In vivo antiplasmodial activities and acute toxicity assessment of two plant cocktail extracts commonly used among Southwestern Nigerians.

Discovering and developing the desired antimalarials continue to be a necessity especially due to treatment failures, drug resistance, limited availability and affordability of antimalarial drugs and costs especially in poor malarial endemic countries. This study investigated the efficacies of two plant cocktails; CtA and CtB, selected based on their traditional usage. Efficacies of the cocktail extracts, chloroquine and pyrimethamine against Plasmodium berghei berghei were evaluated in mice using the suppressive, curative and prophylactic test models, after oral and intraperitoneal acute toxicity determination of the plant cocktails in accordance with Lorke's method. Data was analyzed using SPSS software version 23.0 with level of significance set at P < 0.05. The median lethal dose was determined to be higher than 5000 mg/kg body weight orally for both CtA and CtB; and 316.23 mg/kg body weight intraperitoneally for CtA. Each cocktail exhibited high dose dependent Plasmodium berghei berghei inhibition which was 96.95% and 99.13% in the CtA800 mg/kg and CtB800 mg/kg doses in the curative groups respectively, 96.46% and 78.62% for CtA800mg/kg and CtB800mg/kg doses in the suppressive groups respectively, as well as 65.05% and 88.80% for CtA800mg/kg and CtB800mg/kg doses in the prophylactic groups respectively. Throughout the observation periods, the standard drugs, chloroquine phosphate and pyrimethamine maintained higher inhibitions up to 100%. These findings demonstrate that CtA and CtB possess good antimalarial abilities and calls for their development and standardization as effective and readily available antimalarial options. The acute toxicity results obtained underscore the importance of obtaining information on toxicities of medicinal plant remedies before their administration in both humans and animals.

Transfusional malaria in the neonatal period in Lagos, South-West Nigeria.

BACKGROUND AND OBJECTIVES: Sick neonates in malaria endemic areas are frequently transfused with donor blood unscreened for malaria parasite. Consequently, they are at risk of transfusional malaria which can lead to increased neonatal mortality. The study aimed to determine the burden of transfusional malaria in neonates to help in policy formulation on prevention of transfusional malaria. MATERIALS AND METHODS: One hundred and sixty four neonates admitted into the neonatal unit of a tertiary hospital over a 10 month period who were scheduled for blood transfusion were screened for malaria parasites pre-transfusion, at three and 14 days post transfusion using Giemsa stained thick and thin films. Donor blood was screened for malaria parasites at the point of transfusion. Neonates who developed malaria parasitaemia post transfusion were followed up for signs of malaria. RESULTS: All recruited neonates tested negative to malaria parasite pre- transfusion. One hundred and twenty (73.2%) were term neonates with 94(57.3%) aged 1-7days. Four (2.4%) neonates developed malaria parasitaemia three days post transfusion and all four developed fever that resolved on treatment for malaria. Three (1.8%) of 164 donor blood samples had malaria parasitaemia and all three (100%) neonates who were transfused with the infected donor blood developed malaria parasitaemia post transfusion. However, one neonate who developed malaria parasitaemia post transfusion was transfused with non-infected donor blood. CONCLUSIONS: The prevalence of transfusional malaria in this study is low (2.4%). However, 100% of neonates who received malaria infected donor blood developed transfusional malaria. We therefore recommend routine screening of donor pre-transfusion, testing of neonates who develop fever post transfusion and treatment of those who test positive to malaria.

Assessment of Markers of Antimalarial Drug Resistance in Plasmodium falciparum Isolates from Pregnant Women in Lagos, Nigeria.

BACKGROUND: The use of antimalarial drugs for prevention and treatment is a major strategy in the prevention of malaria in pregnancy. Although sulphadoxine-pyrimethamine (SP) is currently recommended for intermittent preventive treatment of malaria during pregnancy in Nigeria, previously used drugs for prophylaxis such as chloroquine (CQ) and pyrimethamine are accessible as they are purchased over the counter. This study describes the markers of absence or presence of resistance to quinoline (Pfcrt and Pfmdr 1) and type 1 antifolate antimalarial medicines (Pfdhfr). METHODS: Plasmodium falciparum-positive dried blood spots from pregnant women attending antenatal clinics for the first time during current pregnancy were investigated for the presence of mutations at codons 72-76 of Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene by real time polymerase chain reaction (PCR) using haplotype-specific probes. PCR followed by sequence analysis was used to identify mutations at codons 86, 184, 1034, 1042 and 1246 of P. falciparum multi-drug resistance-1 (Pfmdr1) gene; and codons 16, 50, 51, 59, 108, 140 and 164 of Pfdhfr gene. RESULTS: Two haplotypes of Pfcrt (n = 54) were observed: CVMNK 13(24.2%) and CVIET 41 (75.9%) of the samples. The SVMNT haplotype was absent in this population. The Pfmdr1 (n = 28) haplotypes were NYSND 15(53.6%), YYSND 5(17.9%), NFSND 6(21.4%) and YFSND 2(7.1%). The Pfdhfr (n = 15) were ACNCSVI 4(26.7%), and ACICNSVI 1(6.7%) and ACIRNVI 10 (66.7%). The rate of occurrence of Pfcrt 76T, Pfdhfr108N, Pfmdr186Y and 184F were 75.9%, 73.3%, 25% and 28.1% respectively. The Pfmdr1 86Y was associated with low parasitaemia (median = 71 parasites/µl, P = 0.024) while Pfcrt 76T was associated with young maternal age (mean 24.1 ± 4.5 years; P = 0.006). The median parasitaemia were similar (P>0.05) in wild and mutant strains of Pfcrt 76, Pfmdr1 184 and Pfdhfr 108. There was no association between gravidity or gestational age of the women and presence of mutations in the Pfcrt, Pfmdr1 or Pfdhfr genes (P>0.05). CONCLUSION: Markers of resistance to chloroquine and pyrimethamine were high, whereas cycloguanil-resistance marker was not present in the studied population. The low level of mutations in the Pfmdr1gene indicates likely efficacy of amodiaquine against malaria in pregnancy.

Scaling up of intermittent preventive treatment of malaria in pregnancy using sulphadoxine-pyrimethamine: prospects and challenges.

Intermittent preventive treatment of malaria during pregnancy with sulphadoxine-pyrimethamine (IPTpSP) is one of the major strategies of malaria control in most African countries where malaria is endemic. The use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy was adopted when proof of its superiority to weekly prophylactic dosing with either chloroquine or pyrimethamine became evident from studies in different malaria endemic countries. The administration of 2 and 3 treatment doses of SP for HIV-negative and HIV-positive pregnant women respectively, given after quickening and at an interval not less than 4 weeks was recommended. The prospects of this control strategy lies on the efficacy of SP, convenient treatment dose and high compliance rate. However, the implementation of this strategy and the efficacy of SP are faced with challenges such as: timing of SP administration, rising levels of parasite resistance to SP in the general population, effect of folate supplementation, adequacy of the recommended doses with regards to malaria endemicity and HIV status, interactions between SP and antiretroviral drugs and low coverage in the bid to scale-up its use. This review highlights the prospects and challenges of scaling up IPTp-SP.