High Frequency of CYP2C19*3 Heterozygotes Among Patients Under Clopidogrel Treatment in Ouagadougou, Burkina Faso.

<b>Background and Objective:</b> Despite its widespread use in cardiology, patient's response to clopidogrel exhibits significant interindividual variability, often leading to persistent thromboembolic complications. The hepatic Cytochrome P450 2C19 (CYP2C19) superfamily plays a pivotal role in clopidogrel's conversion to its active form and CYP2C19 polymorphisms significantly contribute to this variability. This study aimed to evaluate the prevalence and impact of the CYP2C19 rs4986893 polymorphism on clopidogrel treatment response. <b>Materials and Methods:</b> Seventy-three patients with Cardiovascular Diseases (CVD) undergoing clopidogrel antiplatelet therapy for a minimum of six months were recruited from Centre Hospitalier Universitaire Yalgado Ouédraogo (CHU-YO). Sociodemographic data were collected and DNA was extracted from blood samples for CYP2C19 rs4986893 genotyping using PCR-RFLP. <b>Results:</b> The patient's mean age was 62.56±13.45 years, ranging from 23 to 94 years, with a male-to-female sex ratio of 1.28. Most patients came from the informal sector, primarily of Mossi ethnicity and residing in Ouagadougou. Acute coronary syndromes (ACS) and hypertension were the predominant reasons for consultation, with clopidogrel showing efficacy in 97.3% of cases. While 72.6% had no family history of CVD, hypertension was prevalent among those with familial cardiovascular conditions. Genetic analysis revealed a 65.8% frequency of heterozygotes CYP2C19*1/*3, with no mutant homozygotes CYP2C19*3/*3 detected. The results of the present study underscore a high prevalence of heterozygotes CYP2C19*1/*3 among patients with cardiovascular diseases. <b>Conclusion:</b> This intermediate metabolic phenotype, along with a good response to clopidogrel, suggests that CYP2C19*1/*3 genotype promotes a favourable response to clopidogrel therapy.

Indole-N-Linked Hydroperoxyl Adduct of Protein-Derived Cofactor Modulating Catalase-Peroxidase Functions.

Bifunctional catalase-peroxidase (KatG) features a posttranslational methionine-tyrosine-tryptophan (MYW) crosslinked cofactor crucial for its catalase function, enabling pathogens to neutralize hydrogen peroxide during infection. We discovered the presence of indole nitrogen-linked hydroperoxyl adduct (MYW-OOH) in Mycobacterium tuberculosis KatG in the solution state under ambient conditions, suggesting its natural occurrence. By isolating predominantly MYW-OOH-containing KatG protein, we investigated the chemical stability and functional impact of MYW-OOH. We discovered that MYW-OOH inhibits catalase activity, presenting a unique temporary lock. Exposure to peroxide or increased temperature removes the hydroperoxyl adduct from the protein cofactor, converting MYW-OOH to MYW and restoring the detoxifying ability of the enzyme against hydrogen peroxide. Thus, the N-linked hydroperoxyl group is releasable. KatG with MYW-OOH represents a catalase dormant, but primed, state of the enzyme. These findings provide insight into chemical strategies targeting the bifunctional enzyme KatG in pathogens, highlighting the role of N-linked hydroperoxyl modifications in enzymatic function.

High Schistosoma mansoni Co-Infection in Tuberculosis Patients with or without Human Immunodeficiency Virus: A Prospective Cohort Study.

Background People with Latent tuberculosis infection (LTBI) remain the reservoir of tuberculosis. One-third to 1/4 of the world's population is infected. Its reactivation is due to factors that disrupt the host's immune response. Recent findings showed that Schistosoma mansoni coinfection leads to a Th2/Th1 profile which results in an immune modulation that favors the escape of the Mycobacteria. Schistosoma mansoni may contribute to TB incidence in endemic regions. We aimed to investigate the coinfection rate and patient outcomes. Methods A prospective cohort study was conducted between 2020-2022 at University Clinical Research Center (UCRC), including culture-confirmed active pulmonary TB patients and tested for Schistosoma mansoni in stools using Kato-Katz Technique. After descriptive analysis a logistic regression was performed to determine risk factors associated with TB and Schistosoma mansoni co-infection. Results Data of 174 tuberculosis-confirmed patients, Kato-Katz tested were analyzed. Males represented 62.6%, mean age was 34.9 ± 13.8 years, 29.9% were smokers, alcohol consumption 13.8%, TB contact history 26.4%, HIV coinfection 11.5%, diabetes 6.3%, undernourished 55.7%. Schistosoma mansoni prevalence was 28.7%. The co-infection was associated with less lung cavitation [aOR = 0.24 [95% CI (0.06-0.85), p = 0.028], unfavorable treatment result [aOR = 2.95 (1.23-7.08), p = 0.015] and death [aOR = 3.43 (1.12-10.58), p = 0.032]. Conclusions Despite Kato-Katz's low sensitivity, Schistosoma mansoni coinfection was found in one-third of the TB patients; 2.5-fold higher than that of HIV. The coinfection was associated with poor treatment results and death.

Whole-genome sequencing of major malaria vectors reveals the evolution of new insecticide resistance variants in a longitudinal study in Burkina Faso.

BACKGROUND: Intensive deployment of insecticide based malaria vector control tools resulted in the rapid evolution of phenotypes resistant to these chemicals. Understanding this process at the genomic level is important for the deployment of successful vector control interventions. Therefore, longitudinal sampling followed by whole genome sequencing (WGS) is necessary to understand how these evolutionary processes evolve over time. This study investigated the change in genetic structure and the evolution of the insecticide resistance variants in natural populations of Anopheles gambiae over time and space from 2012 to 2017 in Burkina Faso. METHODS: New genomic data have been generated from An. gambiae mosquitoes collected from three villages in the western part of Burkina Faso between 2012 and 2017. The samples were whole-genome sequenced and the data used in the An. gambiae 1000 genomes (Ag1000G) project as part of the Vector Observatory. Genomic data were analysed using the analysis pipeline previously designed by the Ag1000G project. RESULTS: The results showed similar and consistent nucleotide diversity and negative Tajima's D between An. gambiae sensu stricto (s.s.) and Anopheles coluzzii. Principal component analysis (PCA) and the fixation index (FST) showed a clear genetic structure in the An. gambiae sensu lato (s.l.) species. Genome-wide FST and H12 scans identified genomic regions under divergent selection that may have implications in the adaptation to ecological changes. Novel voltage-gated sodium channel pyrethroid resistance target-site alleles (V402L, I1527T) were identified at increasing frequencies alongside the established alleles (Vgsc-L995F, Vgsc-L995S and N1570Y) within the An. gambiae s.l. POPULATIONS: Organophosphate metabolic resistance markers were also identified, at increasing frequencies, within the An. gambiae s.s. populations from 2012 to 2017, including the SNP Ace1-G280S and its associated duplication. Variants simultaneously identified in the same vector populations raise concerns about the long-term efficacy of new generation bed nets and the recently organophosphate pirimiphos-methyl indoor residual spraying in Burkina Faso. CONCLUSION: These findings highlighted the benefit of genomic surveillance of malaria vectors for the detection of new insecticide resistance variants, the monitoring of the existing resistance variants, and also to get insights into the evolutionary processes driving insecticide resistance.

Implementing a pragmatic randomised controlled trial in a humanitarian setting: lessons learned from the TISA trial.

INTRODUCTION: High-quality evidence is crucial for guiding effective humanitarian responses, yet conducting rigorous research, particularly randomised controlled trials, in humanitarian crises remains challenging. The TISA ("traitement intégré de la sous-nutrition aiguë") trial aimed to evaluate the impact of a Water, Sanitation and Hygiene (WASH) intervention on the standard national treatment of uncomplicated Severe Acute Malnutrition (SAM) in children aged 6-59 months. Implemented in two northern Senegalese regions from December 22, 2021, to February 20, 2023, the trial faced numerous challenges, which this paper explores along with the lessons learned. METHODS: The study utilised trial documentation, including field reports, meeting minutes, training plans, operational monitoring data and funding proposals, to retrace the trial timeline, identify challenges and outline implemented solutions. Contributions from all TISA key staff-current and former, field-based and headquarters-were essential for collecting and interpreting information. Challenges were categorised as internal (within the TISA consortium) or external (broader contextual issues). RESULTS: The TISA trial, executed by a consortium of academic, operational, and community stakeholders, enrolled over 2000 children with uncomplicated SAM across 86 treatment posts in a 28,000 km2 area. The control group received standard outpatient SAM care, while the intervention group also received a WASH kit and hygiene promotion. Initially planned to start in April 2019 for 12 months, the trial faced a 30-month delay and was extended to 27 months due to challenges like the COVID-19 pandemic, national strikes, health system integration issues and weather-related disruptions. Internal challenges included logistics, staffing, data management, funding and aligning diverse stakeholder priorities. DISCUSSION AND CONCLUSION: Despite these obstacles, the trial concluded successfully, underscoring the importance of tailored monitoring, open communication, transparency and community involvement. Producing high-quality evidence in humanitarian contexts demands extensive preparation and strong coordination among local and international researchers, practitioners, communities, decision-makers and funders from the study's inception. TRIAL REGISTRATION: Clinicaltrials.gov NCT04667767 .

Determinants of stunting in children aged 0-59 months in three regions of Burkina Faso.

The Sahel is a region particularly characterized by undernutrition in several forms. In Burkina Faso, where several interventions have been carried out across the past several years, the nutritional situation of children under five years of age is still characterized by persistent stunting in the Est, Sahel, and Cascades regions. This study aims to understand the factors associated with the high prevalence of chronic malnutrition in these regions. National nutrition survey data as well as data from the Ministry of Water and Sanitation were used for bivariate and multivariate statistical analyses to identify factors statistically associated with stunting in children aged 0-59 months who participated in the national nutritional surveys from 2009 to 2019. Around one in ten mothers in all regions had no schooling at all. The improving of IYCF practice has a positive impact on the reduction of the prevalence of chronic malnutrition among children in the Cascades, Est and Sahel regions. In the three target regions, gender and province were significantly associated with stunting. Fever, diarrhea, vitamin A supplementation, household size, and maternal education level were also associated with stunting but only in the Sahel and Cascades regions. Overall, the results of the study show that the fight against stunting must be carried out in a multisectoral approach and target certain provinces particularly because stunting is not uniformly present in all provinces.

Willingness of West African Consumers to Buy Food Produced Using Black Soldier Fly Larvae and Frass.

The use of black soldier fly (BSF) larvae and frass in agriculture can make an important contribution to food and nutrition security. However, it is important to understand whether consumers are willing to consume food products resulting from the use of BSF larvae as animal feed or BSF frass as fertilizer. This study employed the stated preference approach as food products produced using BSF larvae and frass are not currently available on the market. Questionnaires were administered to a total of 4412 consumers in Ghana (1360), Mali (1603), and Niger (1449). The results show that the vast majority of respondents are willing to consume vegetables (88%) produced using BSF frass and meat (87%) produced using animal feed made of BSF larvae. A smaller percentage of respondents are even willing to pay USD 1.32 and USD 1.7 more if the base price of BSF-based products were USD 5 per kg. Age, gender, education, and country positively influenced the respondents' willingness to consume food produced using BSF products. In contrast, neighborhood status, income, and household size are inversely related to the respondents' willingness to pay for and consume these products. Our findings are, therefore, important to scaling up BSF technologies in the region.

Analysis of care-seeking pathways and factors influencing early and appropriate care-seeking for malaria patients in the Republic of Guinea: a cross-sectional study.

BACKGROUND: Malaria is a major public health issue in Guinea and care-seeking behaviour is dominated by self-medication and delayed access to appropriate care. However early and appropriate care-seeking are essential to control and reduce complicate forms and mortality, particularly for the most vulnerable. This study was conducted to analyse the diagnostic pathway, and the factors associated with early and appropriate care-seeking for malaria patients in the Republic of Guinea. METHODS: A cross-sectional study was carried out between December 2022 to March 2023 in nine health districts within health facilities and at community level. The study population was confirmed malaria patients with RDT or microscopy. Kroeger's conceptual framework was used to design the questionnaire. Conventional recourse was defined as using a healthcare facility or community services, early and appropriate care-seeking was defined as within 24 h of symptom onset in a conventional recourse, and care pathway as the sequence of recourses followed by each patient. Sankey alluvial plots were used to represent patients' diagnostic pathways, and logistic regression to identify factors associated with early and appropriate care-seeking. RESULTS: A total of 3300 malaria patients were studied, of which 1632 (49.45%) were female and 1132 (34.30%) were under 5 years of age, with a median age of 23 months. At the time of the survey, 1337 (40.52%), 1423 (43.12%), and 437 (13.85%) of patients were respectively in their first, second and third recourse. A total of 2002 (60.67%) patients had sought care from a conventional recourse as a first line. Of all patients, 1757 (53.25%) had sought care within 24 h, while 28.55% had sought early and appropriate care. In the initial stages of treatment, self-medication was the most common approach, used by 1214 (37.30%). Patients from the health districts of Boffa (Lower Guinea, coastal region) OR = 0.48 95% CI 0.33-0.70, Dabola (Upper Guinea, savanna region) OR = 0.43 95% CI 0.30-0.63 and Labe (Middle Guinea, mountain region) OR = 0.63 CI 95% 0.43-0.91 (p < 0.05) were more likely to delay appropriate care-seeking, when compared to those in Dixinn, (Conakry). However, the under 5-year-old group OR = 1.55 95% CI 1.30-1.85 (p < 0.001) and the availability of a stable monthly household income OR = 4.98 95% CI 3.03, 8.27 (p < 0.001) were positively associated with early and appropriate care seeking. CONCLUSION: A low rate of early and appropriate care-seeking was observed. Patients sought care through multiple means, often resulting in a delay in adequate management. The results show the need to deploy strategies adapted to the needs of communities.

[Characterization of injuries among elite football players during a sports season in Burkina Faso: the 2019-2020 sports season]. / Caractérisation des blessures sur une saison sportive chez des footballeurs d'élite au Burkina Faso: cas de la saison 2019-2020.

Introduction: injuries are a major undesirable event in sportsmen's career and prevention depends on their characteristics. The aim of this study was to determine the characteristics of injuries suffered by elite footballers in Burkina Faso during the 2019-2020 sports season. Methods: we conducted a cross-sectional study among 160 players who were administered a questionnaire. Proportion and χ2 tests were used to calculate frequencies and determine associated factors, respectively. Results: a total of 157 injuries were recorded in 143 players (89.4%). Muscle injuries (45.85%) and sprains (30.6%) were common. The majority of injuries (52%) were of medium severity. The thigh (30%), ankle (26.5%) and knee (18%) were the most affected areas. The frequency of injuries was higher after physical contact than without physical contact with another player (69.5% versus 30.5; p = 0.009), during matches than during training (82% versus 28%; p = 0.003) and during the return leg than the first leg of the championship (58.5% versus 41.5%; p = 0.02). Conclusion: the frequency of injuries suffered by footballers during the 2019-2020 season was high. These injuries were mostly muscular and tendinous, and the lower limbs were mostly affected. They were associated with physical contact, matches and the return phase of the championship. To be effective, preventive measures should take these characteristics into account.

Infection length and host environment influence on Plasmodium falciparum dry season reservoir.

Persistence of malaria parasites in asymptomatic hosts is crucial in areas of seasonally-interrupted transmission, where P. falciparum bridges wet seasons months apart. During the dry season, infected erythrocytes exhibit extended circulation with reduced cytoadherence, increasing the risk of splenic clearance of infected cells and hindering parasitaemia increase. However, what determines parasite persistence for long periods of time remains unknown. Here, we investigated whether seasonality affects plasma composition so that P. falciparum can detect and adjust to changing serological cues; or if alternatively, parasite infection length dictates clinical presentation and persistency. Data from Malian children exposed to alternating ~6-month wet and dry seasons show that plasma composition is unrelated to time of year in non-infected children, and that carrying P. falciparum only minimally affects plasma constitution in asymptomatic hosts. Parasites persisting in the blood of asymptomatic children from the dry into the ensuing wet season rarely if ever appeared to cause malaria in their hosts as seasons changed. In vitro culture in the presence of plasma collected in the dry or the wet seasons did not affect parasite development, replication or host-cell remodelling. The absence of a parasite-encoded sensing mechanism was further supported by the observation of similar features in P. falciparum persisting asymptomatically in the dry season and parasites in age- and sex-matched asymptomatic children in the wet season. Conversely, we show that P. falciparum clones transmitted early in the wet season had lower chance of surviving until the end of the following dry season, contrasting with a higher likelihood of survival of clones transmitted towards the end of the wet season, allowing for the re-initiation of transmission. We propose that the decreased virulence observed in persisting parasites during the dry season is not due to the parasites sensing ability, nor is it linked to a decreased capacity for parasite replication but rather a consequence decreased cytoadhesion associated with infection length.

Continuous flow synthesis and simulation-supported investigation of tunable plasmonic gold patchy nanoparticles.

Plasmonic nanoparticles have intriguing optical properties which make them suitable candidates for sensing or theranostic applications. Anisotropic patchy particles, where metal is locally deposited on the surface of a core particle, exhibit plasmon resonances that can be specifically adjusted for these applications. However, many existing synthesis routes are complex, yield too little material, or provide particles with limited optical tunability. In this work, we present a simple and scalable continuous flow synthesis of gold-on-polystyrene patchy particles with widely adjustable optical properties. By increasing the chloride concentration in the electroless deposition of gold, we slow down the redox reduction kinetics and obtain a dense patch morphology as well as a reduced nucleation rate. The latter is counteracted by introducing a low-level seeding approach where a small number of gold nanocrystals heterocoagulate with the core particles prior to patch growth. Seeding and patch growth are performed in a continuous flow set-up with two T-shaped milli-mixers. The resulting patchy particle samples exhibit a tunable dipolar plasmon peak between 600 nm and 1100 nm. We also investigate the structure-property relationship for our gold patchy particles using finite element method simulations. After identifying a suitable patch shape model, we elucidate the influence of individual geometric parameters on the optical properties and show that the relationship holds true for a large range of patch coverages. Finally, we apply the relationship to explain the time-dependent change in the optical properties of as-synthesized patches by correlating it with the patch shape transformation revealed by electron microscopy.

Coronavirus awareness, prevention, and household hardship survey data for the CHAMPS HDSS network: Data collected between August and September of 2022 from the Bamako HDSS, Mali.

Data were gathered through a collaborative initiative to investigate impacts of the COVID-19 pandemic and related lockdowns on child and maternal health, economic hardships, and access to care for children and pregnant women by the Child Health and Mortality Prevention Surveillance (CHAMPS) Network. The data were gathered in Bamako, the capital city of Mali (population ∼2.9 million) between August and September of 2022 through a Health and Demographic Surveillance System (HDSS). Data collectors used a survey instrument specifically designed to measure household awareness, knowledge, and prevalence of COVID-19, as well as hardships that households experienced since the onset of the pandemic in March of 2020. The data are from two neighborhoods of Bamako, Banconi and Djicoroni; the Health and Demographic Surveillance System (HDSS) operating in these neighborhoods tracks the health of approximately 235,000 inhabitants. The data were collected using a stratified random sample of 454 households.

Predominance of DENV-3 among patients in Ouagadougou, Burkina Faso.

BACKGROUND OBJECTIVES: Dengue is an emerging vector-borne viral disease in tropical and subtropical areas such as Burkina Faso that experienced dengue outbreak in, 2013, 2016, 2017 and more recently in 2023. This study aimed to determine the seroprevalence and dengue serotype in suspected patients in Ouagadougou, Burkina Faso. METHODS: The study was conducted during October and November 2023 and included suspected febrile patients seen at HOSCO and CERBA. Plasma or serum samples were used for the detection of non-structural proteins (NS1) and IgM and IgG antibodies against the dengue virus using SD Bioline Dengue Duo rapid detection kit. Viral RNA was extracted using the QIAamp Viral RNA Mini Kit and dengue serotypes were determined by real-time RT-PCR using the Dengue Real-TM Genotype kit. RESULTS: The study population consisted of 896 patients, including 397 (44.3%) men and 499 (55.7%) women. Dengue seroprevalence was 16.5% (148/896) with 14.1% (126/896) of patients positive for the NS1 antigen, 1.3% (12/896) positive for IgM, and 2.7% (24/896) positive for IgG. Serotyping among 40 out of 45 positive patients revealed 77.5% (31/40) DENV-3, 17.5% (7/40) DENV-1, and 5.0% (2/40) DENV-2. INTERPRETATION CONCLUSION: The present study report a high seroprevalence of dengue virus infection among patients during the months considered as the peak of infection in Burkina Faso. The results revealed a predominance of DENV-3. Continuous surveillance of dengue virus serotypes circulating in Burkina Faso is crucial.

Barriers to Oral PrEP: A Qualitative Study of Female Sex Workers, PrEP Prescribers, Policymakers, and Community Advocates in Morocco.

In 2017, Morocco became the first Arab country to incorporate pre-exposure prophylaxis (PrEP) in its HIV-prevention program. Yet no research has been published on PrEP from Morocco. Although female sex workers are one of the target populations of PrEP in Morocco, their enrollment in PrEP is lower than men who have sex with men. In this study, we conducted 38 semi-structured interviews with female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. We also investigated preferences for daily oral, vaginal ring, and long-acting injectable PrEP. A reflexive thematic analysis revealed seven themes: PrEP stigma; stigmatization and criminalization of sex work; one size doesn't fit all; knowledge and misconceptions about PrEP; economic burden; inconvenience of PrEP pills; and preferred PrEP modalities. This paper discusses the implications of the findings for increasing access and use of PrEP in Morocco.

Factors that Influence Uptake of Oral PrEP among Female Sex Workers One of the most recent scientific advancements in the history of the HIV pandemic was the introduction of pre-exposure prophylaxis (PrEP). However, the uptake of PrEP in the Arab world is low. In this paper we interviewed female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. Several barriers were identified including stigma attached to PrEP, misconceptions about PrEP, and financial burden. Although most female sex workers in our study were interested in using PrEP, the delivery methods of PrEP should be tailored to fit the lifestyle and personal circumstances of potential users.

Use of strips of rapid diagnostic tests as a source of ribonucleic acid for genomic surveillance of viruses: an example of SARS-CoV-2.

BACKGROUND: This study aimed to demonstrate that the genomic material of SARS-CoV-2 can be isolated from strips of COVID-19 rapid diagnostic test cassettes. METHOD: It was a prospective cross-sectional study involving patients admitted to treatment centers and sampling sites in the city of Conakry, Guinea. A total of 121 patients were double sampled, and 9 more patients were tested only for RDT. PCR was conducted according to the protocol of the RunMei kit. Sequencing was performed by using the illumina COVIDSeq protocol. Nine COVID-19 RDTs without nasopharyngeal swabs were in addition tested. RESULT: Among the 130 COVID-19 RDTs, forty-seven were macroscopically positive, whereas seventy-two were positive according to PCR using RDT strip, while among the 121 VTM swabs, sixty-four were positive. Among eighty-three negative COVID-19 RDTs, twenty-seven were positive by PCR using RDT strip with a geometric mean Ct value of 32.49 cycles. Compared to those of PCR using VTM, the sensitivity and specificity of PCR using RDT strip were estimated to be 100% and 85.96%, respectively, with 93.39% test accuracy. Among the fifteen COVID-19 RDT extracts eligible for sequencing, eleven had sequences identical to those obtained via the standard method, with coverage between 75 and 99.6%. CONCLUSION: These results show that COVID-19 RDTs can be used as biological material for the genomic surveillance of SARS-CoV-2.

Hyperimmune malarial splenomegaly in a malaria-endemic area of southwest Burkina Faso: case of Bobo-Dioulasso.

INTRODUCTION: Hyperreactive malarial splenomegaly (HMS) is one of the main causes of massive splenomegaly in malaria-endemic zones. Diagnosis is often challenging in Bobo-Dioulasso. This study aimed to describe the clinical and socio-demographic profile, and the reasons for delay in the diagnosis of HMS cases recorded in the Medicine and Medical Specialties wards of Souro Sanou Teaching hospital. METHODS: A retrospective descriptive study was conducted from August 2022 by focusing on HMS cases diagnosed in the Infectious Diseases and Clinical Hematology wards of Souro Sanou Teaching Hospital. RESULTS: Overall, 65 patients met our inclusion criteria over the 12-year period. Burkinabe nationals and have been residing in Burkina Faso since their birth. 79% (79%) of the patients were seen for medical consultation with the reason for consultation being a voluminous mass in the left hypochondrium. Indigence, self-medication, and lack of information were essential elements in late diagnosis of HMS in Bobo-Dioulasso. All patients were treated with a single tablet of Artemether (80 mg) and Lumefantrine (480 mg) in the morning and evening for 3 days, followed by sulfadoxine-pyrimethamine per week. Nine months later, patients were clinically asymptomatic. CONCLUSION: This study provides a database on hyperreactive malarial splenomegaly (HMS) in the south-west region of Burkina Faso. Rapid and accurate diagnosis of the disease and appropriate use of effective antimalarial drugs would significantly reduce the burden of HMS in Sub-Saharan African countries.

Optimizing type, date, and dose of compost fertilization of organic cotton under climate change in Mali: A modeling study.

Adapting organic farming to climate change is a major issue. Cotton yields in Mali are declining due to deteriorating climatic conditions, soil fertility, and poor management. This study aimed to improve organic cotton yield in Mali in the future climate with the optimal choice of compost type, date, and dose of application. Experimental data collected in 2021 from the Sotuba research station in Mali was used for calibration and evaluation of the crop model DSSAT CSM-CROPGRO-Cotton model using phenology, leaf area index, and seed cotton yield. Climate data from the RCP4.5 and RCP8.5 scenarios of the GFDL-ESM2M model were used for future weather datasets for 2020-2039, 2040-2059, and 2060-2079. The model was able to simulate anthesis and maturity with excellent results, with nRMSE < 4%, and seed cotton yields moderately well, an nRMSE of 26% during calibration and 20.3% in evaluation. The scenario RCP8.5 from 2060 to 2079 gave the best seed cotton yields. Seed cotton yields with RCP4.5 and RCP8.5 were all better with the mid-May application period of small ruminant silo compost at 7.5 t/ha. In such conditions, more than 75% of the cases would produce more than 2000 kg/ha of seed cotton.

Safety and efficacy of PfSPZ Vaccine against malaria in healthy adults and women anticipating pregnancy in Mali: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

BACKGROUND: Plasmodium falciparum parasitaemia during pregnancy causes maternal, fetal, and infant mortality. Poor pregnancy outcomes are related to blood-stage parasite sequestration and the ensuing inflammatory response in the placenta, which decreases over successive pregnancies. A radiation-attenuated, non-replicating, whole-organism vaccine based on P falciparum sporozoites (PfSPZ Vaccine) has shown efficacy at preventing infection in African adults. Here, we aimed to examine vaccine safety and efficacy of the PfSPZ Vaccine in adults and women who anticipated conception. METHODS: Two randomised, double-blind, placebo-controlled trials (phase 1 MLSPZV3 and phase 2 MLSPZV4) were conducted at a clinical research centre in Mali. MLSPZV3 included adults aged 18-35 years and MLSPZV4 included non-pregnant women aged 18-38 years who anticipated conception within a year of enrolment. In MLSPZV3, participants were stratified by village and randomly assigned (2:1) using block randomisation to receive three doses of 9 × 105 PfSPZ Vaccine or saline placebo at weeks 0, 1, and 4 (4-week schedule) or at weeks 0, 8, and 16 (16-week schedule) and a booster dose around 1 year later. In MLSPZV4, women received presumptive artemether-lumefantrine twice per day for 3 days 2 weeks before dose one and were randomly assigned (1:1:1) using block randomisation to receive three doses of 9 × 105 or 1·8 × 106 PfSPZ Vaccine or saline placebo all administered at weeks 0, 1, and 4 (4-week schedule). Participants in both studies received artemether-lumefantrine 2 weeks before dose three and additionally 2 weeks before dose four (booster dose) in MLSPZV3. Investigators and participants were masked to group assignment. The primary outcome, assessed in the as-treated population, was PfSPZ Vaccine safety and tolerability within 7 days after each dose. The secondary outcome, assessed in the modified intention-to-treat population, was vaccine efficacy against P falciparum parasitaemia (defined as the time-to-first positive blood smear) from dose three until the end of transmission season. In exploratory analyses, MLSPZV4 evaluated incidence of maternal obstetric and neonatal outcomes as safety outcomes, and vaccine efficacy against P falciparum parasitaemia during pregnancy (defined as time-to-first positive blood smear post-conception). In MLSPZV4, women were followed at least once a month with human chorionic gonadotropin testing, and those who became pregnant received standard of care (including intermittent presumptive sulfadoxine-pyrimethamine antimalarial drugs after the first trimester) during routine antenatal visits. These studies are registered with ClinicalTrials.gov, NCT03510481 and NCT03989102. FINDINGS: Participants were enrolled for vaccination during the onset of malaria seasons for two sequential studies conducted from 2018 to 2019 for MLSPZV3 and from 2019 to 2021 for MLSPZV4, with follow-up during malaria seasons across 2 years. In MLSPZV3, 478 adults were assessed for eligibility, of whom 220 were enrolled between May 30 and June 12, 2018, and then between Aug 13 and Aug 18, 2018, and 210 received dose one. 66 (96%) of 69 participants who received the 16-week schedule and 68 (97%) of 70 who received the 4-week schedule of the 9 × 105 PfSPZ Vaccine and 70 (99%) of 71 who received saline completed all three doses in year 1. In MLSPZV4, 407 women were assessed for eligibility, of whom 324 were enrolled from July 3 to July 27, 2019, and 320 received dose one of presumptive artemether-lumefantrine. 300 women were randomly assigned with 100 per group (PfSPZ Vaccine 9 × 105, 1·8 × 106, or saline) receiving dose one. First trimester miscarriages were the most commonly reported serious adverse event but occurred at a similar rate across study groups (eight [15%] of 54 with 9 × 105 PfSPZ Vaccine, 12 [21%] of 58 with 1·8 × 106 PfSPZ Vaccine, and five [12%] of 43 with saline). One unrelated maternal death occurred 425 days after the last vaccine dose in the 1·8 × 106 PfSPZ Vaccine group due to peritonitis shortly after childbirth. Most related adverse events reported in MLSPZV3 and MLSPZV4 were mild (grade 1) and frequency of adverse events in the PfSPZ Vaccine groups did not differ from that in the saline group. Two unrelated serious adverse events occurred in MLSPZV3 (one participant had appendicitis in the 9 × 105 PfSPZ Vaccine group and the other in the saline group died due to a road traffic accident). In MLSPZV3, the 9 × 105 PfSPZ Vaccine did not show vaccine efficacy against parasitaemia with the 4-week (27% [95% CI -18 to 55] in year 1 and 42% [-5 to 68] in year 2) and 16-week schedules (16% [-34 to 48] in year 1 and -14% [-95 to 33] in year 2); efficacies were similar or worse against clinical malaria compared with saline. In MLSPZV4, the PfSPZ Vaccine showed significant efficacy against parasitaemia at doses 9 × 105 (41% [15 to 59]; p=0·0069 in year 1 and 61% [36 to 77]; p=0·0011 in year 2) and 1·8 × 106 (54% [34 to 69]; p<0·0001 in year 1 and 45% [13 to 65]; p=0·029 in year 2); and against clinical malaria at doses 9 × 105 (47% [20 to 65]; p=0·0045 in year 1 and 56% [22 to 75]; p=0·0081 in year 2) and 1·8 × 106 (48% [22 to 65]; p=0·0013 in year 1 and 40% [2 to 64]; p=0·069 in year 2). Vaccine efficacy against post-conception P falciparum parasitaemia during first pregnancies that arose in the 2-year follow-up was 57% (14 to 78; p=0·017) in the 9 × 105 PfSPZ Vaccine group versus 49% (3 to 73; p=0·042) in the 1·8 × 106 PfSPZ Vaccine group. Among 55 women who became pregnant within 24 weeks after dose three, vaccine efficacy against parasitaemia was 65% (23 to 84; p=0·0088) with the 9 × 105 PfSPZ Vaccine and 86% (64 to 94; p<0·0001) with the 1·8 × 106 PfSPZ Vaccine. When combined in a post-hoc analysis, women in the PfSPZ Vaccine groups had a non-significantly reduced time-to-first pregnancy after dose one compared with those in the saline group (log-rank test p=0·056). Exploratory maternal obstetric and neonatal outcomes did not differ significantly between vaccine groups and saline. INTERPRETATION: PfSPZ Vaccine was safe and well tolerated in adults in Mali. The 9 × 105 and 1·8 × 106 doses of PfSPZ Vaccine administered as per the 4-week schedule, which incorporated presumptive antimalarial treatment before the first vaccine dose, showed significant efficacy against P falciparum parasitaemia and clinical malaria for two malaria transmission seasons in women of childbearing age and against pregnancy malaria. PfSPZ Vaccine without presumptive antimalarial treatment before the first vaccine dose did not show efficacy. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Sanaria.

High prevalence of asymptomatic and subpatent Plasmodium falciparum infections but no histidine-rich protein 2 gene deletion in Bouaké, Côte d'Ivoire.

This study aimed to estimate the prevalence of asymptomatic and subpatent P. falciparum infections in the city of Bouaké, Central Côte d'Ivoire, to compare the performance of three tests, and to investigate potential P. falciparum histidine-rich protein 2 (pfhrp2) gene deletions. A cross-sectional survey was conducted in nine neighborhoods in Bouaké in 2016. Matched light microscopy (LM), rapid diagnostic test (RDT), and quantitative PCR (qPCR) data were used to determine the prevalence of P. falciparum infection and compare the performance of the three diagnostic tests. Pfhrp2/3 deletions were genotyped by digital PCR. Among 2313 individuals, 97.2% were asymptomatic and 2.8% were symptomatic. P. falciparum prevalence among symptomatic individuals was 25.8%, 30.3%, and 40.9% by LM, RDT, and varATS qPCR, respectively, and among asymptomatic individuals, it was 10.3%, 12.5%, and 34.9%. Asymptomatic infections comprised 96.4% of all malaria infections, with 58.2% detectable only by varATS qPCR. Although the prevalence of asymptomatic P. falciparum infections was higher in school-age children (5-14 years: 42.0%) compared to < 5 years (17.3%) and ≥ 15 years (35.9%), subpatent infections were more likely in ≥ 15 years (70.4%) than in < 5 years (39.7%) and school-age children (41.2%). LM and RDTs were reliable only at parasite densities > 10,000 parasites/µL. Individuals who were positive according to all three tests had significantly greater parasite density (856.8 parasites/µL; 95% CI 707.3-1,038) than did those who were positive by varATS qPCR only (13.7 parasites/µL; 95% CI 11.4-16.3) (p < 0.0001). No pfhrp2 deletions were observed. The high prevalence of asymptomatic and subpatent infections highlights the need for targeted strategies to reduce malaria in urban Côte d'Ivoire.