Karim TRAORE - Academia.edu (original) (raw)
Papers by Karim TRAORE
International Journal of Ethics Education
Background: Despite an increase in health research conducted in Africa, there are still inadequat... more Background: Despite an increase in health research conducted in Africa, there are still inadequate human resources with research ethics training and lack of local long-term training opportunities in research ethics. A research ethics training program named United States-Mali Research Ethics Training Program (US-Mali RETP) was established through a partnership between the George Washington University Milken Institute School of Public Health (GWSPH), USA and University of Sciences, Techniques & Technologies of Bamako (USTTB), to address the critical need for improved bioethics training, leadership, and policy in Mali. Methods: The aims of the capacity building programme are achieved by leveraging US and Africa-based expertise to strengthen research ethics education and capacity through: (1) intensive faculty development to design ethics training curricula; (2) development of a research ethics specialization within the existing Masters of Public Health program (MPH); and (3) establishi...
International Journal of Molecular Sciences, 2021
Background: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy t... more 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 transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genotypes that have been associated with drug resistance. Methods: A 28-day follow-up efficacy trial of artemether-lumefantrine was conducted in patients aged 6 months and older suffering from uncomplicated falciparum malaria in four different Malian areas during the 2009 malaria transmission season. The polymorphic genetic markers MSP2, MSP1, and Ca1 were used to distinguish between recrudescence and reinfection. Reinfection and recrudescence were then grouped as recurrent infections and analyzed together by PCR-restriction fragment length polymorphism (RFLP) to identify candid...
mSystems, 2021
Malaria parasites display antigens on the surface of infected red blood cells in the human host t... more Malaria parasites display antigens on the surface of infected red blood cells in the human host that facilitate attachment to blood vessels, contributing to the severity of infection. These antigens are highly variable, allowing the parasite to evade the immune system.
BackgroundEvaluation of local transmission epidemiology to characterize malaria risk is essential... more BackgroundEvaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) has been a major asset to this approach. This study aimed to characterize the local spatio-temporal pattern of malaria infection and clinical disease after implementation of Seasonal Malaria Chemoprevention (SMC) and Indoor Residual Spraying (IRS) in Bandiagara, a Malian town.MethodsFrom October 2017 to December 2018, an active and passive surveillance system was established in a cohort study of three hundred children aged from 6 months to 15 years old. Weekly time-series of clinical malaria and monthly time-series of asymptomatic Plasmodium carriage and rainfall were plotted. Numbers of clinical malaria episodes and asymptomatic parasite carriers were mapped using Quantum Geographic Information System (QGIS). Landscape features of Bandiagara were obtained from Google earth. Cluste...
Vaccine, 2020
To prevent premature dismissal of promising vaccine programs, it is critical to determine if lack... more To prevent premature dismissal of promising vaccine programs, it is critical to determine if lack of efficacy in the field is due to allele specific-efficacy, rather than to the lack of immunogenicity of the candidate antigen. Here we use samples collected during a field trial of the AMA1-based FMP2.1/AS02 A malaria vaccine, which incorporates the AMA1 variant encoded by the reference Plasmodium falciparum 3D7 strain, to assess the usefulness of epitope-based sieve analysis for the detection of vaccine-induced allele-specific immune responses. The samples used are from volunteers who received the malaria vaccine FMP2.1/AS02 A or a control (rabies vaccine), during a vaccine efficacy field trial, and who later developed malaria. In a previous study, P. falciparum DNA was extracted from all samples, and the ama1 locus amplified and sequenced. Here, a sieve analysis was used to measure T and B-cell escape, and difference in 3D7-like epitopes in the two treatment arms. Overall, no difference was observed in mean amino acid distance to the 3D7 AMA1 variant between sequences from vaccinees and controls in B-cell epitopes. However, we found a significantly greater proportion of 3D7-like T-cell epitopes that map to the AMA1 cluster one loop (c1L) region in the control vs. the vaccinee group (p = 0.02), consistent with allele-specific vaccine efficacy. Interestingly, AMA1 epitopes in infections from vaccinees had higher mean IC50, and consequently lower binding affinity, than epitopes generated from the control group (p = 0.01), suggesting that vaccine-induced selection impacted the immunological profile of the strains that pass through the sieve imposed by the vaccine-induced protection. These findings are consistent with a vaccine-derived sieve effect on the c1L region of AMA1 and suggest that sieve analyses of malaria vaccine trial samples targeted to epitopes identified in silico can help identify protective malaria antigens that may be efficacious if combined in a multivalent vaccine.
Malaria Journal, 2019
Background: A malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) eli... more Background: A malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) elicited strain specific efficacy in Malian children that waned in the second season after vaccination despite sustained AMA1 antibody titers. With the goal of identifying a humoral correlate of vaccine-induced protection, pre-and post-vaccination sera from children vaccinated with the AMA1 vaccine and from a control group that received a rabies vaccine were tested for AMA1-specific immunoglobulin G (IgG) subclasses (IgG1, IgG2, IgG3, and IgG4) and for antibody avidity. Methods: Samples from a previously completed Phase 2 AMA1 vaccine trial in children residing in Mali, West Africa were used to determine AMA1-specific IgG subclass antibody titers and avidity by ELISA. Cox proportional hazards models were used to assess correlation between IgG subclass antibody titers and risk of time to first or only clinical malaria episode and risk of multiple episodes. Asexual P. falciparum parasite density measured for each child as area under the curve were used to assess correlation between IgG subclass antibody titers and parasite burden. Results: AMA1 vaccination did not elicit a change in antibody avidity; however, AMA1 vaccinees had a robust IgG subclass response that persisted over the malaria transmission season. AMA1-specific IgG subclass responses were not associated with decreased risk of subsequent clinical malaria. For the AMA1 vaccine group, IgG3 levels at study day 90 correlated with high parasite burden during days 90-240. In the control group, AMA1-specific IgG subclass rise and persistence over the malaria season was modest and correlated with age. In the control group, titers of several IgG subclasses at days 90 and 240 correlated with parasite burden over the first 90 study days, and IgG3 at day 240 correlated with parasite burden during days 90-240. Conclusions: Neither IgG subclass nor avidity was associated with the modest, strain-specific efficacy elicited by this blood stage malaria vaccine. Although a correlate of protection was not identified, correlations between subclass titers and age, and correlations between IgG subclass titers and parasite burden, defined by area under the curve parasitaemia levels, were observed, which expand knowledge about IgG subclass responses. IgG3, known to have the shortest half-life of the IgG subclasses, might be the most temporally relevant indicator of ongoing malaria exposure when examining antibody responses to AMA1.
Bulletin de la Société de pathologie exotique, 2012
L'épidémiologie de la leishmaniose cutanée (LC) à Leishmania major est peu documentée au Mali. Su... more L'épidémiologie de la leishmaniose cutanée (LC) à Leishmania major est peu documentée au Mali. Suite à un signalement de LC dans le pays dogon, une équipe bioclinique franco-malienne a été mise en place pour une étude de terrain du 16 au 27 janvier 2010. La population de cinq villages a été examinée et une sélection de cas a été effectuée par inspection des lésions cutanées. Des prélèvements cutanés au niveau des lésions et sanguins ont été effectués chez les malades retenus. Le diagnostic a été établi par microscopie, culture, sérologie et biologie moléculaire. Sur 50 patients porteurs de lésions cutanées, 21 ont été suspects de LC et 18 ont pu avoir au moins un prélèvement. Les lésions étaient anciennes, cicatricielles et plus ou moins surinfectées. Frottis cutanés et cultures ont tous été négatifs. La PCR (Leishmania sp.) a été positive pour 12 patients sur 14 (86 %). La sérologie par western blot (WB) a été positive dans 11 cas sur 12 (92 %). Cette investigation met en évidence une présence de la LC dans le cercle de Bandiagara. Pour citer cette revue : Bull. Soc. Pathol. Exot. 105 (2012).
Malaria Journal, 2014
Background: The recent decline in malaria incidence in many African countries has been attributed... more Background: The recent decline in malaria incidence in many African countries has been attributed to the provision of prompt and effective anti-malarial treatment using artemisinin-based combination therapy (ACT) and to the widespread distribution of long-lasting, insecticide-treated bed nets (LLINs). At a malaria vaccine-testing site in Bandiagara, Mali, ACT was introduced in 2004, and LLINs have been distributed free of charge since 2007 to infants after they complete the Expanded Programme of Immunization (EPI) schedule and to pregnant women receiving antenatal care. These strategies may have an impact on malaria incidence. Methods: To document malaria incidence, a cohort of 400 children aged 0 to 14 years was followed for three to four years up to July 2013. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection and anaemia. Clinical disease was measured both actively and passively through continuous availability of primary medical care. Measured outcomes included asymptomatic Plasmodium infection, anaemia and clinical malaria episodes. Results: The incidence rate of clinical malaria varied significantly from June 2009 to July 2013 without a clear downward trend. A sharp seasonality in malaria illness incidence was observed with higher clinical malaria incidence rates during the rainy season. Parasite and anaemia point prevalence also showed seasonal variation with much higher prevalence rates during rainy seasons compared to dry seasons. Conclusions: Despite the scaling up of malaria prevention and treatment, including the widespread use of bed nets, better diagnosis and wider availability of ACT, malaria incidence did not decrease in Bandiagara during the study period.
PLoS ONE, 2013
Background: In 2012, 6.6 million children under age five died worldwide, most from diseases with ... more Background: In 2012, 6.6 million children under age five died worldwide, most from diseases with known means of prevention and treatment. A delivery gap persists between well-validated methods for child survival and equitable, timely access to those methods. We measured early child health care access, morbidity, and mortality over the course of a health system strengthening model intervention in Yirimadjo, Mali. The intervention included Community Health Worker active case finding, user fee removal, infrastructure development, community mobilization, and prevention programming. Methods and Findings: We conducted four household surveys using a cluster-based, population-weighted sampling methodology at baseline and at 12, 24, and 36 months. We defined our outcomes as the percentage of children initiating an effective antimalarial within 24 hours of symptom onset, the percentage of children reported to be febrile within the previous two weeks, and the under-five child mortality rate. We compared prevalence of febrile illness and treatment using chi-square statistics, and estimated and compared under-five mortality rates using Cox proportional hazard regression. There was a statistically significant difference in under-five mortality between the 2008 and 2011 surveys; in 2011, the hazard of under-five mortality in the intervention area was one tenth that of baseline (HR 0.10, p,0.0001). After three years of the intervention, the prevalence of febrile illness among children under five was significantly lower, from 38.2% at baseline to 23.3% in 2011 (PR = 0.61, p = 0.0009). The percentage of children starting an effective antimalarial within 24 hours of symptom onset was nearly twice that reported at baseline (PR = 1.89, p = 0.0195). Conclusions: Community-based health systems strengthening may facilitate early access to prevention and care and may provide a means for improving child survival.
Microscopy, the gold standard for routine malaria diagnosis and rapid diagnosis tests (RDTs) are ... more Microscopy, the gold standard for routine malaria diagnosis and rapid diagnosis tests (RDTs) are required before artemisinin-based combination therapies for malaria case management in Sub-Saharan Africa. Several RDTs have been recommended by World Health Organization (WHO) for use in endemic areas. The aim of this study was to assess the performance of SD Bioline malaria Ag P.f. test and SD Bioline Ag P.f./Pan test, two new RDTs for malaria diagnosis, before their introduction to Mali. A total of 736 patients with clinical malaria were recruited from October to December, 2009 in four field sites of Mali. 75 tests were transported and exposed to usual field conditions before use. The tests were performed on capillary blood. Light microscopic examination of blood smear was performed as the reference. The sensitivity and specificity for detection of Plasmodium falciparum were 99.7% (95% CI, 98.7 to 100) and 73.3% (95% CI, 64.0 to 80.6) for the SD Bioline malaria Ag P.f test, respective...
Le paludisme reste la parasitose avec les taux de morbidite et mortalite les plus eleves et son i... more Le paludisme reste la parasitose avec les taux de morbidite et mortalite les plus eleves et son impact socioeconomique constitue un frein au developpement. Il y a eu une coevolution entre l'hote humain, le vecteur et le Plasmodium avec parfois des adaptations specifiques de resistance. Cela s'est traduit aujourd'hui par la resistance du Plasmodium aux produits antipaludiques et des difficultes de developpement de vaccin efficace. L'exploration de nouveaux axes de recherche s'avere donc pertinent pour la comprehension de certaines adaptations pouvant jouer un role dans la susceptibilite au paludisme. Des differences de susceptibilites au paludisme ont ete decrites chez les Peulh et Dogons symatriques au Mali. La plupart des etudes faites pour comprendre cette difference de susceptibilite ont porte sur l'immunite. Dans ce travail, nous avons fait une approche novatrice plus globale, en etudiant l'interaction entre l'environnement, le systeme immunitaire...
BackgroundDeclines in malaria incidence attributed to the implementation of control strategies ha... more BackgroundDeclines in malaria incidence attributed to the implementation of control strategies have been reported in many African countries. The declines are often accompanied by a shift in clinical burden to older children. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and Long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared to 1999 despite the use of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention (SMC) has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited the universal bed net coverage and indoor residual spray (IRS) implementation in 2017 and 2018.This study aimed to measure the incidence of malaria in the context of recent scaling-up of control strategies.MethodsA cohort of 300 children aged 6 months to 15 years was followed from Oc...
The American Journal of Tropical Medicine and Hygiene, 2006
Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum ... more Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum surface protein anchor molecules implicated in malaria pathogenesis, are thought to protect against symptomatic malaria. Index cases of severe malaria in Malian children 3 months to 14 years of age were matched by age and residence to uncomplicated malaria and healthy controls. Serum antibodies to GPI (IgM and IgG) were measured at the time of severe malaria and after the malaria transmission season. The mean optical density values for IgM and IgG antibodies were higher in children with severe or uncomplicated malaria compared with healthy controls. Similarly, higher percentages of children with IgM and IgG antibodies to GPI were observed in the severe malaria group compared with matched healthy controls. IgG antibody levels to GPI were highest among children with cerebral malaria and children who died. The IgG antibody levels to GPI peaked during periods of malaria transmission and decreased after malaria transmission ended. A direct correlation between age and parasitemia and IgG antibodies to GPI was observed. In summary, higher levels of IgM and IgG antibodies to GPI in young children were associated with disease severity and were short-lived.
BMJ Global Health, 2019
BackgroundMalaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malari... more BackgroundMalaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malaria is the main pathway to death caused by malaria. A study of factors associated with protection against severe malaria is best achieved using a case-control design. However, these studies are affected by the quality and appropriateness of the choice of controls that may introduce important bias in study design and definitively alter the conclusions from the studies. It is of paramount importance that the presence or absence of an episode of severe malaria in the history of the controls is ascertained. In settings with reliable medical data this is easily tracked back from hospital records. In settings like Bandiagara, with weak health care systems, a dedicated approach is needed to track history of severe malaria. We used an adapted verbal autopsy questionnaire to identify presence of cerebral malaria in the history of controls in a case-control study of severe malaria in Bandiagara.We h...
The American journal of tropical medicine and hygiene, Jan 30, 2017
In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to... more In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 20...
Genome medicine, Mar 28, 2017
Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protei... more Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40-60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates. We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data. Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria path...
![Research paper thumbnail of Phase 1 randomized controlled trial to evaluate the safety and immunogenicity of recombinant Pichia pastoris-expressed Plasmodium falciparum apical membrane antigen 1 (PfAMA1-FVO [25-545]) in healthy Malian adults in Bandiagara](https://attachments.academia-assets.com/105769457/thumbnails/1.jpg)
](Malaria Journal, 2016
Background: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel ® was assessed in... more Background: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel ® was assessed in malariaexperienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastorisexpressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel ® , the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin. Methods: A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed. Results: Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group.
International Journal of Infectious Diseases, 2016
Background: Pneumocystis pneumonia (PCP) is one of the most devastating fungal diseases in patien... more Background: Pneumocystis pneumonia (PCP) is one of the most devastating fungal diseases in patients with impaired immunity. Effective antiviral therapies have reduced the burden of PCP among AIDS patients, but an increase in the prevalence of this disease among persons receiving immunosuppressive therapies has been reported. Methods: We retrospectively reviewed HIV and non-HIV PCP patients diagnosed in our department during a nine year period. Data were collected from the local database completed during the diagnosis procedure. For each patient, demographic, clinical, radiological, biological and therapeutic data were analyzed. Results: A total of 21,274 bronchoalveolar samples were received from patients suspected of pneumocystosis during the study period, leading to a discharge diagnosis of PCP for 604 patients (143 HIV-positive and 461 HIV-negative). The ratio of non-HIV versus HIV patients presenting PCP increased from 1.7 to 5.6 during the study period. The mortality rate at day 14 was 16%, occurring mostly in non-HIV patients (20.6% compared to 1.4%, P < 0.0001), while non-HIV patients were less symptomatic at diagnosis than AIDS patients. Conclusions: This study presents one of the higher number of HIV and non-HIV patients presenting with PCP in a single center. Pneumocystosis is now a crucial health challenge for patients receiving immunosuppressive therapy, with a high mortality rate. This study highlights the need for international guidelines for prophylaxis of PCP in non-HIV patients.
Parasite, 2016
There are growing data supporting the differences in susceptibility to malaria described between ... more There are growing data supporting the differences in susceptibility to malaria described between sympatric populations with different lifestyles. Evidence has also been growing for some time that nutritional status and the host's metabolism are part of the complex mechanisms underlying these differences. The role of dietary advanced glycation end-products (AGEs) in the modulation of immune responses (innate and adaptive responses) and chronic oxidative stress has been established. But less is known about AGE implication in naturally acquired immunity and susceptibility to malaria. Since inflammatory immune responses and oxidative events have been demonstrated as the hallmark of malaria infection, it seems crucial to investigate the role of AGE in susceptibility or resistance to malaria. This review provides new insight into the relationship between nutrition, metabolic disorders, and infections, and how this may influence the mechanisms of susceptibility or resistance to malaria in endemic areas.
The Journal of infectious diseases, Jan 27, 2015
Hemoglobin C trait, like Hemoglobin S trait, protects against severe malaria in children, but it... more Hemoglobin C trait, like Hemoglobin S trait, protects against severe malaria in children, but it is unclear whether Hemoglobin C trait also protects against uncomplicated malaria. We hypothesized that Malian children with Hemoglobin C trait would have a lower risk of clinical malaria than children with Hemoglobin AA. Three hundred children aged 0-6 years were enrolled in a cohort study of malaria incidence in Bandiagara, Mali with continuous passive and monthly active follow-up from June 2009 to June 2010. Compared to Hemoglobin AA children (n=242), hemoglobin AC children (n=39) had a longer time to first clinical malaria episode (hazard ratio: 0.19, P=.001; 364 median malaria-free days versus 181 days), fewer episodes of clinical malaria, and a lower cumulative parasite burden. Similarly, Hemoglobin AS children (n=14) had a longer time to first clinical malaria episode than Hemoglobin AA children (hazard ratio: 0.15, P=.015; 364 median malaria-free days versus 181 days), but exp...
International Journal of Ethics Education
Background: Despite an increase in health research conducted in Africa, there are still inadequat... more Background: Despite an increase in health research conducted in Africa, there are still inadequate human resources with research ethics training and lack of local long-term training opportunities in research ethics. A research ethics training program named United States-Mali Research Ethics Training Program (US-Mali RETP) was established through a partnership between the George Washington University Milken Institute School of Public Health (GWSPH), USA and University of Sciences, Techniques & Technologies of Bamako (USTTB), to address the critical need for improved bioethics training, leadership, and policy in Mali. Methods: The aims of the capacity building programme are achieved by leveraging US and Africa-based expertise to strengthen research ethics education and capacity through: (1) intensive faculty development to design ethics training curricula; (2) development of a research ethics specialization within the existing Masters of Public Health program (MPH); and (3) establishi...
International Journal of Molecular Sciences, 2021
Background: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy t... more 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 transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genotypes that have been associated with drug resistance. Methods: A 28-day follow-up efficacy trial of artemether-lumefantrine was conducted in patients aged 6 months and older suffering from uncomplicated falciparum malaria in four different Malian areas during the 2009 malaria transmission season. The polymorphic genetic markers MSP2, MSP1, and Ca1 were used to distinguish between recrudescence and reinfection. Reinfection and recrudescence were then grouped as recurrent infections and analyzed together by PCR-restriction fragment length polymorphism (RFLP) to identify candid...
mSystems, 2021
Malaria parasites display antigens on the surface of infected red blood cells in the human host t... more Malaria parasites display antigens on the surface of infected red blood cells in the human host that facilitate attachment to blood vessels, contributing to the severity of infection. These antigens are highly variable, allowing the parasite to evade the immune system.
BackgroundEvaluation of local transmission epidemiology to characterize malaria risk is essential... more BackgroundEvaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) has been a major asset to this approach. This study aimed to characterize the local spatio-temporal pattern of malaria infection and clinical disease after implementation of Seasonal Malaria Chemoprevention (SMC) and Indoor Residual Spraying (IRS) in Bandiagara, a Malian town.MethodsFrom October 2017 to December 2018, an active and passive surveillance system was established in a cohort study of three hundred children aged from 6 months to 15 years old. Weekly time-series of clinical malaria and monthly time-series of asymptomatic Plasmodium carriage and rainfall were plotted. Numbers of clinical malaria episodes and asymptomatic parasite carriers were mapped using Quantum Geographic Information System (QGIS). Landscape features of Bandiagara were obtained from Google earth. Cluste...
Vaccine, 2020
To prevent premature dismissal of promising vaccine programs, it is critical to determine if lack... more To prevent premature dismissal of promising vaccine programs, it is critical to determine if lack of efficacy in the field is due to allele specific-efficacy, rather than to the lack of immunogenicity of the candidate antigen. Here we use samples collected during a field trial of the AMA1-based FMP2.1/AS02 A malaria vaccine, which incorporates the AMA1 variant encoded by the reference Plasmodium falciparum 3D7 strain, to assess the usefulness of epitope-based sieve analysis for the detection of vaccine-induced allele-specific immune responses. The samples used are from volunteers who received the malaria vaccine FMP2.1/AS02 A or a control (rabies vaccine), during a vaccine efficacy field trial, and who later developed malaria. In a previous study, P. falciparum DNA was extracted from all samples, and the ama1 locus amplified and sequenced. Here, a sieve analysis was used to measure T and B-cell escape, and difference in 3D7-like epitopes in the two treatment arms. Overall, no difference was observed in mean amino acid distance to the 3D7 AMA1 variant between sequences from vaccinees and controls in B-cell epitopes. However, we found a significantly greater proportion of 3D7-like T-cell epitopes that map to the AMA1 cluster one loop (c1L) region in the control vs. the vaccinee group (p = 0.02), consistent with allele-specific vaccine efficacy. Interestingly, AMA1 epitopes in infections from vaccinees had higher mean IC50, and consequently lower binding affinity, than epitopes generated from the control group (p = 0.01), suggesting that vaccine-induced selection impacted the immunological profile of the strains that pass through the sieve imposed by the vaccine-induced protection. These findings are consistent with a vaccine-derived sieve effect on the c1L region of AMA1 and suggest that sieve analyses of malaria vaccine trial samples targeted to epitopes identified in silico can help identify protective malaria antigens that may be efficacious if combined in a multivalent vaccine.
Malaria Journal, 2019
Background: A malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) eli... more Background: A malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) elicited strain specific efficacy in Malian children that waned in the second season after vaccination despite sustained AMA1 antibody titers. With the goal of identifying a humoral correlate of vaccine-induced protection, pre-and post-vaccination sera from children vaccinated with the AMA1 vaccine and from a control group that received a rabies vaccine were tested for AMA1-specific immunoglobulin G (IgG) subclasses (IgG1, IgG2, IgG3, and IgG4) and for antibody avidity. Methods: Samples from a previously completed Phase 2 AMA1 vaccine trial in children residing in Mali, West Africa were used to determine AMA1-specific IgG subclass antibody titers and avidity by ELISA. Cox proportional hazards models were used to assess correlation between IgG subclass antibody titers and risk of time to first or only clinical malaria episode and risk of multiple episodes. Asexual P. falciparum parasite density measured for each child as area under the curve were used to assess correlation between IgG subclass antibody titers and parasite burden. Results: AMA1 vaccination did not elicit a change in antibody avidity; however, AMA1 vaccinees had a robust IgG subclass response that persisted over the malaria transmission season. AMA1-specific IgG subclass responses were not associated with decreased risk of subsequent clinical malaria. For the AMA1 vaccine group, IgG3 levels at study day 90 correlated with high parasite burden during days 90-240. In the control group, AMA1-specific IgG subclass rise and persistence over the malaria season was modest and correlated with age. In the control group, titers of several IgG subclasses at days 90 and 240 correlated with parasite burden over the first 90 study days, and IgG3 at day 240 correlated with parasite burden during days 90-240. Conclusions: Neither IgG subclass nor avidity was associated with the modest, strain-specific efficacy elicited by this blood stage malaria vaccine. Although a correlate of protection was not identified, correlations between subclass titers and age, and correlations between IgG subclass titers and parasite burden, defined by area under the curve parasitaemia levels, were observed, which expand knowledge about IgG subclass responses. IgG3, known to have the shortest half-life of the IgG subclasses, might be the most temporally relevant indicator of ongoing malaria exposure when examining antibody responses to AMA1.
Bulletin de la Société de pathologie exotique, 2012
L'épidémiologie de la leishmaniose cutanée (LC) à Leishmania major est peu documentée au Mali. Su... more L'épidémiologie de la leishmaniose cutanée (LC) à Leishmania major est peu documentée au Mali. Suite à un signalement de LC dans le pays dogon, une équipe bioclinique franco-malienne a été mise en place pour une étude de terrain du 16 au 27 janvier 2010. La population de cinq villages a été examinée et une sélection de cas a été effectuée par inspection des lésions cutanées. Des prélèvements cutanés au niveau des lésions et sanguins ont été effectués chez les malades retenus. Le diagnostic a été établi par microscopie, culture, sérologie et biologie moléculaire. Sur 50 patients porteurs de lésions cutanées, 21 ont été suspects de LC et 18 ont pu avoir au moins un prélèvement. Les lésions étaient anciennes, cicatricielles et plus ou moins surinfectées. Frottis cutanés et cultures ont tous été négatifs. La PCR (Leishmania sp.) a été positive pour 12 patients sur 14 (86 %). La sérologie par western blot (WB) a été positive dans 11 cas sur 12 (92 %). Cette investigation met en évidence une présence de la LC dans le cercle de Bandiagara. Pour citer cette revue : Bull. Soc. Pathol. Exot. 105 (2012).
Malaria Journal, 2014
Background: The recent decline in malaria incidence in many African countries has been attributed... more Background: The recent decline in malaria incidence in many African countries has been attributed to the provision of prompt and effective anti-malarial treatment using artemisinin-based combination therapy (ACT) and to the widespread distribution of long-lasting, insecticide-treated bed nets (LLINs). At a malaria vaccine-testing site in Bandiagara, Mali, ACT was introduced in 2004, and LLINs have been distributed free of charge since 2007 to infants after they complete the Expanded Programme of Immunization (EPI) schedule and to pregnant women receiving antenatal care. These strategies may have an impact on malaria incidence. Methods: To document malaria incidence, a cohort of 400 children aged 0 to 14 years was followed for three to four years up to July 2013. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection and anaemia. Clinical disease was measured both actively and passively through continuous availability of primary medical care. Measured outcomes included asymptomatic Plasmodium infection, anaemia and clinical malaria episodes. Results: The incidence rate of clinical malaria varied significantly from June 2009 to July 2013 without a clear downward trend. A sharp seasonality in malaria illness incidence was observed with higher clinical malaria incidence rates during the rainy season. Parasite and anaemia point prevalence also showed seasonal variation with much higher prevalence rates during rainy seasons compared to dry seasons. Conclusions: Despite the scaling up of malaria prevention and treatment, including the widespread use of bed nets, better diagnosis and wider availability of ACT, malaria incidence did not decrease in Bandiagara during the study period.
PLoS ONE, 2013
Background: In 2012, 6.6 million children under age five died worldwide, most from diseases with ... more Background: In 2012, 6.6 million children under age five died worldwide, most from diseases with known means of prevention and treatment. A delivery gap persists between well-validated methods for child survival and equitable, timely access to those methods. We measured early child health care access, morbidity, and mortality over the course of a health system strengthening model intervention in Yirimadjo, Mali. The intervention included Community Health Worker active case finding, user fee removal, infrastructure development, community mobilization, and prevention programming. Methods and Findings: We conducted four household surveys using a cluster-based, population-weighted sampling methodology at baseline and at 12, 24, and 36 months. We defined our outcomes as the percentage of children initiating an effective antimalarial within 24 hours of symptom onset, the percentage of children reported to be febrile within the previous two weeks, and the under-five child mortality rate. We compared prevalence of febrile illness and treatment using chi-square statistics, and estimated and compared under-five mortality rates using Cox proportional hazard regression. There was a statistically significant difference in under-five mortality between the 2008 and 2011 surveys; in 2011, the hazard of under-five mortality in the intervention area was one tenth that of baseline (HR 0.10, p,0.0001). After three years of the intervention, the prevalence of febrile illness among children under five was significantly lower, from 38.2% at baseline to 23.3% in 2011 (PR = 0.61, p = 0.0009). The percentage of children starting an effective antimalarial within 24 hours of symptom onset was nearly twice that reported at baseline (PR = 1.89, p = 0.0195). Conclusions: Community-based health systems strengthening may facilitate early access to prevention and care and may provide a means for improving child survival.
Microscopy, the gold standard for routine malaria diagnosis and rapid diagnosis tests (RDTs) are ... more Microscopy, the gold standard for routine malaria diagnosis and rapid diagnosis tests (RDTs) are required before artemisinin-based combination therapies for malaria case management in Sub-Saharan Africa. Several RDTs have been recommended by World Health Organization (WHO) for use in endemic areas. The aim of this study was to assess the performance of SD Bioline malaria Ag P.f. test and SD Bioline Ag P.f./Pan test, two new RDTs for malaria diagnosis, before their introduction to Mali. A total of 736 patients with clinical malaria were recruited from October to December, 2009 in four field sites of Mali. 75 tests were transported and exposed to usual field conditions before use. The tests were performed on capillary blood. Light microscopic examination of blood smear was performed as the reference. The sensitivity and specificity for detection of Plasmodium falciparum were 99.7% (95% CI, 98.7 to 100) and 73.3% (95% CI, 64.0 to 80.6) for the SD Bioline malaria Ag P.f test, respective...
Le paludisme reste la parasitose avec les taux de morbidite et mortalite les plus eleves et son i... more Le paludisme reste la parasitose avec les taux de morbidite et mortalite les plus eleves et son impact socioeconomique constitue un frein au developpement. Il y a eu une coevolution entre l'hote humain, le vecteur et le Plasmodium avec parfois des adaptations specifiques de resistance. Cela s'est traduit aujourd'hui par la resistance du Plasmodium aux produits antipaludiques et des difficultes de developpement de vaccin efficace. L'exploration de nouveaux axes de recherche s'avere donc pertinent pour la comprehension de certaines adaptations pouvant jouer un role dans la susceptibilite au paludisme. Des differences de susceptibilites au paludisme ont ete decrites chez les Peulh et Dogons symatriques au Mali. La plupart des etudes faites pour comprendre cette difference de susceptibilite ont porte sur l'immunite. Dans ce travail, nous avons fait une approche novatrice plus globale, en etudiant l'interaction entre l'environnement, le systeme immunitaire...
BackgroundDeclines in malaria incidence attributed to the implementation of control strategies ha... more BackgroundDeclines in malaria incidence attributed to the implementation of control strategies have been reported in many African countries. The declines are often accompanied by a shift in clinical burden to older children. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and Long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared to 1999 despite the use of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention (SMC) has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited the universal bed net coverage and indoor residual spray (IRS) implementation in 2017 and 2018.This study aimed to measure the incidence of malaria in the context of recent scaling-up of control strategies.MethodsA cohort of 300 children aged 6 months to 15 years was followed from Oc...
The American Journal of Tropical Medicine and Hygiene, 2006
Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum ... more Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum surface protein anchor molecules implicated in malaria pathogenesis, are thought to protect against symptomatic malaria. Index cases of severe malaria in Malian children 3 months to 14 years of age were matched by age and residence to uncomplicated malaria and healthy controls. Serum antibodies to GPI (IgM and IgG) were measured at the time of severe malaria and after the malaria transmission season. The mean optical density values for IgM and IgG antibodies were higher in children with severe or uncomplicated malaria compared with healthy controls. Similarly, higher percentages of children with IgM and IgG antibodies to GPI were observed in the severe malaria group compared with matched healthy controls. IgG antibody levels to GPI were highest among children with cerebral malaria and children who died. The IgG antibody levels to GPI peaked during periods of malaria transmission and decreased after malaria transmission ended. A direct correlation between age and parasitemia and IgG antibodies to GPI was observed. In summary, higher levels of IgM and IgG antibodies to GPI in young children were associated with disease severity and were short-lived.
BMJ Global Health, 2019
BackgroundMalaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malari... more BackgroundMalaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malaria is the main pathway to death caused by malaria. A study of factors associated with protection against severe malaria is best achieved using a case-control design. However, these studies are affected by the quality and appropriateness of the choice of controls that may introduce important bias in study design and definitively alter the conclusions from the studies. It is of paramount importance that the presence or absence of an episode of severe malaria in the history of the controls is ascertained. In settings with reliable medical data this is easily tracked back from hospital records. In settings like Bandiagara, with weak health care systems, a dedicated approach is needed to track history of severe malaria. We used an adapted verbal autopsy questionnaire to identify presence of cerebral malaria in the history of controls in a case-control study of severe malaria in Bandiagara.We h...
The American journal of tropical medicine and hygiene, Jan 30, 2017
In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to... more In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 20...
Genome medicine, Mar 28, 2017
Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protei... more Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40-60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates. We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data. Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria path...
Malaria Journal, 2016
Background: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel ® was assessed in... more Background: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel ® was assessed in malariaexperienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastorisexpressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel ® , the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin. Methods: A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed. Results: Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group.
International Journal of Infectious Diseases, 2016
Background: Pneumocystis pneumonia (PCP) is one of the most devastating fungal diseases in patien... more Background: Pneumocystis pneumonia (PCP) is one of the most devastating fungal diseases in patients with impaired immunity. Effective antiviral therapies have reduced the burden of PCP among AIDS patients, but an increase in the prevalence of this disease among persons receiving immunosuppressive therapies has been reported. Methods: We retrospectively reviewed HIV and non-HIV PCP patients diagnosed in our department during a nine year period. Data were collected from the local database completed during the diagnosis procedure. For each patient, demographic, clinical, radiological, biological and therapeutic data were analyzed. Results: A total of 21,274 bronchoalveolar samples were received from patients suspected of pneumocystosis during the study period, leading to a discharge diagnosis of PCP for 604 patients (143 HIV-positive and 461 HIV-negative). The ratio of non-HIV versus HIV patients presenting PCP increased from 1.7 to 5.6 during the study period. The mortality rate at day 14 was 16%, occurring mostly in non-HIV patients (20.6% compared to 1.4%, P < 0.0001), while non-HIV patients were less symptomatic at diagnosis than AIDS patients. Conclusions: This study presents one of the higher number of HIV and non-HIV patients presenting with PCP in a single center. Pneumocystosis is now a crucial health challenge for patients receiving immunosuppressive therapy, with a high mortality rate. This study highlights the need for international guidelines for prophylaxis of PCP in non-HIV patients.
Parasite, 2016
There are growing data supporting the differences in susceptibility to malaria described between ... more There are growing data supporting the differences in susceptibility to malaria described between sympatric populations with different lifestyles. Evidence has also been growing for some time that nutritional status and the host's metabolism are part of the complex mechanisms underlying these differences. The role of dietary advanced glycation end-products (AGEs) in the modulation of immune responses (innate and adaptive responses) and chronic oxidative stress has been established. But less is known about AGE implication in naturally acquired immunity and susceptibility to malaria. Since inflammatory immune responses and oxidative events have been demonstrated as the hallmark of malaria infection, it seems crucial to investigate the role of AGE in susceptibility or resistance to malaria. This review provides new insight into the relationship between nutrition, metabolic disorders, and infections, and how this may influence the mechanisms of susceptibility or resistance to malaria in endemic areas.
The Journal of infectious diseases, Jan 27, 2015
Hemoglobin C trait, like Hemoglobin S trait, protects against severe malaria in children, but it... more Hemoglobin C trait, like Hemoglobin S trait, protects against severe malaria in children, but it is unclear whether Hemoglobin C trait also protects against uncomplicated malaria. We hypothesized that Malian children with Hemoglobin C trait would have a lower risk of clinical malaria than children with Hemoglobin AA. Three hundred children aged 0-6 years were enrolled in a cohort study of malaria incidence in Bandiagara, Mali with continuous passive and monthly active follow-up from June 2009 to June 2010. Compared to Hemoglobin AA children (n=242), hemoglobin AC children (n=39) had a longer time to first clinical malaria episode (hazard ratio: 0.19, P=.001; 364 median malaria-free days versus 181 days), fewer episodes of clinical malaria, and a lower cumulative parasite burden. Similarly, Hemoglobin AS children (n=14) had a longer time to first clinical malaria episode than Hemoglobin AA children (hazard ratio: 0.15, P=.015; 364 median malaria-free days versus 181 days), but exp...