Abdoulaye Djimde

• PharmD, PhD
• Managing Director at Université des Sciences, des Techniques et des Technologies de Bamako

Dihydroartemisinin-piperaquine (DHA-PPQ) is being recommended in Africa for the management of uncomplicated Plasmodium falciparum malaria and for chemoprevention strategies, based on the ability of piperaquine to delay re-infections. Although therapeutic resistance to piperaquine has been linked to increased copy number in plasmepsin-coding parasit...

Non-falciparum species causing malaria in humans are considered neglected in the fight toward malaria elimination. Recent data highlight the increasing contribution of Plasmodium malariae to malaria morbidity and mortality. In this study, the susceptibility of P. malariae and Plasmodium falciparum to current antimalarial drugs was compared to advan...

Plasmodium malariae is the third most prevalent human malaria parasite species and contributes significantly to morbidity. Nevertheless, our comprehension of this parasite’s biology remains limited, primarily due to its frequent co-infections with other species and the lack of a continuous in vitro culture system. To effectively combat and eliminat...

Sulfadoxine-pyrimethamine (SP), despite the emergence and spread of mutations in dhfr and dhps genes associated with lower treatment efficacy, is still recommended alone or in combination by the WHO for preventive treatment in pregnant women, children and infants. Therefore, it is important to understand the evolution of P. falciparum dhfr and dhps...

Le paludisme urbain est devenu un important défi pour nombre de pays africains à cause de l’urbanisation effrénée et de l’accroissement de la population. La transmission urbaine chez des sujets non prémunis peut constituer un problème de santé publique dans les années à venir. L’objectif de cette étude était d’évaluer les variations spatiales de l’...

Background: Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans, such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in West Africa are available. Our previous findings from a study investigating emergi...

The selection and combination of dose regimens for antimalarials involve complex considerations including pharmacokinetic and pharmacodynamic interactions. In this study, we use immediate ex vivo P. falciparum field isolates to evaluate the effect of cabamiquine and pyronaridine as standalone treatments and in combination therapy. We feed the data...

The developmental decision made by malaria parasites to become sexual underlies all malaria transmission. Here, we describe a rich atlas of short- and long-read single-cell transcriptomes of over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development. We used the atlas to explore transcriptional modules and exon...

Background CYP2C8 is responsible for the metabolism of 5% of clinically prescribed drugs, including antimalarials, anti-cancer and anti-inflammatory drugs. Genetic variability is an important factor that influences CYP2C8 activity and modulates the pharmacokinetics, efficacy and safety of its substrates. Results We profiled the genetic landscape o...

Dihydroartemisinin-piperaquine is efficacious for the treatment of uncomplicated malaria and its use is increasing globally. Despite the positive results in fighting malaria, inhibition of the Kv11.1 channel (hERG; encoded by the KCNH2 gene) by piperaquine has raised concerns about cardiac safety. Whether genetic factors could modulate the risk of...

Background Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine–artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM). Methods An integrated safety analysis of individual patient data from three randomized clinical trials included...

Introduction: Trichomonas vaginalis and Mycoplasma are common causes of sexually transmitted infections, but limited prevalence data are available in Senegal. This study aimed to determine the prevalence of T. vaginalis and genital mycoplasma infection among women in Dakar. Materials and Methods: A retrospective study was carried out between 2016 a...

Background: In Mali, Chloroquine has been abandoned in 2005 because of the high in vivo and in vitro resistance rate of Plasmodium falciparum to this molecule. Artemisinin-based combination therapies (ACT) are currently recommended to treat uncomplicated malaria. Few antimalarials are in development. Assessing the prevalence of known antimalarial d...

Background One of the key obstacles to malaria elimination is largely attributed to Plasmodium vivax’s ability to form resilient hypnozoites in the host liver that cause relapsing infections. As a result, interruption of P. vivax transmission is difficult. P. vivax transmission occurs in Duffy-positive individuals and have been mainly thought to be...

Background CYP2C8 polymorphisms can impair the metabolism of the antimalarial amodiaquine and influence exposure to the key active metabolite desethylamodiaquine (DEAQ). CYP2C8*2 entailed to slow metabolism phenotype is the most frequent allele in Africa. Here we study the association between CYP2C8*2 carriage and DEAQ D7 drug level for repeated tr...

Imidazolopiperazine (IPZ), KAF156, a close analogue of GNF179, is a promising antimalarial candidate. IPZ is effective against Plasmodium falciparum and Plasmodium vivax clinical malaria in human with transmission blocking property in animal models and effective against liver stage parasites. Despite these excellent drug efficacy properties, in vit...

Up-to-date knowledge of key epidemiological aspects of each Plasmodium species is necessary for making informed decisions on targeted interventions and control strategies to eliminate each of them. This study aims to describe the epidemiology of plasmodial species in Mali, where malaria is hyperendemic and seasonal. Data reports collected during hi...

Malaria elimination may never succeed without the implementation of transmission-blocking strategies. The transmission of Plasmodium spp. parasites from the human host to the mosquito vector depends on circulating gametocytes in the peripheral blood of the vertebrate host. Once ingested by the mosquito during blood meals, these sexual forms undergo...

The developmental decision made by malaria parasites to become sexual underlies all malaria transmission. Here, we describe a rich atlas of short and long-read single-cell transcriptomes of over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development. We used the atlas to explore transcriptional modules and exon u...

Background Effective approaches to fight against malaria include disease prevention, an early diagnosis of malaria cases, and rapid management of confirmed cases by treatment with effective antimalarials. Artemisinin-based combination therapies are first-line treatments for uncomplicated malaria in endemic areas. However, cases of resistance to art...

One of the key obstacles to malaria elimination is largely attributed to Plasmodium vivax’s ability to form resilient hypnozoites in the host liver that cause relapsing infections. As a result, interruption of P. vivax transmission is difficult. P. vivax transmission occurs in Duffy-positive individuals and have been mainly thought to be absent in...

Malaria treatments resulted in the decline of the deadliest Plasmodium falciparum globally while species, such as P. ovale, infections have been increasingly detected across sub-Saharan Africa. Currently, no experimental drug sensitivity data are available to guide effective treatment and management of P. ovale infections, which is necessary for ef...

Objectives: In low-income settings with limited access to diagnosis, COVID-19 information is scarce. In September 2020, after the first COVID-19 wave, Mali reported 3086 confirmed cases and 130 deaths. Most reports originated from Bamako, with 1532 cases and 81 deaths (2.42 million inhabitants). This observed prevalence of 0.06% appeared very low....

Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in the Kolikoro and Sikasso regions are available, hence the interest in investigating the differe...

Objective: Malaria is a major public health problem in Niger. It accounts for 28% of all illnesses in the country and 50% of all death records. The objective of our study was to analyze the role played by private pharmacies in the management of uncomplicated malaria. Material and methods: This are a descriptive analytical cross-sectional study, con...

Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host's immunity and genes involved in controlling the parasitic infection can inform the development of blood-stage malaria vaccines. This stud...

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot sample...

Plasmodium malariae , a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it presents mostly as coinfections with the dominant P. falciparum . Completion of its reference genome has paved the way to further understand its biology a...

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimala...

Studying malaria transmission biology using scRNA-sequencing provides information on within-host strain diversity and transcriptional states. Here, we comment on our collaborative efforts at establishing single-cell capacities in sub-Saharan Africa and the challenges encountered in Mali’s endemic setting.

The discovery and development of transmission-blocking therapies challenge malaria elimination and necessitate standard and reproducible bioassays to measure the blocking properties of antimalarial drugs and candidate compounds. Most of the current bioassays evaluating the transmission-blocking activity of compounds rely on laboratory-adapted Plasm...

Background: CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent P. falciparum infection in a region in which the infection is endemic is unknown. Methods: We conducted a phase 2 trial to assess the safety and efficacy...

Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental chang...

Mali is a developing country facing several health challenges with a high rate of tuberculosis (TB) and a moderate HIV infection burden. Little is known or done about fungal diseases, yet they represent a significant public health problem in certain populations. The aim of this study was to estimate the national burden of fungal disease, and summar...

Intermittent preventive treatment of malaria among schoolchildren (IPTsc) reduces clinical malaria, asymptomatic parasitemia, and anemia. The effects of IPTsc by gender have not been studied longitudinally. We investigated overall IPTsc efficacy and conducted a secondary analysis to explore gender-specific differences. We enrolled schoolchildren ag...

Structural biology is an essential tool for understanding the molecular basis of diseases, which can guide the rational design of new drugs, vaccines, and the optimisation of existing medicines. However, most African countries do not conduct structural biology research due to limited resources, lack of trained persons, and an exodus of skilled scie...

Plasmodium malariae , a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it presents mostly as coinfections with the dominant P. falciparum . Completion of its reference genome has paved the way to further understand its biology a...

Context In low-income settings where access to biological diagnosis is limited, data on the spread of the COVID-19 epidemic are scarce. In September 2020, after the first COVID-19 wave, Mali reported 3,086 confirmed cases and 130 deaths. Most reports originated form Bamako, the capital city, with 1,532 reported cases and 81 deaths for an estimated...

Failure to account for genetic diversity of antigens during vaccine design may lead to vaccine escape. To evaluate the vaccine escape potential of antigens used in vaccines currently in development or clinical testing, we surveyed the genetic diversity, measured population differentiation, and performed in silico prediction and analysis of T-cell e...

Throughout a phase IIIb/IV efficacy study of repeated treatment with four artemisinin-based combination therapies, significant heterogeneity was found in the number of clinical episodes experienced by individuals during the 2-year follow-up. Several factors, including host, parasite, and environmental factors, may contribute to the differential mal...

The addition of a third anti-malarial drug matching the pharmacokinetic characteristics of the slowly eliminated partner drug in artemisinin-based combination therapy (ACT) has been proposed as new therapeutic paradigm for the treatment of uncomplicated falciparum malaria. These triple artemisinin-based combination therapy (TACT) should in theory m...

Background A recent trial in Burkina Faso and Mali showed that combining seasonal RTS,S/AS01 E malaria vaccination with seasonal malaria chemoprevention (SMC) substantially reduced the incidence of uncomplicated and severe malaria in young children compared to either intervention alone. Given the possible negative effect of malaria on nutrition, th...

Background In 2012, seasonal malaria chemoprevention (SMC) was recommended as policy for malaria control by the World Health Organization (WHO) in areas of highly seasonal malaria transmission across the Sahel sub-region in Africa along with monitoring of drug resistance. We assessed the long-term impact of SMC on Plasmodium falciparum resistance t...

Leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae . Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for...

Background: A trial in young African children showed that combining seasonal vaccination with the RTS,S/AS01E vaccine with seasonal malaria chemoprevention reduced the incidence of uncomplicated and severe malaria substantially compared to either intervention given alone. This paper reports the anti-circumsporozoite antibody response to seasonal R...

Next-generation sequencing (NGS) has become a necessary tool for genomic epidemiology. Even though the utility of genomics in human health has been proved, genomic surveillance has never been as important as during the COVID-19 pandemic. This has been demonstrated by the recent use of genomic surveillance to detect new variants of SARS-CoV-2 in the...

Serological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O’nyong-nyong virus (ONNV) as a case study. We develop a...

Genetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens ( msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom...

Background: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy that was adopted in Mali as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study was designed to measure the efficacy of artemether-lumefantrine and to assess the selection of the P. falciparum chloroquine resistance transport...

Introduction Les résultats de plusieurs recherches montrent que le paludisme impacte négativement le niveau de vie des ménages, mais peu d’études se sont intéressées à l’effet immédiat de la réduction de diminution du paludisme sur l’économie et les comportements des ménages par rapport à l’investissement dans le capital humain. L’objectif de cette...

Artemisinin resistance (AR) emerged in South East Asia 13 years ago and the identification of the resistance conferring molecular marker, Plasmodium falciparum Kelch 13 (Pfk13), 7 years ago has provided an invaluable tool for monitoring AR in malaria endemic countries. Molecular Pfk13 surveillance revealed the resistance foci in the Greater Mekong...

Objectives: To evaluate Plasmodium malariae susceptibility to current and lead candidate antimalarial drugs. Methods: We conducted cross-sectional screening and detection of all Plasmodium species malaria cases, which were nested within a longitudinal prospective study, and an ex vivo assessment of efficacy of a panel of antimalarials against P....

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 th...

Background Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectivenes...

Previous studies have shown that a single season of intermittent preventive treatment in schoolchildren (IPTsc) targeting the transmission season has reduced the rates of clinical malaria, all-cause clinic visits, asymptomatic parasitemia, and anemia. Efficacy over the course of multiple years of IPTsc has been scantly investigated. Methods: An o...

Background: Previous controlled studies demonstrated seasonal malaria chemoprevention (SMC) reduces malaria morbidity by >80% in children aged 3-59 months. Here, we assessed malaria morbidity after large-scale SMC implementation during a pilot campaign in the health district of Koutiala, Mali. Methods: Starting in August 2012, children received...

Background Artemisinin resistance described as increased parasite clearance time (PCT) is rare in Africa. More sensitive methods such as qPCR might better characterize the clearance phenotype in sub-Saharan Africa. Methods PCT is explored in Mali using light microscopy and qPCR after artesunate for uncomplicated malaria. In two villages, patients...

Background Electrocardiographic QT interval prolongation is the most widely used risk marker for ventricular arrhythmia potential and thus an important component of drug cardiotoxicity assessments. Several antimalarial medicines are associated with QT interval prolongation. However, interpretation of electrocardiographic changes is confounded by th...

Plasmodium falciparum remains one of the leading causes of child mortality, and nearly half of the world’s population is at risk of contracting malaria. While pathogenesis results from replication of asexual forms in human red blood cells, it is the sexually differentiated forms, gametocytes, which are responsible for the spread of the disease. For...

Plasmodium falciparum remains one of the leading causes of child mortality, and nearly half of the world’s population is at risk of contracting malaria. While pathogenesis results from replication of asexual forms in human red blood cells, it is the sexually differentiated forms, gametocytes, which are responsible for the spread of the disease. For...

Background: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin der...

Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods: Antimalarial studies typically report the...

Understanding genomic variation and population structure of Plasmodium falciparum across Africa is necessary to sustain progress toward malaria elimination. Genome clustering of 2263 P. falciparum isolates from 24 malaria-endemic settings in 15 African countries identified major western, central, and eastern ancestries, plus a highly divergent Ethi...

While Plasmodium falciparum continues to be the main target for malaria elimination, other Plasmodium species persist in Africa. Their clinical diagnosis is uncommon while rapid diagnostic tests (RDTs), the most widely used malaria diagnostic tool, are only able to distinguish between P. falciparum and non-falciparum species, the latter as ‘pan-spe...

The intensification of malaria control interventions has resulted in its global decline, but it remains a significant public health burden especially in sub-Saharan Africa (sSA). Knowledge on the parasite diversity, its transmission dynamics, mechanisms of adaptation to environmental and interventional pressures could help refine or develop new con...

Background WHO recommended seasonal malaria chemoprevention (SMC) in 2012 for Sahel countries in Africa with the aim to reduce malaria among children under 5 years old by using sulphadoxine-pyrimethamine and amodiaquine (SP+AQ). This strategy was scaled up in Mali from 2012. The use of millions of doses of SP+AQ could generate potential Plasmodium...

Background Despite major progress in the past decade, malaria remains a major public health problem in sub-Saharan Africa. West and Central Africa account for nearly 2/3 of the burden currently attributable to falciparum malaria. Artemisinin-based combination therapies (ACT) are a cornerstone of our strategy for controlling and eventually eliminati...

Dihydroartemisinin/piperaquine (DHA/PPQ) is increasingly deployed as antimalaria drug in Africa. We report the detection in Mali of Plasmodium falciparum infections carrying plasmepsin 2 duplications (associated with piperaquine resistance) in 7/65 recurrent infections within 2 months after DHA/PPQ treatment. These findings raise concerns about the...

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms-many related to the structure or function of red blood cells-and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respi...