Intervention of standardized ethanol leaf extract of Annickia polycarpa, (DC.) Setten and Maas ex I.M. Turner. (Annonaceae), in Plasmodium berghei infested mice produced anti-malaria action and normalized gross hematological indices.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a global public health burden due to large number of annual infections and casualties caused by its hematological complications. The bark of Annickia polycarpa is an effective anti-malaria agent in African traditional medicine. However, there is no standardization parameters for A. polycarpa. The anti-malaria properties of its leaf are also not known. AIM OF THE STUDY: To standardize the ethanol leaf extract of A. polycarpa (APLE) and investigate its anti-malaria properties and the effect of its treatment on hematological indices in Plasmodium berghei infected mice in the Rane's test. MATERIALS AND METHODS: Malaria was induced by inoculating female ICR mice with 1.0 × 107P. berghei-infected RBCs in 0.2 mL (i.p.) of blood. Treatment was commenced 3 days later with APLE 50, 200, 400 mg/kg p.o., Quinine 30 mg/kg i.m. (Standard drug) or sterile water (Negative control) once daily per group for 4 successive days. Anti-malarial activity and gross malaria indices such as hyperparasitemia, mean change in body weight and mean survival time (MST) were determined for each group. Changes in white blood cells (WBCs), red blood cells (RBCs), platelets (PLT) counts, hemoglobin (HGB) concentration, hematocrit (HCT) and mean corpuscular volume (MCV) were also measured in the healthy mice before infection as baseline and on day 3 and 8 after inoculation using complete blood count. Standardization was achieved by UHPLC-MS chemical fingerprint analysis and quantitative phytochemical tests. RESULTS: APLE, standardized to its total alkaloids, phenolics and saponin contents, produced significant (P < 0.05) dose-dependent clearance of mean hyperparasitemia of 22.78 ± 0.93% with the minimum parasitemia level of 2.01 ± 0.25% achieved at 400 mg/kg p.o. on day 8. Quinine 30 mg/kg i.m. achieved a minimum parasitemia level of 6.15 ± 0.92%. Moreover, APLE (50-400 mg/kg p.o.) evoked very significant anti-malaria activity of 89.22-95.50%. Anti-malaria activity of Quinine 30 mg/kg i.m. was 86.22%. APLE also inverse dose-dependently promotes weight gain with the effect being significant (P < 0.05) at 50 mg/kg p.o. Moreover, APLE dose-dependently increased the MST of malaria infested mice with 100% survival at 400 mg/kg p.o. Quinine 30 mg/kg i.m. also produce 100% survival rate but did not promote (P > 0.05) weight gain. Hematological studies revealed the development of leukocytopenia, erythrocytosis, microcytic anemia and thrombocytopenia in the malaria infected mice which were reverted with the treatment of APLE 50-400 mg/kg p.o. or Quinine 30 mg/kg i.m. but persisted in the negative control. The UHPLC-MS fingerprint analysis of APLE led to identification of one oxoaporphine and two aporphine alkaloids (1-3). Alkaloids 1 and 3 are being reported in this plant for the first time. CONCLUSION: These results indicate that APLE possessed significant anti-malaria, immunomodulatory, erythropoietic and hematinic actions against malaria infection. APLE also has the ability to revoke deleterious physiological alteration produced by malaria and hence, promote clinical cure. These properties of APLE are due to its constituents especially, aporphine and oxoaporphine alkaloids.

Antimalarial activity of the aqueous extract of the latex of Aloe pirottae Berger. (Aloaceae) against Plasmodium berghei in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In spite of worldwide efforts, malaria remains one of the most devastating illnesses in the world. The huge number of lives it takes and the resistance of malaria parasites to current drugs necessitate the search for new effective antimalarial drugs. Medicinal plants have been the major source of such drugs and A. pirottae is one of these plants used traditionally for the treatment of malaria in Ethiopia. AIM: This study was aimed at evaluating the antimalarial activity of the aqueous extract of A. pirottae against chloroquine sensitive P. berghei in mice. MATERIALS AND METHODS: The extract was obtained by macerating the latex of A. pirottae with distilled water. To determine its antiplasmodial activity, a 4-day suppressive model was used by dividing 40 mice into five groups of 8 mice each and given 200, 400 & 600mg/kg of the extract, the standard drug (chloroquine 25mg/kg) and the vehicle (distilled water). Then parasite suppression by the extract, survival time and prevention of loss of body weight, rectal temperature and packed cell volume were assessed. All data were presented as the Mean ±â€¯SEM (Standard Error of the Mean) and analyzed using IBM SPSS version 20. RESULTS: The extract showed moderate antimalarial activity by significantly (p < 0.001) suppressing parasitemia at all dose levels with maximum parasitemia suppression of 47.0% and significantly (p < 0.01) increasing survival time. Furthermore, 400 mg/kg and 600 mg/kg doses showed significant (p < 0.01) prevention of loss in body weight, rectal temperature and packed cell volume. CONCLUSION: Based to the results of this study, A. pirottae is endowed with a moderate antimalarial activity that is in agreement with the traditional claim of A. pirottae, hence may be used as a basis for further studies to be conducted on antimalarial activity of the plant.

Quantification of malaria antigens PfHRP2 and pLDH by quantitative suspension array technology in whole blood, dried blood spot and plasma.

BACKGROUND: Malaria diagnostics by rapid diagnostic test (RDT) relies primarily on the qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and Plasmodium spp lactate dehydrogenase (pLDH). As novel RDTs with increased sensitivity are being developed and implemented as point of care diagnostics, highly sensitive laboratory-based assays are needed for evaluating RDT performance. Here, a quantitative suspension array technology (qSAT) was developed, validated and applied for the simultaneous detection of PfHRP2 and pLDH in a variety of biological samples (whole blood, plasma and dried blood spots) from individuals living in different endemic countries. RESULTS: The qSAT was specific for the target antigens, with analytical ranges of 6.8 to 762.8 pg/ml for PfHRP2 and 78.1 to 17076.6 pg/ml for P. falciparum LDH (Pf-LDH). The assay detected Plasmodium vivax LDH (Pv-LDH) at a lower sensitivity than Pf-LDH (analytical range of 1093.20 to 187288.5 pg/ml). Both PfHRP2 and pLDH levels determined using the qSAT showed to positively correlate with parasite densities determined by quantitative PCR (Spearman r = 0.59 and 0.75, respectively) as well as microscopy (Spearman r = 0.40 and 0.75, respectively), suggesting the assay to be a good predictor of parasite density. CONCLUSION: This immunoassay can be used as a reference test for the detection and quantification of PfHRP2 and pLDH, and could serve for external validation of RDT performance, to determine antigen persistence after parasite clearance, as well as a complementary tool to assess malaria burden in endemic settings.

Effect of a short course of iron polymaltose on acquisition of malarial parasitaemia in anaemic Indonesian schoolchildren: a randomized trial.

BACKGROUND: Concern exists about the safety of iron supplementation given to individuals in malarious areas. The possible unfavourable impact of iron supplementation on malaria might be less when slow-release iron compounds are used instead of ferrous salts, because no toxic non-transferrin bound iron is formed. The aim of this study was to determine the effect of iron supplementation using the slow-release iron compound iron polymaltose (IPM) on the acquisition of malarial parasitaemia. METHODS: A randomized, placebo-controlled trial was performed in schoolchildren aged 5-18 years with mild or moderate anaemia on the Indonesian island Flores. Microscopic malaria-negative children were randomized to receive 8 weeks of IPM (6 mg elemental iron/kg/day) or placebo . The primary outcomes were the occurrence of microscopically detectable malarial parasitaemia at week 4, 8, 12 and 16 after start of treatment and the proportion of participants with real-time (RT) PCR positive malarial parasitaemia at week 16. RESULTS: 294 Children were assigned to the IPM group and 297 to the placebo group. Whereas IPM supplementation failed to increased haemoglobin or ferritin concentrations, the IPM group had a significantly higher rate of occurrence of microscopically detectable parasitaemia [hazard ratio 2.2, 95% C.I. 1.2-4.0; P = 0.01]. This higher rate was confined to iron-replete children. At the end of the study, 89% of the children in the IPM group had remained free from microscopically detectable parasitaemia vs 95% of children in the placebo group. The proportion of plasmodial RT-PCR positive children was similar in both groups at week 16 (IPM group 16.6% vs placebo group 14.3%; P = 0.47). When analysis was restricted to iron-replete children (serum ferritin ≥30 µg/l), there was a trend for a higher proportion being RT-PCR positive at week 16 in the IPM group compared with the placebo group (20 vs 13.3%; P = 0.07). Erythrocyte microcytosis was an independent risk factor for microscopically detectable malarial parasitaemia. CONCLUSIONS: A short course of IPM should be used cautiously in anaemic children in malaria endemic areas, as it has limited efficacy in treating iron deficiency, while it increases the rate of microscopic malarial parasitaemia in those with replete iron stores. Trial registration ISRCTN 83091970. Registered 16 May 2012 (retrospectively registered).

A Neuroprotective Effect of the Glutamate Receptor Antagonist MK801 on Long-Term Cognitive and Behavioral Outcomes Secondary to Experimental Cerebral Malaria.

Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. Due to the substantial social and economic burden of CM, the development of adjuvant therapies is a scientific goal of highest priority. Apart from vascular and immune responses, changes in glutamate system have been reported in CM pathogenesis suggesting a potential therapeutic target. Based on that, we hypothesized that interventions in the glutamatergic system induced by blockage of N-methyl-D-aspartate (NMDA) receptors could attenuate experimental CM long-term cognitive and behavioral outcomes. Before the development of evident CM signs, susceptible mice infected with Plasmodium berghei ANKA (PbA) strain were initiated on treatment with dizocilpine maleate (MK801, 0.5 mg/kg), a noncompetitive NMDA receptor antagonist. On day 5 post-infection, mice were treated orally with a 10-day course chloroquine (CQ, 30 mg/kg). Control mice also received saline, CQ or MK801 + CQ therapy. After 10 days of cessation of CQ treatment, magnetic resonance images (MRI), behavioral and immunological assays were performed. Indeed, MK801 combined with CQ prevented long-term memory impairment and depressive-like behavior following successful PbA infection resolution. In addition, MK801 also modulated the immune system by promoting a balance of TH1/TH2 response and upregulating neurotrophic factors levels in the frontal cortex and hippocampus. Moreover, hippocampus abnormalities observed by MRI were partially prevented by MK801 treatment. Our results indicate that NMDA receptor antagonists can be neuroprotective in CM and could be a valuable adjuvant strategy for the management of the long-term impairment observed in CM.

The Effects of Transdermally Delivered Oleanolic Acid on Malaria Parasites and Blood Glucose Homeostasis in P. berghei-Infected Male Sprague-Dawley Rats.

The present study investigated the effects of transdermally delivered oleanolic acid (OA) monotherapy and in combination with chloroquine (CHQ) on malaria parasites and glucose homeostasis of P. berghei-infected male Sprague-Dawley rats. Oral glucose test (OGT) responses to OA-pectin patch and CHQ-OA combination matrix patch were monitored in non-infected and infected rats. To evaluate the short-term effects of treatment, percentage parasitaemia, blood glucose, glycogen and plasma insulin were monitored in separate groups of animals treated with either OA-patch monotherapy or CHQ-OA combination pectin patch over a 21-days period. Animals treated with drug-free pectin and CHQ acted as untreated and treated positive controls, respectively. Infected control rats exhibited significantly increased parasitaemia which was accompanied by hypoglycaemia. Both OA monotherapy and CHQ-OA combination therapy reduced and cleared the malaria parasites within a period of 4 and 3 days, respectively. Compared to respective controls groups, OGT responses of animals treated with OA monotherapy or CHQ-OA combination therapy exhibited lower blood glucose levels at all time points. A once-off transdermal application of OA-patch or CHQ-OA combination patch significantly improved blood glucose concentrations inducing any changes in insulin concentration. Transdermal OA used as a monotherapy or in combination with CHQ is able to clear and reduce the malaria parasites within a shorter period of time without eliciting any adverse effects on glucose homeostasis of P. berghei-infected rats.

Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

Experimental infection by Trypanosoma evansi in sheep: Occurrence of transplacental transmission and mice infection by parasite present in the colostrum and milk of infected ewes.

The aims of this study were to evaluate vertical transmission of Trypanosoma evansi in sheep experimentally infected, in addition to the mammary transmission by colostrum or milk of these infected sheep to mice. Three pregnant sheep were used: one uninfected, four months pregnant (Sheep A); and two (Sheep B and C) infected intravenously by T. evansi trypomastigotes (4.6×10(6) per animal) on the third (Sheep C) and fourth (Sheep B) month of pregnancy. Both infected sheep developed low and oscillating parasitemia measured by blood smears. Hemogram was performed at seven day intervals, showing anemia, leukocytosis, and lymphocytosis on sheep B and C. Three sheep had twins, where sheep A delivered healthy lambs and both infected sheep had delivered at least one stillborn. Additionally, lambs from sheep B and C died 24 and 72 h post-partum, respectively. Before colostrum intake, four lambs from infected sheep were positives for T. evansi according to blood smear evaluation, serology (CATT/T. evansi), and PCR. Sheep colostrum and milk samples collected from the first four days post-partum were positives for T. evansi on PCR, and these samples were able to infect seven mice (out of 10) orally (n=4/5) and intraperitoneally (n=3/5). Therefore, we conclude that the vertical transmission of T. evansi occurs in pregnant sheep, in addition to a strong possibility of the transmission by colostrum and milk.

Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method.

During their lifespan, circulating RBC are frequently checked for their deformability. This mechanical quality control operates essentially in the human spleen. RBC unable to squeeze though narrow splenic slits are retained and cleared from the blood circulation. Under physiological conditions this prevents microvessels from being clogged by senescent, rigid RBC. Retention of poorly deformable RBC is an important determinant of pathogenesis in malaria and may also impact the clinical benefit of transfusion. Modulating the splenic retention of RBC has already been proposed to support therapeutic approaches in these research fields. To this aim, the development of microplates for high throughput filtration of RBC through microsphere layers (microplate-based microsphiltration) has been undertaken. This review focuses on potential therapeutic applications provided by this technology in malaria chemotherapy and transfusion.

The association between malaria and iron status or supplementation in pregnancy: a systematic review and meta-analysis.

INTRODUCTION: Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI) 0.66-1.20, I(2) = 78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14-2.70 for 1-15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24-0.51, I(2) = 59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. CONCLUSIONS: Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.

Increased serum hepcidin and alterations in blood iron parameters associated with asymptomatic P. falciparum and P. vivax malaria.

BACKGROUND: Asymptomatic Plasmodium spp. infections and anemia are highly prevalent conditions in tropical regions. We studied whether asymptomatic parasitemia induces hepcidin- and/or cytokine-mediated iron maldistribution and anemia. DESIGN AND METHODS: A group of 1197 Indonesian schoolchildren, aged 5-15 years, were screened by microscopy for the presence of parasitemia. Concentrations of hemoglobin, serum hepcidin and parameters of iron status and inflammation were determined at baseline and 4 weeks after antimalarial treatment. RESULTS: Asymptomatic P. falciparum and P. vivax parasitemia were detected in 73 (6.1%) and 18 (1.5%) children, respectively, of whom 84% and 83% had a C-reactive protein concentration below 5 mg/L. Children with P. falciparum or P. vivax parasitemia had significantly lower hemoglobin concentrations than 17 aparasitemic controls (12.6 and 12.2 g/dL versus 14.4 g/dL; P<0.01), together with significantly higher serum hepcidin concentrations (5.2 and 5.6 nM versus 3.1 nM; P<0.05). The latter was associated with signs of iron maldistribution with higher ferritin concentrations and lower values of serum iron concentration, transferrin saturation and erythrocyte mean cell volume. Concentrations of growth differentiation factor 15 were similar across groups. Antimalarial treatment partly reversed these abnormalities and led to a significant increase in hemoglobin concentration. CONCLUSIONS: Asymptomatic malarial parasitemia is associated with increased hepcidin concentrations and anemia, in the absence of a manifest acute phase response. Prolonged iron maldistribution may be an underestimated cause of anemia. Screening for parasitemia should be performed before starting iron supplementation, as iron therapy may be less effective and even hazardous in these circumstances.

Inhibitory effects of (-)-epigallocatechin-3-gallate from green tea on the growth of Babesia parasites.

(-)-Epigallocatechin-3-gallate (EGCG) is the major tea catechin and accounts for 50-80% of the total catechin in green tea. (-)-Epigallocatechin-3-gallate has antioxidant, anti-inflammatory, anti-microbial, anti-cancer, and anti-trypanocidal activities. This report describes the inhibitory effect of (-)-Epigallocatechin-3-gallate on the in vitro growth of bovine Babesia parasites and the in vivo growth of the mouse-adapted rodent babesia B. microti. The in vitro growth of the Babesia species was significantly (P<0.05) inhibited in the presence of micromolar concentrations of EGCG (IC50 values=18 and 25 microM for B. bovis, and B. bigemina, respectively). The parasites showed no re-growth at 25 microM for B. bovis and B. bigemina in the subsequent viability test. The drug significantly (P<0.05) inhibited the growth of B. microti at doses of 5 and 10 mg/kg body weight, and the parasites completely cleared on day 14 and 16 post-inoculation in the 5 and 10 mg/kg treated groups, respectively. These findings highlight the potentiality of (-)-Epigallocatechin-3-gallate as a chemotherapeutic drug for the treatment of babesiosis.

Low red cell production may protect against severe anemia during a malaria infection--insights from modeling.

The malaria parasite causes lysis of red blood cells, resulting in anemia, a major cause of mortality and morbidity. Intuitively, one would expect the production of red blood cells to increase in order to compensate for this loss. However, it has been observed that this response is weaker than would be expected. Furthermore, iron supplementation for iron deficient children in malaria endemic regions can paradoxically adversely affect the clinical outcome of malaria infection. A possible explanation may lie in the preference that some malaria parasites show for infecting immature red blood cells (reticulocytes). In the presence of a parasite preference for immature red cells, a rise in red cell production can 'fuel the fire' of infection by increasing the availability of the parasite's preferred target cell. We present a mathematical model of red blood cell production and infection in order to explore this hypothesis. We assess the effect of varying the reticulocyte replacement rate and preference of the parasite for reticulocytes on four key outcome measures assessing anemia and parasitemia. For a given level of parasite preference for reticulocytes we uncover an optimal erythropoietic response which minimizes disease severity. Increasing red blood cell production much above this optimum confers no benefit to the patient, and in fact can increase the degree of anemia and parasitemia. These conclusions are consistent with epidemiological studies demonstrating that both iron deficiency and anemia are protective against severe malaria, whilst iron supplementation in malaria endemic regions is with an increased number of malaria related adverse effects. Thus, suppression of red blood cell production, rather than being an unfortunate side effect of inflammation, may be a host protective effect against severe malarial anemia.

Antiplasmodial activity of root extract and fractions of Croton zambesicus.

AIM OF THE STUDY: Antiplasmodial activity of root extract and fractions of Croton zambesicus were evaluated to ascertain the folkloric claim of its antimalarial activity and elucidate its antiplasmodial mechanism of action. MATERIAL AND METHOD: The crude ethanolic root extract (27-81 mg/kg) and gradient fractions (n- hexane, chloroform, ethyl acetate and methanol; 54 mg/kg) of Croton zambesicus were investigated for antiplasmodial activity against chloroquine--sensitive Plasmodium berghei infections in mice. The antiplasmodial activity during early and established infections as well as the prophylactic activity were investigated. Chloroquine (5 mg/kg) and pyrimethamine (1.2 mg/kg) were used as positive controls. Thin films made from tail blood of each mouse were used to assess the level of parasitaemia of the mice. Oxidant generation potentials of the crude extract and fractions was also evaluated to elucidate their mechanism of action. RESULTS: The crude root extract (27-81 mg/kg) demonstrated significant (P<0.01-0.001) schizonticidal activity during early and established infections and also had prophylactic activity. The activity was comparable to that of the standard drug used (chloroquine 5 mg/kg, pyrimethamine 1.2 mg/kg). Methanol, ethyl acetate and chloroform fractions had comparative in vivo antiplasmodial activity and oxidant generation potentials. CONCLUSION: The antiplasmodial activity of this root extract and fractions which is likely to be through peroxidation confirms the folkloric use of this plant.

Iron incorporation and post-malaria anaemia.

BACKGROUND: Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the magnitude and duration of these effects are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We examined the red blood cell incorporation of oral administered stable isotopes of iron and compared incorporation between age matched 18 to 36 months old children with either anaemia post-malaria (n = 37) or presumed iron deficiency anaemia alone (n = 36). All children were supplemented for 30 days with 2 mg/kg elemental iron as liquid iron sulphate and administered (57)Fe and (58)Fe on days 1 and 15 of supplementation respectively. (57)Fe and(58)Fe incorporation were significantly reduced (8% vs. 28%: p<0.001 and 14% vs. 26%: p = 0.045) in the malaria vs. non-malaria groups. There was a significantly greater haemoglobin response in the malaria group at both day 15 (p = 0.001) and 30 (p<0.000) with a regression analysis estimated greater change in haemoglobin of 7.2 g/l (s.e. 2.0) and 10.1 g/l (s.e. 2.5) respectively. CONCLUSION/SIGNIFICANCE: Post-malaria anaemia is associated with a better haemoglobin recovery despite a significant depressant effect on oral iron incorporation which may indicate that early erythropoetic iron need is met by iron recycling rather than oral iron. Supplemental iron administration is of questionable utility within 2 weeks of clinical malaria in children with mild or moderate anaemia.

In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum.

Nowadays, chloroquine-resistant malaria appears in almost all endemic regions. Ferroquine is a derivative of chloroquine and shows good activity in vitro and in animal models, but the development of cross-resistance is of concern. We tested in vitro susceptibilities of Plasmodium falciparum field isolates from Gabon to ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was present in all parasite isolates (median 50% inhibitory concentration = 113 nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly active, and no significant correlation between any of the three drugs was observed. In contrast to our findings, previous studies showed an association between chloroquine and ferroquine activities. We could reproduce this association by using different initial parasitemias, but analysis of covariance revealed that initial parasitemia and not parasite strain was the critical determinant for the correlation between chloroquine and ferroquine activities. We conclude that ferroquine is highly active in chloroquine-resistant parasites, and we anticipate no enhanced selection for resistance against ferroquine in chloroquine-resistant parasites.

Curcumin-artemisinin combination therapy for malaria.

Artemisinin and curcumin show an additive interaction in killing Plasmodium falciparum in culture. In vivo, 3 oral doses of curcumin following a single injection of alpha,beta-arteether to Plasmodium berghei-infected mice are able to prevent recrudescence due to alpha,beta-arteether monotherapy and ensure almost 100% survival of the animals.

Emergence and clearance of gametocytes in uncomplicated Plasmodium falciparum malaria.

We reviewed the records of 1,175 patients with uncomplicated Plasmodium falciparum malaria to determine the prevalence of gametocytemia. All patients were admitted and received artemisinin combination therapy. Blood films were checked daily until discharge. Circulating gametocytes were observed in 240 (20.2%) of patients and in most cases (222 of 240, 92.5%) gametocytemia was detected during the first 24 hours after admission. Gametocytes were first seen in 174 cases on admission, in 24 cases at 12 hours, and in 24 cases at 24 hours. The longest interval between admission and first appearance of gametocytes was 192 hours. The median gametocyte clearance time was 163 hours (range = 12-806) in the 219 patients in whom gametocytemia resolved. However, 21 patients (9.8%) still had gametocytemia on discharge. Gametocytemia generally is present within the first 24 hours after admission, and emerges in only 1.9% of patients later on during treatment with artemisinin.

Curcumin for malaria therapy.

Malaria remains a major global health concern. New, inexpensive, and effective antimalarial agents are urgently needed. Here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant Plasmodium falciparum growth in culture in a dose dependent manner with an IC(50) of approximately 5 microM. Additionally, oral administration of curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces blood parasitemia by 80-90% and enhances their survival significantly. Thus, curcumin may represent a novel treatment for malarial infection.

Biochemical profiles in Friesian cattle naturally infected with Theileria annulata in Saudi Arabia.

The biochemical parameters were studied in adult and young Friesian cattle naturally infected with Theileria annulatta in the Qassim Region, Saudi Arabia. Forty-three clinical cases of tropical theileriosis were studied, together with 40 clinically healthy Friesian cattle. Cattle clinically infected with T. annulata had significantly lower serum total protein, albumin, globulin, creatinine, calcium, phosphorus, magnesium, potassium, iron and copper concentrations and significantly higher AST activity and bilirubin concentration than the healthy cattle.