the treatment of acute uncomplicated malaria among Southwest Nigerian children. SUBJECTS AND METHODS: One hundred and sixty children aged 6 months to 14 years with acute uncomplicated malaria were randomized to AL (n = 53), ASAQ (n = 53), or AQC (n = 54). Enrollees were seen daily on days 0-3 and then on days 7, 14, 21, 28 and 42 for clinical and parasitological evaluations. Paired samples of genomic DNA at enrolment and at the time of recurrent parasitaemia were genotyped using nested PCR to distinguish between reinfection and recrudescence. Detailed haematological and biochemical evaluations were carried out in a subset of enrollees on days 0, 7 and 28 as part of a safety evaluation. RESULTS: Of the 160 children, 144 (90%) completed the study. The mean fever clearance times and parasite clearance times for AL, ASAQ and AQC were comparable (p = 0.94 and p = 0.122, respectively). On day 14, the adequate clinical and parasitological response (ACPR) for AL and AQC was 100% and for ASAQ it was 90% (p = 0.39). The PCR-uncorrected results on days 28 and 42 and the ACPR-corrected results on day 42 were similar for all drugs (p = 0.62 and p = 0.56, respectively). AQC resulted in the best parasite clearance and haematological recovery on day 2 (p = 0.022 and p = 0.018, respectively). Biochemical parameters were not adversely affected by the three artemisinin-based combination therapies (ACTs) and these were well tolerated. CONCLUSION: The three ACTs were efficacious and safe, but AQC resulted in a better haematological recovery on day 2 and higher cure rates throughout the study period

An open randomized clinical trial in comparing two artesunate-based combination treatments on Plasmodium falciparum malaria in Nigerian children: artesunate/sulphamethoxypyrazine/pyrimethamine (fixed dose over 24 hours) versus artesunate/amodiaquine (fixed dose over 48 hours)

<p>Abstract</p> <p>Background</p> <p>Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance.</p> <p>Methods</p> <p>Children aged one year to 13 years presenting with uncomplicated <it>Plasmodium falciparum </it>malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP) (12 hourly doses over 24 hours) or three doses of artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response.</p> <p>Results</p> <p>There were two (0.4%) early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the AS + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p = 0.021). The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The parasite clearance time was also similar in the two treatment groups with 1 - 7 days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941). The proportion of children with gametocytes over the follow-up period was similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin) remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS + SMP group.</p> <p>Conclusions</p> <p>This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval) for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS + SMP could be an alternative to currently recommended first-line ACT with continuous resistance surveillance.</p

Chlorproguanil−Dapsone−Artesunate versus Artemether−Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria

Chlorproguanil−dapsone−artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether−lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients

Prevalence and molecular characterization of Glucose-6-Phosphate dehydrogenase deficient variants among the Kurdish population of Northern Iraq

<p>Abstract</p> <p>Background</p> <p>Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds.</p> <p>Methods</p> <p>A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C→T), G6PD Chatham (1003 G→A), G6PD A- (202 G→A), G6PD Aures (143 T→C) and G6PD Cosenza (1376 G→C), as well as the silent 1311 (C→T) mutation.</p> <p>Results</p> <p>Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and 10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases.</p> <p>Conclusions</p> <p>The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to those reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries.</p

In vitro antimalarial activity of methylene blue against field isolates of Plasmodium falciparum from children in Southwest Nigeria.

BACKGROUND & OBJECTIVES: Methylene blue (MB), a thiazine dye is used in the treatment of various methemoglobinaemias. However, sporadic reports have shown some antimalarial therapeutic effect when administered to patients with clinical manifestations of malaria. The inhibitory concentration of schizont maturation and antimalarial activity of MB have not been fully elucidated. The present study therefore aimed at determining the antimalarial activity of MB in Plasmodium falciparum isolates obtained from children with malaria using standard in vitro drug susceptibility test. METHODS: Twenty children (8 boys and 12 girls) within the age range 4.5-11.5 yr were enrolled into the study and 2 ml of blood withdrawn aseptically. The standard microtest technique of schizont inhibition assay was used to culture fresh isolates obtained from P. falciparum infected patients. Chloroquine (CQ) and quinine (QN) were used as reference standards for in vitro drug susceptibility tests. RESULTS: The mean 50 per cent inhibitory concentration (IC(50)) values were 9.59 +/- 3.25nM, 196 +/-21.11nM and 607 +/- 27.41nM for MB, CQ and QN respectively. Ten of the 14 isolates were sensitiveto MB, 11 were sensitive to CQ while nine were sensitive to QN. Three isolates were resistant to CQ,and of these, two were sensitive to MB and one was sensitive to QN. INTERPRETATION & CONCLUSION: This preliminary study showed that MB has high antimalarial activity comparable with CQ and QN and may be used as a potent schizonticidal drug against CQ-resistant isolates

Effect of Antimalarial Drugs and Malaria Infection on Oxidative Stress in Pregnant Women

This work studied the effect of malaria infection and antimalarial drugs on oxidative stress in 259 pregnant and non-pregnant women at Ade-Oyo hospital, Ibadan, Nigeria. Oxidative stress was determined by measuring serum lipid peroxidation, ascorbic acid, and reduced glutathione (GSH) levels using spectrophotometer. The results showed that mean lipid peroxidation was significantly higher (p&lt;0.05) in malaria positive than malaria negative women, while GSH and ascorbic acid levels were significantly (p&lt;0.05) reduced. The parasite density was significantly reduced in patients who had taken antimalarial drugs relative to those without. While mean ascorbic acid and GSH levels were significantly reduced in those who had taken drugs as compared with those without drugs, the lipid peroxidation level was significantly higher in them. The increase in lipid peroxidation and decrease in GSH and ascorbic acid levels in women who were malaria positive and in those who had taken drugs is indicative of oxidative stress. (Afr. J. Reprod. Health 2010; 14[3]: 209-212).Key words: Pregnant women, malaria, lipid peroxidation, reduced glutathione, Ascorbic aci

The Burden Of Malaria Infection On Pregnant Women And Birth Weight Of Infants In South Western Nigeria

Objective: To determine the effect of malaria infection on pregnant women and the birth weight of the infants in the south western Nigeria.Subject262 pregnant women who came for antenatal clinic at Ade-Oyo maternity hospital. 128 were primigravidae while 134 were multigravidae.Methodology: 2ml of blood was withdrawn from 262 pregnant women who came for antenatal clinic at Ade Oyo maternity hospital. Thick blood smears were prepared for parasite identification and quantification. Anaemia was detected by measuring Hb levels using Drabkin’ssolution. Age, gravidity and history of treatment with antimalaria drugs were obtained from the subjects using questionnaire.Result: The overall prevalence of infection was 41.8%. Primigravidae were more infected (35%) than multigravidae (22%). The prevalencewas significantly higher (

Prevalence of malaria and anaemia in pregnancy in Ibadan, South-western Nigeria

The study investigated the episode of malaria infection and anaemia in pregnancy of 226 women. The overall prevalence of malaria infection among pregnant women was 23.08%, while only 7.1% of non-pregnant women were malaria positive. The mean parasite density was significantly higher in the primigravidae than in the multigravidae (3144±107 versus 1014±158; p0.05). The haemoglobin concentration was significantly higher in malaria positive non-pregnant controls than in the malaria positive primigravidae (11.56±1.01 versus 9.85±1.85

Prevalence of malaria at booking among antenatal clients in a secondary health care facility in Ibadan, Nigeria

The prevalence of malaria parasitemia at booking was studied in 1,848 pregnant women in a secondary hospital in Ibadan, Nigeria. Main outcome variables were patent parasitemia and fever. 8.4% had patent malaria parasitaemia. Most clients (89%) with parasitemia were asymptomatic. Febrile subjects booked at an earlier gestational age [22.7 versus 24.2 weeks] than afebrile patients (p = 0.0052). Anemia was more prevalent among patients with patent parasitemia than those without (58.1% versus 22.6%,