Potential toxicity of Chlorpheniramine plus chloroquine for the treatment of childhood malaria

Objectives: To compare the adverse effects of two regimens of chlorpheniramine plus chloroquine (CP+CQ) in childrenwho live in a countrywhere chloroquine resistantmalaria is endemic. Methods: 99 children with acute uncomplicated malaria were randomised into two treatment groups. Group I received high dose chlorpheniramine (6mg +12mg/day for 7days in children = 5years; 8mg + 18mg/day for 7days in those >5years) plus chloroquine 10mg/kg daily for 3 days. Group II received a 50% higher dose of chlorpheniramine plus chloroquine 10mg/kg daily for 3 days. Outcome measures were vital signs, clinical response and parasite clearance on days 0-7 and day 14. Results: Parasite clearance, fever clearance and cure rate were comparable for the two groups. Drowsiness occurred in 66.7% of high dose and 86.3% of higher dose CP+CQ subjects (p = 0.05). Compared to children treated with high dose, those treated with higher dose CP+CQhad significantly lower respiratory rates on day 2 (p = 0.001), day 6 (p = 0.015), and on day 14 (p = 0.003). Conclusion: The higher rates of drowsiness and lower respiratory rates in children treated with higher dose CP+CQ calls for caution in the clinical application of the higher dose combination. The higher dose has no additional benefit andmay in fact be dangerous.Keywords: Chloroquine resistant malaria, chlorpheniramine-chloroquine, treatment, adverse effects, drowsiness, respiratory depressio

Effet des médicaments antipaludiques et l'infection causée par le paludisme sur le stress oxydatif chez les femmes enceintes.

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<0.05) in malaria positive than malaria negative women, while GSH and ascorbic acid levels were significantly (p<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.Cette étude a examiné l&apos;effet de l&apos;infection causée par le paludisme et des médicaments antipaludiques sur le stress oxydatif chez 250 femmes enceintes et non enceintes à l&apos;hôpital Adeoyo à Ibadan, Nigéria. Le stress oxydatif a été déterminé en mesurant la peroxydation du lipide sérique, l&apos;acide ascorbique et les niveaux réduits du glutathion (GSH) à l&apos;aide d&apos;un spectrophotomètre. Les résultats ont montré que la peroxydation lipide moyen a été élevée de manière significative (p<0,05) chez les femmes dont l&apos;analyse pour déterminer la présence du paludisme a été positive par rapport à celles dont l&apos;analyse a été négative, alors que les niveaux du GSH et l&apos;acide ascorbique ont été réduits de manière significative (p<0,05). La densité parasitaire a été réduite de manière significative chez les patientes qui avaient pris des médicaments antipaludiques par rapport à celles qui n&apos;en avaient pas pris. Alors que les niveaux de l&apos;acide ascorbique et du GSH ont été réduits de manière significative par rapport à celles qui n&apos;avaient pas pris des médicaments, le niveau de la peroxydation a été beaucoup plus élevé chez elles. L&apos;augmentation dans la peroxydation lipide et la réduction dans le GSH et dans les niveaux de l&apos;acide ascorbique chez les femmes dont l&apos;analyse du paludisme a été positive et chez celles qui avaient pris des médicaments est une indication du stress oxydati

Sulphadoxine-pyrimethamine alters the antioxidant defense system in blood of rabbit

Summary: Sulphadoxine-pyrimethamine (SP) despite reported resistance remains an important drug of choice for the treatment and control of malaria in most endemic areas. Exacerbation of intra-erythrocytic oxidative stress might contribute to the process of elimination of malaria parasites in the body. The effect of treatment with SP on the antioxidant defense system was investigated using rabbit as a model. Ten male rabbits were divided into two groups of five animals each. The first group was administered with normal saline and served as control. The second group received a single dose of SP (26.25mg/kg body weight). Blood samples were collected before and at 6, 12 and 24 h after drug administration. Activity of cellular enzymatic antioxidants, superoxide dismutase (SOD) and catalase (CAT), and level of reduced glutathione (GSH) were assayed using standard spectrophotometric methods. Serum lipid peroxidation was assessed by the formation of thiobarbituric acid reactive species (TBARS) while protein content was assayed by the method of Lowry et al., 1951. SOD activity was observed to increase progressively by 4.9, 63.4 and 120.8% at 6, 12 and 24 h respectively, after drug administration. Similarly, CAT activity increased by 44.5, 82.6 and 116.3% at 6, 12 and 24 h, respectively. TBARS level also increased significantly by 45.5, 118.2 and 186.4%, respectively. However, the level of GSH decreased by 41.9% at 6 h and remained so up till the 12 h, but by 24 h after drug administration, the level of the thiol substance has increased considerably up to 48.4% above the baseline level. SP treatment altered the antioxidant defense system in blood and may therefore induce oxidative stress by generating reactive oxygen species. This might play significant role in the therapeutic and adverse effects associated with the drug

Antimalarial and toxicological effects of aqueous leaf extract of Lawsonia inermis Lythraceae (Linn) alone and in combination with Alstonia boonei on Plasmodium berghei- infected mice

Background: Lawsonia inermis Lythraceae (Linn) and Alstonia boonei De wild are well known for their antimalarial potentials in traditional medicine. However, there is no scientific evidence for this claim.Objective: The aim was to evaluate the in vivo antimalarial and toxicological effects of the aqueous extracts of Lawsonia inermis alone and in combination with Alstonia boonei in Plasmodium berghei infected miceMethod: Fifty four mice were divided into 9 groups of 6 mice each. Groups 1 – 3 were healthy control, P. berghei infected and P. berghei infected mice treated with Chloroquine dose (positive control), respectively. Groups 4 – 6 were P. berghei infected mice orally administered 50, 100, and 200 mg/kg of Lawsonia inermis while groups 7 – 9 were also P. berghei infected mice but received 50, 100, and 200 mg/kg of Lawsonia inermis and Alstonia boonei extracts. All infected mice were inoculated with malaria parasites on the first day and extracts administrationcommenced on the fourth day and lasted for 7 days. The mice were sacrificed on the 14th day post-inoculation and the activities of liver, kidney and serum enzymes were analyzed.Results: The treatment of parasitized mice with Lawsonia inermis at 100 and 200 mg/kg body weight showed the most significant (p&lt;0.05) antimalarial activity against P. berghei infection. A combined treatment with Lawsonia inermis and Alstonia boonei suppressed malarial infection significantly (p&lt;0.05) at 50 mg/kg and increased packed cell volume (PCV). Administration of 100 mg/kg L. inermis significantly (p&lt;0.05) elevated the activities of alanine amino transaminase (ALT) and aspartate amino transaminase (AST) in the liver and kidneys but not in theserum. Also, alkaline phosphatase (ALP) activity was increased in the liver, kidneys and serum by 100 mg/kg Lawsonia inermis alone.Conclusion: Findings revealed the chemosuppressive potential of Lawsonia inermis against P. berghei as well as its toxicity to the liver and kidney.Keywords:  Lawsonia inermis, Alstonia boonei, Plasmodium berghei, Parasitemia, Amino transferase

Prévalence du paludisme au moment de l&apos;inscription chez les clients pour le service prénatal auprès d&apos;un Centre de santé secondaire à 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%, p<0.0001). Malaria parasitaemia was higher among nulliparous women than other parity groups (p<0.0001). Symptomatic malaria was associated with early booking for antenatal care and malaria parasitemia was a significant determinant of anemia. The prevalence of malaria parasitaemia in this study is much lower than in previous reports.L&apos; étude sur la prévalence de la parasitémie du paludisme au moment de l&apos;inscription a été menée auprès des 1,848 femmes enceintes dans un hôpital secondaire à Ibadan, Nigéria. Les principaux variables de résultat étaient la parasitémie évidente et la fièvre. 8.4 % (155/1848) avaient la parasitémie du paludisme évidente. La plupart des sujets (89%) qui avaient la parasitémie étaient asymptomatiques. Les sujets fébriles se sont inscrites à un âge gestationnel plus jeune [22,7 semaines par opposition à 24,2 semaines] que les patientes afébriles (p=0,0052). L&apos;anémie était plus significativement prévalente chez les patientes qui avaient la parasitémie évidente (58, 1%) par rapport à des patientes qui n&apos;en avaient pas (58,1% contre, 22,6%, p<0,0001). Les femmes nullipares avaient une incidence plus élevée de la parasitémie du paludisme par rapport aux autres groupes de parité (p<0001). La prévalence du paludisme dans cette étude est beaucoup inférieure par rapport aux résultats signalés dans le passé. Le paludisme symptomatique a été lié à l&apos;inscription précoce pour le service prénatal et la parasitémie du paludisme était un déterminant important de l&apos;anémie

Anti-protozoan activities of Harungana madagascariensis stem bark extract on trichomonas and malaria

AIM OF THE STUDY: The ethanolic stem bark extract of Harungana madagascariensis (Hypericaceae), (Choisy) Poir were evaluated for their activities on Trichomonas gallinae (Rivolta) Stabler isolated from the pigeon (Columba livia). It was also tested for their anti-malarial activity on N67 Plasmodium yoelii nigeriensis (in vivo) in mice and on Plasmodium falciparum isolates in vitro. MATERIALS AND METHODS: The anti-trichomonal screening was performed in vitro using Trichomonas gallinae culture. The minimum lethal concentration (MLC) is the lowest concentration of the test extract in which no motile organisms were observed. The anti-malarial effects were determined in-vivo for suppressive, curative and prophylactic activities in mice receiving a standard inoculum size of 1 × 107 (0.2 ml) infected erythrocytes of Plasmodium yoelii nigeriensis intraperitoneally, and the in vitro was performed against 3 isolates of Plasmodium falciparum in a candle jar procedures. RESULTS: The IC50 of the extract and metronidazole (MDZ) (Flagyl) on Trichomonas gallinae at 48 h are 187 and 1.56 μg/ml. The IC50 of the extract, chloroquine (CQ) and artemether (ART) on Plasmodium falciparum are between 0.052 and 0.517 μg/ml for the extract and 0.021 and 0.0412 μg/ml for ART and CQ, respectively. The actions of the extract in in vivo study on Plasmodium yoelii nigeriensis showed that in both suppressive and prophylactic tests the percentages chemo-suppressive were between 28.6–44.8% and 30.2–78.2% respectively, while only 80 mg/kg of the extract reduced the parasitaemia level when compared to the control and the standard drugs in curative test. CONCLUSIONS: Harungana madagascariensis stem bark extract therefore exhibited significant anti-protozoan effects against Trichomonas and Plasmodium both in vivo and in vitro