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Global malaria cases have not been significantly reduced over the last three years although more than USD 3 billion was invested in malaria control and elimination. The reasons for this stagnation are highly complex and multi-factorial. It remains that almost three billion treatment courses were supplied over the period 2010-2017: 30% of them without malaria tests, and some with suboptimal doses leading to the risk of selection of resistant parasites. An antimalarial stewardship program should be implemented at the healthcare provider, physician, pharmacist, medical student, and population levels. This would significantly reinforce the impact of international guidelines and national malaria program policies and fill the gap between recommendations and actual practices., (© A.-L. Bienvenu et al., published by EDP Sciences, 2019.)

Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels., Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels., Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2., Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

Background: Malaria is a major public health problem in Mali and diagnosis is typically based on microscopy. Microscopy requires a well trained technician, a reliable power source, a functioning microscope and adequate supplies. The scarcity of resources of community health centres (CHC) does not allow for such a significant investment in only one aspect of malaria control. In this context, Rapid Diagnostic Tests (RDTs) may improve case management particularly in remote areas., Methods: This multicentre study included 725 patients simultaneously screened with OptiMal-IT test and thick smears for malaria parasite detection. While evaluating the therapeutic efficacy of choroquine in 2 study sites, we compared the diagnostic values of thick smear microscopy to OptiMal-IT test applying the WHO 14 days follow-up scheme using samples collected from 344 patients., Results: The sensitivity and the specificity of OptiMal-IT compared to thick smear was 97.2% and 95.4%, whereas the positive and negative predictive values were 96.7 and 96.1%, respectively. The percent agreement between the two diagnostic tests was 0.93. The two tests were comparable in detecting malaria at day 0, day 3 and day 14. The only difference was observed at day 7 due to high gametocytemia. Subjectively, health care providers found OptiMal-IT easier to use and store under field conditions., Conclusion: OptiMal-IT test revealed similar results when compared to microscopy which is considered the gold standard for malaria diagnostics. The test was found to have a short processing time and was easier to use. These advantages may improve malaria case management by providing a diagnostic and drug efficacy follow-up tool to peripheral health centres with limited resources.

In the 20th century malaria remains a major problem of public health in sub-Saharan Africa. This haemosporidium discovered in Africa by Laveran in 1880, kills one child every 30 seconds which amounts to three "tsunami" flowing each year into the African continent. The current international solidarity raises new hopes as regards the possibility to suppress the morbidity effects on the population's health condition. In order to be efficient, today's strategies (impregnated mosquito nets, intermittent preventive treatments, artemisinin based combination therapy) should reach at least 80% of the targeted population (pregnant women and children). By 2025, the uncontrolled urbanization of the African population and the social disorders will make a new population a target for malaria. The new data of functional genomics and proteonics open new avenues of research for new mechanisms, new therapeutics and vaccine targets and new tools of diagnosis and prognosis. The current candidate vaccines of the first generation have allowed the development of African competences in clinical trials of international standard. Although they represent scientific advances they will not resolve the problem of public health. Research on candidate vaccines of 2nd and 3rd generation remains a challenge for the international scientific community. Africa should play a determining role in this process. Scientific information on the field remains essential for these generations of new anti-malarial vaccines. The ethical aspects regarding those clinical trials and actions of public health and research remain an universal necessity Deontology and ethics are two complementary approaches for the good practice of medicine and research of a good practitioner. For the protection and advantages of the patient and/or volunteer of the research are the cornerstones of the ethical approach. The scientific quality of a research protocol submitted to an independent research ethics committee and the volunteer 's informed consent are universal ethical obligations. For the quality of ethics observance in a country reflects best the quality of the efficiency of its research system and its democracy.

Abstract Background Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic. Methods A systematic review of the literature maintained in the bibliographic databases accessible through the PubMed, ScienceDirect and Web of Science search engines was performed to identify research studies on ACT occurring at Mali study sites. Selected studies included trials occurring at Mali study sites with reported polymerase chain reaction (PCR)-corrected adequate clinical and parasite response rates (ACPRcs) at 28 days. Data were stratified by treatment arm (artemether–lumefantrine (AL), the first-line treatment for falciparum malaria in Mali and non-AL arms) and analysed using random-effects, meta-analysis approaches. Results A total of 11 studies met the inclusion criteria, and a risk of bias assessment carried out by two independent reviewers determined low risk of bias among all assessed criteria. The ACPRc for the first-line AL at Mali sites was 99.0% (95% CI (98.3%, 99.8%)), while the ACPRc among non-AL treatment arms was 98.9% (95% CI (98.3%, 99.5%)). The difference in ACPRcs between non-AL treatment arms and AL treatment arms was not statistically significant (p = .752), suggesting that there are potential treatment alternatives beyond the first-line of AL in Mali. Conclusions ACT remains highly efficacious in treating uncomplicated falciparum malaria in Mali. Country-specific meta-analyses on ACT are needed on an ongoing basis for monitoring and evaluating drug efficacy patterns to guide local malaria treatment policies, particularly in the wake of observed artemisinin resistance in Southeast Asia and partial resistance in Rwanda.

Abstract Background Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality. Methods A WHO standard protocol was used to assess efficacy of the combinations artesunate–amodiaquine (AS–AQ Winthrop®), dihydroartemisinin–piperaquine (DHA–PPQ, Eurartesim®) and artemether–lumefantrine (AM–LM, Coartem®) taken under supervision and respecting pharmaceutical recommendations. The study enrolled for each treatment arm 212 children aged 6–59 months living in Maradi (Niger) and suffering with uncomplicated falciparum malaria. The Kaplan–Meier 42-day PCR-adjusted cure rate was the primary outcome. A standardized parasite clearance estimator was used to assess delayed parasite clearance as surrogate maker of suspected artemisinin resistance. Results No early treatment failures were found in any of the study treatment arms. The day-42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS–AQ, DHA–PPQ and AM–LM arms, respectively. The reinfection rate (expressed also as Kaplan–Meier estimates) was higher in the AM–LM arm (32.4%) than in the AS–AQ (13.8%) and the DHA–PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26 and 0.25 per hour for AS–AQ, DHA–PPQ and AM–LM, respectively. Conclusions All the three treatments evaluated largely meet WHO criteria (at least 95% efficacy). AS–AQ and AL–LM may continue to be used and DHA–PPQ may be also recommended as first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite clearance rate were consistent with reference values indicating no suspected artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug efficacy should continue. Trial registration details Registry number at ClinicalTrial.gov: NCT01755559

Abstract Background Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Methods Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Results Eight thousand eight hundred ninety-seven patients (77.0%

In Mali, since 2007, artemether-lumefantrine has been the first choice against uncomplicated malaria. Despite its effectiveness, a rapid selection of markers of resistance to partner drugs has been documented. This work evaluated the treatment according to the World Health Organization’s standard 28-day treatment method. The primary endpoint was the clinical and parasitological response corrected by a polymerase chain reaction. It was more than 99.9 percent, the proportion of patients with anemia significantly decrease compared to baseline (p < 0.001), and no serious events were recorded. Plasmodium falciparum remains sensitive to artemether-lumefantrine in Mali.

Abstract Background The widespread use of artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria makes it important to gather and analyse information on its tolerability. Methods An individual-patient tolerability analysis was conducted using data from eight randomized controlled clinical trials conducted at 17 sites in nine sub-Saharan countries comparing ASAQ to other anti-malarial treatments. All patients who received at least one dose of the study drug were included in the analysis. Differences in adverse event (AE) and treatment emergent adverse event (TEAE) were analysed by Day 28. Results Of the 6,179 patients enrolled (74% Conclusion ASAQ was comparatively well-tolerated. Safety information is important, and must be collected and analysed in a standardized way. TEAEs are a more objective measure of treatment-induced toxicity.

Background: The use of pyronaridine-artesunate (PA) has been associated with scarce transaminitis in patients. This analysis aimed to evaluate the hepatic safety profile of repeated treatment with PA versus artemether-lumefantrine (AL) in patients with consecutive uncomplicated malaria episodes in Bobo-Dioulasso, Burkina Faso. Methods: This study analysed data from a clinical trial conducted from 2012 to 2015, in which participants with uncomplicated malaria were assigned to either PA or AL arms and followed up to 42 days. Subsequent malaria episodes within a 2-years follow up period were also treated with the same ACT initially allocated. Transaminases (AST/ALT), alkaline phosphatase (ALP), total and direct bilirubin were measured at days 0 (baseline), 3, 7, 28 and on some unscheduled days if required. The proportions of non-clinical hepatic adverse events (AEs) following first and repeated treatments with PA and AL were compared within study arms. The association of these AEs with retreatment in each arm was also determined using a logistic regression model. Results: A total of 1379 malaria episodes were included in the intention to treat analysis with 60% of all cases occurring in the AL arm. Overall, 179 non-clinical hepatic AEs were recorded in the AL arm versus 145 in the PA arm. Elevated ALT was noted in 3.05% of treated malaria episodes, elevated AST 3.34%, elevated ALP 1.81%, and elevated total and direct bilirubin in 7.90% and 7.40% respectively. Retreated participants were less likely to experience elevated ALT and AST than first episode treated participants in both arms. One case of Hy's law condition was recorded in a first treated participant of the PA arm. Participants from the retreatment group were 76% and 84% less likely to have elevated ALT and AST, respectively, in the AL arm and 68% less likely to present elevated ALT in the PA arm. In contrast, they were almost 2 times more likely to experience elevated total bilirubin in both arms. Conclusions: Pyronaridine-artesunate and artemether-lumefantrine showed similar hepatic safety when used repeatedly in participants with uncomplicated malaria. Pyronaridine-artesunate represents therefore a suitable alternative to the current first line anti-malarial drugs in use in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality. Methods: A WHO standard protocol was used to assess efficacy of the combinations artesunate-amodiaquine (AS-AQ Winthrop®), dihydroartemisinin-piperaquine (DHA-PPQ, Eurartesim®) and artemether-lumefantrine (AM-LM, Coartem®) taken under supervision and respecting pharmaceutical recommendations. The study enrolled for each treatment arm 212 children aged 6-59 months living in Maradi (Niger) and suffering with uncomplicated falciparum malaria. The Kaplan-Meier 42-day PCR-adjusted cure rate was the primary outcome. A standardized parasite clearance estimator was used to assess delayed parasite clearance as surrogate maker of suspected artemisinin resistance. Results: No early treatment failures were found in any of the study treatment arms. The day-42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS-AQ, DHA-PPQ and AM-LM arms, respectively. The reinfection rate (expressed also as Kaplan-Meier estimates) was higher in the AM-LM arm (32.4%) than in the AS-AQ (13.8%) and the DHA-PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26 and 0.25 per hour for AS-AQ, DHA-PPQ and AM-LM, respectively. Conclusions: All the three treatments evaluated largely meet WHO criteria (at least 95% efficacy). AS-AQ and AL-LM may continue to be used and DHA-PPQ may be also recommended as first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite clearance rate were consistent with reference values indicating no suspected artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug efficacy should continue. [ABSTRACT FROM AUTHOR]

Background: Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity.Methods: Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models.Results: Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop of -12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15's, the mean Hb decline between day 0-3 was -4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline. Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28. There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia.Conclusion: On presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1-2, followed by a linear increase through follow-up. The degree of the early Hb dip is determined by pre-treatment parasitaemia and parasite clearance rates. Hb trends and rick of anaemia are independent of treatment. [ABSTRACT FROM AUTHOR]

Background: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood. Methods: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case-control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali. Results: Complement and toll-like receptor (TLR) pathways were differentially expressed, with severe cases showing higher expression of the C1q, TLR2, TLR4, TLR8, and CR1 genes. Other genes previously associated with malaria pathogenesis, GZMB, FOS and HSPA6, were also higher among severe cases. TLR2, TLR4, TLR8, CR1, GZMB, FOS, and HSPA6 genes were expressed at lower levels in severe cases at late convalescence. Conclusions: Overexpression of genes previously associated with uncomplicated malaria was associated with severe disease. Low baseline expression of these genes may represent candidate markers for severe malaria. Despite the small sample size, results of this pilot study offer promising targets for follow-up analyses. [ABSTRACT FROM AUTHOR]

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication. [ABSTRACT FROM AUTHOR]

Background: Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. Methods: Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a nonfalciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. Results: P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. Conclusions: Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites. [ABSTRACT FROM AUTHOR]

Background: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach. Methods and Findings: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. Conclusions: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated. Trial Registration: ClinicalTrials.gov Pan African Clinical trials Registry [ABSTRACT FROM AUTHOR]

Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits. WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the “Global Technical Strategy” and 21 countries are aiming to eliminate malaria by 2020. The commitment to achieve these targets should be celebrated. However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever. Over 180 experts across multiple disciplines are engaged in the Malaria Eradication Research Agenda (malERA) Refresh process to address problems that need to be solved. The result is a research and development agenda to accelerate malaria elimination and, in the longer term, transform the malaria community’s ability to eradicate it globally.

In patients with malaria, parasitaemia is usually estimated by assuming 8000 white cell counts (WCC) per microlitre of blood. In a sample of 3044 African children under 5 years of age with uncomplicated falciparum malaria, parasitaemia estimated using standardised WCC was compared to parasitaemia calculated based on each child's own WCC. The two methods produced comparable results. However, WCC were >8000 in under-fives with an inverse relationship with age, resulting in the standard approximation method significantly underestimating parasitaemia in the youngest age group and overestimating parasitaemia in the oldest age groups. [ABSTRACT FROM AUTHOR]

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Abstract: In vitro susceptibility to antimalarial drugs of Malian Plasmodium falciparum isolates collected between 2004 and 2006 was studied. Susceptibility to chloroquine and to three artemisinin-based combination therapy (ACT) component drugs was assessed as a first, to our knowledge, in vitro susceptibility study in Mali. Overall 96 Malian isolates (51 from around Bamako and 45 collected from French travellers returning from Mali) were cultivated in a CO2 incubator. Fifty percent inhibitory concentrations (IC50s) were measured by either hypoxanthine incorporation or Plasmodium lactate dehydrogenase (pLDH) ELISA. Although the two sets of data were generated with different methods, the global IC50 distributions showed parallel trends. A good concordance of resistance phenotype with pfcrt 76T mutant genotype was found within the sets of clinical isolates tested. We confirm a high prevalence of P. falciparum in vitro resistance to chloroquine in Mali (60–69%). While some isolates showed IC50s close to the cut-off for resistance to monodesethylamodiaquine, no decreased susceptibility to dihydroartemisinin or lumefantrine was detected. This study provides baseline data for P. falciparum in vitro susceptibility to ACT component drugs in Mali. [Copyright &y& Elsevier]

Summary: We report the results of an in vivo antimalarial efficacy study with chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) conducted between 2003 and 2004 in Koumantou, southern Mali. A total of 244 children were included in the study; 210 children were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescence from re-infection. Global failure proportions at Day 14, without taking into account re-infections, were 44.2% (95% CI 34.9–53.5%) in the CQ group and 2.0% (95% CI 0.0–4.8%) in the SP group. PCR-adjusted failure proportions at Day 28 were even higher in the CQ group (90.5% (95/105), 95% CI 84.8–96.2%) and relatively low in the SP group (7.0% (7/100), 95% CI 1.9–12.1%). These results show that CQ is no longer efficacious in Koumantou. The use of SP in monotherapy is likely to compromise its efficacy. We recommend the use of artemisinin-based combination therapy as first-line treatment for uncomplicated Plasmodium falciparum malaria in Koumantou. [Copyright &y& Elsevier]