Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial.

INTRODUCTION: Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. METHODS AND ANALYSIS: A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. ETHICS AND DISSEMINATION: This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. TRIAL REGISTRATION NUMBER: PACTR202011812241529.

Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso.

In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.

Correction: Performance of PfHRP2­RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso.

[This corrects the article DOI: 10.1007/s12639-023-01566-x.].

Performance of PfHRP2-RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso.

In this study, we evaluated the performance of a P. falciparum Histidine Rich Protein 2 (PfHRP2)-based rapid diagnostic test (RDT) used for malaria case detection (SD-Bioline malaria RDT P.f®) along with light microscopy (LM) against qPCR among children during the first year of life in a high and seasonal malaria transmission area in Burkina Faso. A total of 723 suspected malaria cases (including multiple episodes) that occurred among 414 children participating in a birth-cohort study were included in the present analysis. Factors including age at the time of malaria screening, transmission season and parasite densities were investigated for their potential influence in the performance of the RDT. Clinical malaria cases as detected by RDT, LM and qPCR were 63.8%, 41.5% and 49.8%, respectively. Compared with qPCR, RDT had a false-positive results rate of 26.7%, resulting in an overall accuracy of 79.9% with a sensitivity of 93%, a specificity of 66.1%, a Positive Predictive Value of 73.3% and a Negative Predictive Value of 91.6%. Its specificity differed significantly between high and low transmission seasons (53.7% vs 79.8%; P < 0.001) and decreased with increasing age (80.6-62%; P for trend = 0.024). The overall accuracy of LM was 91.1% and its performance was not significantly influenced by transmission season or age. These findings highlight the need to adapt malaria diagnostic tools recommendations to face the challenge of adequate malaria detection in this population group living in high burden and seasonal malaria transmission settings.

Household costs associated with seeking malaria treatment during pregnancy: evidence from Burkina Faso and The Gambia.

BACKGROUND: Malaria in pregnancy remains a major health threat in sub-Saharan Africa to both expectant mothers and their unborn children. To date, there have been very few studies focused on the out of pocket costs associated with seeking treatment for malaria during pregnancy. METHODS: A cross-sectional survey was undertaken in Burkina Faso and The Gambia to estimate the direct and indirect costs associated with outpatient consultations (OP) and inpatient admissions (IP). Direct costs were broken down into medical (admission fees, drug charges, and laboratory fees), and non-medical (transportation and food). Indirect costs reflected time lost due to illness. In total, 220 pregnant women in Burkina Faso and 263 in The Gambia were interviewed about their treatment seeking decisions, expenditure, time use and financial support associated with each malaria episode. RESULTS: In Burkina Faso 6.7% sought treatment elsewhere before their OP visits, and 27.1% before their IP visits. This compares to 1.3% for OP and 25.92% for IP in The Gambia. Once at the facility, the average direct costs (out of pocket) were 3.91US$ for an OP visit and 15.38US$ of an IP visit in Burkina Faso, and 0.80US$ for an OP visit and 9.19US$ for an IP visit in The Gambia. Inpatient direct costs were driven by drug costs (9.27US$) and transportation costs (2.72US$) in Burkina Faso and drug costs (3.44 US$) and food costs (3.44 US$) in The Gambia. Indirect costs of IP visits, valued as the opportunity cost of time lost due to the illness, were estimated at 11.85US$ in Burkina Faso and 4.07US$ in The Gambia. The difference across the two countries was mainly due to the longer time of hospitalization in Burkina Faso compared to The Gambia. In The Gambia, the vast majority of pregnant women reported receiving financial support from family members living abroad, most commonly siblings (65%). CONCLUSIONS: High malaria treatment costs are incurred by pregnant women in Burkina Faso and The Gambia. Beyond the medical costs of fees and drugs, costs in terms of transport, food and time are significant drivers. The role of remittances, particularly their effect on accessing health care, needs further investigation.

Prevalence and factors associated with carriage of Pfmdr1 polymorphisms among pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and artemether-lumefantrine for malaria treatment in Burkina Faso.

BACKGROUND: Single nucleotide polymorphisms occurring in the Plasmodium falciparum multidrug resistant gene 1 (pfmdr1) are known to be associated with aminoquinoline resistance and, therefore, represent key P. falciparum markers for monitoring resistance both in susceptible groups (children under 5 years old and pregnant women) and in the general population. This study aimed to determine prevalence and factors associated with the carriage of pfmdr1 N86Y, Y184F and D1246Y polymorphisms among pregnant women in a setting of high malaria transmission in Burkina Faso. METHODS: Plasmodium falciparum isolates were collected at the first antenatal care visit (ANC-1) as well as at delivery from pregnant women participating in the COSMIC trial (NTC01941264), which assessed malaria preventive interventions during pregnancy in the Nanoro Health District. Here, pregnant women received intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and malaria infections and/or diseases were treated using artemether-lumefantrine (AL) during the trial. Parasite DNA was extracted from dried blood spots and the presence of pfmdr1 mutations at positions 86, 184 and 1246 was determined using nested PCR, followed by restriction fragment length polymorphism (RFLP) analysis. RESULTS: A prevalence of 13.2% (20/151) and 12.1% (14/116) of the pfmdr1 86Y mutant allele was found at ANC-1 and at delivery, respectively, while no mutant allele was observed for Y184F and D1246Y codons at both ANC-1 and at delivery. There were no significant factors associated with pfmdr1 86Y mutant allele carriage at ANC-1. However, malaria infections at delivery with a parasite density above the median (2237.2 (IQR: 613.5-11,425.7) parasites/µl) was associated with an increase risk of pfmdr1 86Y mutant allele carriage (AOR = 5.5 (95% CI 1.07-28.0); P = 0.04). In contrast, both three or more IPTp-SP doses (AOR = 0.25 (95% CI 0.07-0.92); P = 0.04) and one or more AL treatment (AOR = 0.25 (95% CI 0.07-0.89); P = 0.03) during pregnancy were associated with a significant reduce risk of pfmdr1 86Y mutant allele carriage at delivery. CONCLUSION: These findings suggest that both high coverage of IPTp-SP and the use of AL for the treatment of malaria infection/disease during pregnancy select for pfmdr1 N86 wild-type allele at delivery.

Artemisinin-based combination therapy during pregnancy: outcome of pregnancy and infant mortality: a cohort study.

BACKGROUND: The World Health Organization (WHO) recommendation of treating uncomplicated malaria during the second and third trimester of pregnancy with an artemisinin-based combination therapy (ACT) has already been implemented by all sub-Saharan African countries. However, there is limited knowledge on the effect of ACT on pregnancy outcomes, and on newborn and infant's health. METHODS: Pregnant women with malaria in four countries (Burkina Faso, Ghana, Malawi and Zambia) were treated with either artemether-lumefantrine (AL), amodiaquine-artesunate (ASAQ), mefloquine-artesunate (MQAS), or dihydroartemisinin-piperaquine (DHA-PQ); 3127 live new-borns (822 in the AL, 775 in the ASAQ, 765 in the MQAS and 765 in the DHAPQ arms) were followed-up until their first birthday. RESULTS: Prevalence of placental malaria and low birth weight were 28.0% (738/2646) and 16.0% (480/2999), respectively, with no significant differences between treatment arms. No differences in congenital malformations (p = 0.35), perinatal mortality (p = 0.77), neonatal mortality (p = 0.21), and infant mortality (p = 0.96) were found. CONCLUSIONS: Outcome of pregnancy and infant survival were similar between treatment arms indicating that any of the four artemisinin-based combinations could be safely used during the second and third trimester of pregnancy without any adverse effect on the baby. Nevertheless, smaller safety differences between artemisinin-based combinations cannot be excluded; country-wide post-marketing surveillance would be very helpful to confirm such findings. Trial registration ClinicalTrials.gov, NCT00852423, Registered on 27 February 2009, https://clinicaltrials.gov/ct2/show/NCT00852423.

The assessment of gestational age: a comparison of different methods from a malaria pregnancy cohort in sub-Saharan Africa.

BACKGROUND: Determining gestational age in resource-poor settings is challenging because of limited availability of ultrasound technology and late first presentation to antenatal clinic. Last menstrual period (LMP), symphysio-pubis fundal height (SFH) and Ballard Score (BS) at delivery are therefore often used. We assessed the accuracy of LMP, SFH, and BS to estimate gestational age at delivery and preterm birth compared to ultrasound (US) using a large dataset derived from a randomized controlled trial in pregnant malaria patients in four African countries. METHODS: Mean and median gestational age for US, LMP, SFH and BS were calculated for the entire study population and stratified by country. Correlation coefficients were calculated using Pearson's rho, and Bland Altman plots were used to calculate mean differences in findings with 95% limit of agreements. Sensitivity, specificity, positive predictive value and negative predictive value were calculated considering US as reference method to identify term and preterm babies. RESULTS: A total of 1630 women with P. falciparum infection and a gestational age > 24 weeks determined by ultrasound at enrolment were included in the analysis. The mean gestational age at delivery using US was 38.7 weeks (95%CI: 38.6-38.8), by LMP, 38.4 weeks (95%CI: 38.0-38.9), by SFH, 38.3 weeks (95%CI: 38.2-38.5), and by BS 38.0 weeks (95%CI: 37.9-38.1) (p < 0.001). Correlation between US and any of the other three methods was poor to moderate. Sensitivity and specificity to determine prematurity were 0.63 (95%CI 0.50-0.75) and 0.72 (95%CI, 0.66-0.76) for LMP, 0.80 (95%CI 0.74-0.85) and 0.74 (95%CI 0.72-0.76) for SFH and 0.42 (95%CI 0.35-0.49) and 0.77 (95%CI 0.74-0.79) for BS. CONCLUSIONS: In settings with limited access to ultrasound, and in women who had been treated with P. falciparum malaria, SFH may be the most useful antenatal tool to date a pregnancy when women present first in second and third trimester. The Ballard postnatal maturation assessment has a limited role and lacks precision. Improving ultrasound facilities and skills, and early attendance, together with the development of new technologies such as automated image analysis and new postnatal methods to assess gestational age, are essential for the study and management of preterm birth in low-income settings.

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life.

Malaria incidence and prevalence during the first year of life in Nanoro, Burkina Faso: a birth-cohort study.

BACKGROUND: Infants are thought to be protected against malaria during the first months of life mainly due to passage of maternal antibodies. However, in high transmission settings, malaria in early infancy is not uncommon and susceptibility to the infections varies between individuals. This study aimed to determine malaria morbidity and infection during early childhood in rural Burkina Faso. METHODS: Malariometric indices were determined over 1-year follow-up in a birth cohort of 734 infants living in Nanoro health district. Clinical malaria episodes were determined by passive case detection at peripheral health centres while asymptomatic malaria infections were identified during  4 cross-sectional surveys at 3, 6, 9 and 12 months of age. Plasmodium falciparum infections were detected by rapid diagnostic test and/or light microscopy (LM) and quantitative PCR (qPCR). RESULTS: In total, 717 clinical episodes were diagnosed by qPCR over 8335.18 person-months at risk. The overall malaria incidence was 1.03 per child-year and increased from 0.27 per child-year at 0-3 months of age to 1.92 per child-year at 9-12 months of age. Some 59% of children experienced at least one clinical episode with a median survival time estimated at 9.9 months, while 20% of infants experienced the first episode before 6 months of age. The majority of the clinical episodes were attributable to microscopic parasitaemia (84.2%), and there was a positive correlation between parasite density and age (Spearman's rho = 0.30; P < 0.0001). Prevalence of asymptomatic infections was similar at 3, 6 and 9 months of age (17.7-20.1%) and nearly 1.6 times higher at 12 months (31.3%). Importantly, gametocyte prevalence among the LM-positive study population was 6.7%, but increased to 10% among asymptomatic infections. In addition, 46% of asymptomatic infections were only detected by qPCR suggesting that infants below 1 year are a potential reservoir for sustaining malaria transmission. Both symptomatic and asymptomatic infections showed marked seasonal distribution with the highest transmission period (July to December) accounting for about 89 and 77% of those infections, respectively. CONCLUSIONS: These findings indicate high and marked age and seasonal-dependency of malaria infections and disease during the first year of life in Nanoro, calling for intensified efforts to control malaria in rural Burkina Faso.

Diagnosing congenital malaria in a high-transmission setting: clinical relevance and usefulness of P. falciparum HRP2-based testing.

Congenital malaria diagnosis is challenging due to frequently observed low parasite density infections, while their clinical relevance during early infancy is not well characterized. In Nanoro health district (Burkina Faso), we determined the prevalence of congenital malaria by real-time quantitative PCR and we assessed the performance of rapid diagnosis test (RDT) and light microscopy (LM) to detect Plasmodium falciparum infections in cord-blood samples. In addition, we examined the usefulness of P. falciparum Histidine Rich Protein2 (PfHRP2) as surrogate biomarker of infection and explored association between congenital malaria and clinical outcomes. A prevalence of congenital malaria by qPCR of 4% (16/400) was found, which increased to 10% among newborns from mothers infected at delivery. RDT and LM showed poor performances indicating limited utility for congenital malaria screening in cord blood. Because PfHRP2 detection in cord blood could be affected by transplacental passage of parasite antigens, PfHRP2 might not be used as a surrogate biomarker of congenital malaria infections. There was no evidence of a significant clinical impact of congenital malaria on infant's health from birth to 59 days of life. Case control studies including long-term follow up may provide additional understanding on the relevance of neonatal malaria infections.

Safe and efficacious artemisinin-based combination treatments for African pregnant women with malaria: a multicentre randomized control trial.

BACKGROUND: Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her offspring. Unfortunately, there is insufficient information on the safety and efficacy of most antimalarials in pregnancy. Indeed, clinical trials assessing antimalarial treatments systematically exclude pregnancy for fear of teratogenicity and embryotoxicity. The little available information originates from South East Asia while in sub-Saharan Africa such information is still limited and needs to be provided. DESIGN: A Phase 3, non-inferiority, multicentre, randomized, open-label clinical trial on safety and efficacy of 4 ACT when administered during pregnancy was carried out in 4 African countries: Burkina Faso, Ghana, Malawi and Zambia. This is a four arm trial using a balanced incomplete block design. Pregnant women diagnosed with malaria are randomised to receive either amodiaquine-artesunate (AQ-AS), dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine (AL), or mefloquine-artesunate (MQAS). They are actively followed up until day 63 post-treatment and then monthly until 4-6 weeks post-delivery. The offspring is visited at the time of the first birthday. The primary endpoint is treatment failure (PCR adjusted) at day 63 and safety profiles. Secondary endpoints included PCR unadjusted treatment failure up to day 63, gametocyte carriage, Hb changes, placenta malaria, mean birth weight and low birth weight. The primary statistical analysis will use the combined data from all 4 centres, with adjustment for any centre effects, using an additive model for the response rates. This will allow the assessment of all 6 possible pair-wise treatment comparisons using all available data. DISCUSSION: The strength of this trial is the involvement of several African countries, increasing the generalisability of the results. In addition, it assesses most ACTs currently available, determining their relative '-value-' compared to others. The balanced incomplete block design was chosen because using all 4-arms in each site would have increased complexity in terms of implementation. Excluding HIV-positive pregnant women on antiretroviral drugs may be seen as a limitation because of the possible interactions between antiretroviral and antimalarial treatments. Nevertheless, the results of this trial will provide the evidence base for the formulation of malaria treatment policy for pregnant women in sub-Saharan Africa.

The impact of clinical research activities on communities in rural Africa: the development of the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso.

BACKGROUND: The opportunities for developing new drugs and vaccines for malaria control look brighter now than ten years ago. However, there are few places in sub-Saharan Africa with the necessary infrastructure and expertise to support such research in compliance to international standards of clinical research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) was founded in 2008 to provide a much-needed GCP-compliant clinical trial platform for an imminent large-scale Phase 3 malaria vaccine trial. A dynamic approach was used that entailed developing the required infrastructure and human resources, while engaging local communities in the process as key stakeholders. This provided a better understanding and ownership of the research activities by the local population. CASE DESCRIPTION: Within five years (2008-2013), the CRUN set up a fully and well-equipped GCP-compliant clinical trial research facility, which enabled to attract 25 grants. The research team grew from ten health workers prior to 2008 to 254 in 2013. A Health and Demographic Surveillance System (HDSS), which covers a total population of about 60,000 people in 24 villages was set up in the district. The local community contributed to the development of the facility through the leadership of the king and the mayor of Nanoro. As a result of their active advocacy, the government extended the national electrical grid to the new research center, and later to the entire village. This produced a positive impact on the community's quality of life. The quality of health care improved substantially, due to the creation of more elaborate clinical laboratory services and the acquisition of state-of-the-art equipment. CONCLUSION: Involving the community in the key steps of establishing the centre provided the foundation for what was to become the CRUN success story. This experience demonstrates that when clinical trials research sites are carefully developed and implemented, they can have a positive and powerful impact on local communities in resource-poor settings, well beyond the task of generating expected study data.

A new oxygenated ursane derivative from Canthium multiflorum.

A new ursane derivative, 3-oxo-15alpha,19alpha-dihydroxyursa-1,12-dien-28-oic acid, was isolated from the roots of Canthium multiflorum (Rubiaceae) along with 10-O-acetylgeniposidic acid, 6,7-dimethoxycoumarin, hymexelsin, scopoletin, and 5,6,7-trimethoxycoumarin.

Cytotoxic kurubasch aldehyde from Trichilia emetica.

Kurubasch aldehyde, a sesquiterpenoid with an hydroxylated humulene skeleton, was isolated as free alcohol from Trichilia emetica Vahl. (Meliaceae), belonging to the order Sapindales. Related substances have been previously found in plants as esters of aromatic acids, and these plants were species belonging to the distant order Apiales. This is the first report of humulenes found in the genus Trichilia and only the second of humulenes in the order Sapindales. The aldehyde is a modest inhibitor of the growth of Plasmodium falciparum (IC50 76 microM) and slow-proliferating breast cancer cells MCF7 (78 microM), but a potent inhibitor of proliferation of S180 cancer cells (IC50 7.4 microM).

[Parasitological resistance of Plasmodium falciparum to antimalarial drugs: what physicians should keep in mind]. / Attitude à propos de la résistance parasitologique de Plasmodium falciparum aux antipaludiques.

Plasmodium falciparum drug resistance has considerably modified the attitude of physicians in terms of malaria case management. However, a bad understanding of the resistance phenomenon can lead to non-appropriate therapeutic and/or public health practices. The objective of this paper was to contribute to clarify the concept of parasitological resistance by analysing the different types of resistance observed in vivo. We showed through some examples that the precision of in vivo parasitological results depends on the type of microscopical technique used. We also showed that the classification system into resistance levels RI, RII, and RIII does not correspond to an increase in the resistance of the parasite itself but rather to an increase in the proportion of the resistant strains compared to the sensitive ones circulating in a given population. Mutant strains are circulating in low proportions as long as there is no selective drug pressure. They can be first detected in vitro and, later on, when their proportion increase, they are detected in vivo, first in non-immune subjects and later in semi-immune subjects. Therefore, the role of the host immunity is important in malaria drug resistance. To conclude, increasing use of antimalarial drugs (especially in monotherapy) cannot thwart the resistance, but rather leads to the selection of mutants strains. As the proportion of the mutant strains increases compared to the sensitive (wild) ones, it will reach the microscopic detection level and then, the clinical level. It is important that physicians involved in malaria case management understand these notions in order to avoid non-appropriate therapeutic decisions.

Antiplasmodial compounds from Cochlospermum tinctorium.

Fractionation of an ethanol extract of roots of Cochlospermum tinctorium afforded five compounds: 3-O-E-p-coumaroylalphitolic acid (1), cochloxanthin (2), dihydrocochloxanthin (3), alphitolic acid (4), and 1-hydroxytetradecan-3-one (5). This is the first example of a 1-hydroxyalkan-3-one obtained from plant material after gentle workup. The antiplasmodial activities of the compounds were determined, and the IC(50) value of 3-O-E-p-coumaroylalphitolic acid was 2.3 microM.