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Background: WHO and its partners have adopted alternative control interventions since the failure to eradicate malaria worldwide in the 1960s and 1970s. The aim of these interventions has been to redesign the control interventions to make them more effective and more efficient. The purpose of this study is to assess the population impact of control interventions implemented at the community health area level., Methods: The analysis used data from the health information system on malaria cases and interventions (distribution of long-lasting insecticide-treated nets (LLINs), seasonal malaria chemoprevention (SMC), access to rapid diagnostic tests (RDT), intermittent preventive treatment for pregnant women (IPTp)) collected in the Kati health district from 2017 to 2020. And the contextual parameters (temperature, normal difference vegetation index (NDVI) and rainfall) were obtained by remote sensing. A generalized additive model was used to assess the impact of malaria control interventions on malaria cases as a function of meteorological factors., Results: The incidence of malaria varies from year to year and from health area to health area, as do meteorological factors in the study area. The distribution of long-lasting insecticide-treated nets, chemoprevention of seasonal malaria in children and access to rapid diagnostic tests for malaria were found to have a significant impact on the incidence of malaria in the population. Seasonal malaria chemoprevention was effective in reducing the incidence of malaria, while distribution of long-lasting insecticide-treated nets and access to rapid diagnostic tests increased with the number of malaria cases, reflecting efforts to distribute and use bed nets and to diagnose malaria cases among the population in the study area., Conclusion: The study showed the impact of SMC on reducing malaria cases in the population and the significant efforts in LLIN distribution and malaria case diagnosis. To further reduce the burden of malaria, sustained efforts and new interventions are needed, including improving access to rapid diagnosis and treatment in communities by developing community health workers and locally tailored mass drug administration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Katile et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The interpretation of a laboratory test result requires an appropriate reference range established in healthy subjects, and normal ranges may vary by factors such as geographic region, sex, and age. We examined hematological and clinical chemistry parameters in healthy residents at two rural vaccine trial sites: Bancoumana and Doneguebougou in Mali, West Africa. During screening of clinical studies in 2018 and 2019, peripheral blood samples from 1,192 apparently healthy individuals age 6 months to 82 years were analyzed at a laboratory accredited by the College of American Pathologists for a complete blood count, and creatinine and/or alanine aminotransferase levels. Based on manufacturers' reference range values, which are currently used in Malian clinical laboratories, abnormal values were common in this healthy population. In fact, 30.4% of adult participants had abnormal neutrophil levels and 19.8% had abnormal hemoglobin levels. Differences by sex were observed in those who were older, but not in those younger than 10 years, for several parameters, including hemoglobin, platelet, and absolute neutrophil counts in hematology, and creatinine in biochemistry. The site-specific reference intervals we report can be used in malaria vaccine clinical trials and other interventional studies, as well as in routine clinical care, to identify abnormalities in hematological and biochemical parameters among healthy Malian trial participants.

Aims: Malaria remains a health problem. The objective was to study cerebral malaria (CM) epidemiology before and after the implementation of seasonal malaria chemoprevention (SMC)., Materials and Methods: This was a retrospective cross-sectional study carried out from January 01, 2014 to December 31, 2018 in children aged 0 to 15 years hospitalized for CM at the paediatrics' department of CHU Gabriel Touré., Results: We recorded 1336 cases of CM, 803 boys and 533 girls with a sex ratio of 1.5. CM accounted for 92.1% and 83.5% respectively two years before and three years after the SMC implementation (p = 0.013). The overall lethality was 9.2% varying according to the years of follow up (p = 0.001) The SMC led to decrease of CM frequency of 8.6%., Conclusion: SMC could have an impact on the expression of severe malaria phenotypes, with an increase of frequency of CM and CM associated with pulmonary oedema, a decrease of the frequency of CM associated with severe anaemia. Prospective studies will enable to understand the increasing case lethality rate observed during SMC period., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 MalariaGEN et al.)

Introduction: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite., Areas Covered: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.', Expert Opinion: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014-2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013-15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, ( P = 0.019), whereas cerebral malaria cases decreased to 45.5% ( P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0-1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Coulibaly, Kone, Kane, Guindo, Tangara, Sissoko, Maiga, Traore, Diawara, Traore, Thera, Sissoko, Doumbo, Travassos and Thera.)

Introduction: Despite the implementation of control strategies at the national scale, the malaria burden remains high in Mali, with more than 2.8 million cases reported in 2019. In this context, a new approach is needed, which accounts for the spatio-temporal variability of malaria transmission at the local scale. This study aimed to describe the spatio-temporal variability of malaria incidence and the associated meteorological and environmental factors in the health district of Kati, Mali., Methods: Daily malaria cases were collected from the consultation records of the 35 health areas of Kati's health district, for the period 2015-2019. Data on rainfall, relative humidity, temperature, wind speed, the normalized difference vegetation index, air pressure, and land use-land cover were extracted from open-access remote sensing sources, while data on the Niger River's height and flow were obtained from the National Department of Hydraulics. To reduce the dimension and account for collinearity, strongly correlated meteorological and environmental variables were combined into synthetic indicators (SI), using a principal component analysis. A generalized additive model was built to determine the lag and the relationship between the main SIs and malaria incidence. The transmission periods were determined using a change-point analysis. High-risk clusters (hotspots) were detected using the SatScan method and were ranked according to risk level, using a classification and regression tree analysis., Results: The peak of the malaria incidence generally occurred in October. Peak incidence decreased from 60 cases per 1000 person-weeks in 2015, to 27 cases per 1000 person-weeks in 2019. The relationship between the first SI (river flow and height, relative humidity, and rainfall) and malaria incidence was positive and almost linear. A non-linear relationship was found between the second SI (air pressure and temperature) and malaria incidence. Two transmission periods were determined per year: a low transmission period from January to July-corresponding to a persisting transmission during the dry season-and a high transmission period from July to December. The spatial distribution of malaria hotspots varied according to the transmission period., Discussion: Our study confirmed the important variability of malaria incidence and found malaria transmission to be associated with several meteorological and environmental factors in the Kati district. The persistence of malaria during the dry season and the spatio-temporal variability of malaria hotspots reinforce the need for innovative and targeted strategies., Competing Interests: The authors declare no conflict of interest.

Background: While prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination., Methods: Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa)., Results: Females ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females., Conclusion: Immunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver., Competing Interests: NK, LC, PR, SC, TM, PB, BS, TR and SH are salaried employees of Sanaria Inc., the developer and owner of PfSPZ Vaccine and sponsor of the clinical trials. In addition, BS and SH have a financial interest in Sanaria Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare this study received funding from Sanaria Inc. The funder had the following involvement in the study: proposal of the study hypothesis, conduct of the ELISAs and data analysis., (Copyright © 2022 KC, Church, Riyahi, Chakravarty, Seder, Epstein, Lyke, Mordmüller, Kremsner, Sissoko, Healy, Duffy, Jongo, Nchama, Abdulla, Mpina, Sirima, Laurens, Steinhardt, Oneko, Li, Murshedkar, Billingsley, Sim, Richie and Hoffman.)

Controlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than VE against CHMI at 24 weeks in the US. To explain this finding, here we quantify differences in the genome, proteome, and predicted CD8 T cell epitopes of PfNF54 relative to 704 Pf isolates from Africa and Pf7G8. We show that Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa., (© 2022. The Author(s).)

Background: WHO recently approved a partially effective vaccine that reduces clinical malaria in children, but increased vaccine activity is required to pursue malaria elimination. A phase 1 clinical trial was done in Mali, west Africa, to assess the safety, immunogenicity, and protective efficacy of a three-dose regimen of Plasmodium falciparum sporozoite (PfSPZ) Vaccine (a metabolically active, non-replicating, whole malaria sporozoite vaccine) against homologous controlled human malaria infection (CHMI) and natural P falciparum infection., Methods: We recruited healthy non-pregnant adults aged 18-50 years in Donéguébougou, Mali, and surrounding villages (Banambani, Toubana, Torodo, Sirababougou, Zorokoro) for an open-label, dose-escalation pilot study and, thereafter, a randomised, double-blind, placebo-controlled main trial. Pilot study participants were enrolled on an as-available basis to one group of CHMI infectivity controls and three staggered vaccine groups receiving: one dose of 4·5 × 10 5 , one dose of 9 × 10 5 , or three doses of 1·8 × 10 6 PfSPZ via direct venous inoculation at approximately 8 week intervals, followed by homologous CHMI 5 weeks later with infectious PfSPZ by direct venous inoculation (PfSPZ Challenge). Main cohort participants were stratified by village and randomly assigned (1:1) to receive three doses of 1·8 × 10 6 PfSPZ or normal saline at 1, 13, and 19 week intervals using permuted block design by the study statistician. The primary outcome was safety and tolerability of at least one vaccine dose; the secondary outcome was vaccine efficacy against homologous PfSPZ CHMI (pilot study) or against naturally transmitted P falciparum infection (main study) measured by thick blood smear. Combined artesunate and amodiaquine was administered to eliminate pre-existing parasitaemia. Outcomes were analysed by modified intention to treat (mITT; including all participants who received at least one dose of investigational product; safety and vaccine efficacy) and per protocol (vaccine efficacy). This trial is registered with ClinicalTrials.gov, number NCT02627456., Findings: Between Dec 20, 2015, and April 30, 2016, we enrolled 56 participants into the pilot study (five received the 4·5 × 10 5 dose, five received 9 × 10 5 , 30 received 1·8 × 10 6 , 15 were CHMI controls, and one withdrew before vaccination) and 120 participants into the main study cohort with 60 participants assigned PfSPZ Vaccine and 60 placebo in the main study. Adverse events and laboratory abnormalities post-vaccination in all dosing groups were few, mainly mild, and did not differ significantly between vaccine groups (all p>0·05). Unexpected severe transaminitis occured in four participants: one participant in pilot phase that received 1·8 × 10 6 PfSPZ Vaccine, one participant in main phase that received 1·8 × 10 6 PfSPZ Vaccine, and two participants in the main phase placebo group. During PfSPZ CHMI, approximately 5 weeks after the third dose of 1·8 × 10 6 PfSPZ, none of 29 vaccinees and one of 15 controls became positive on thick blood smear; subsequent post-hoc PCR analysis for submicroscopic blood stage infections detected P falciparum parasites in none of the 29 vaccine recipients and eight of 15 controls during CHMI. In the main trial, 32 (58%) of 55 vaccine recipients and 42 (78%) of 54 controls became positive on thick blood smear during 24-week surveillance after vaccination. Vaccine efficacy (1-hazard ratio) was 0·51 per protocol (95% CI 0·20-0·70; log-rank p=0·0042) and 0·39 by mITT (0·04-0·62; p=0·033); vaccine efficacy (1-risk ratio) was 0·24 per-protocol (0·02-0·41; p=0·031) and 0·22 mITT (0·01-0·39; p=0·041)., Interpretation: A three-dose regimen of PfSPZ Vaccine was safe, well tolerated, and conferred 51% vaccine efficacy against intense natural P falciparum transmission, similar to 52% vaccine efficacy reported for a five-dose regimen in a previous trial., Funding: US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Sanaria., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests YA, ERJ, TM, NK, BKLS, PFB, TLR, and SLH are salaried, full-time employees of Sanaria, the developer and sponsor of Sanaria PfSPZ Vaccine. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission., Methods: In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197., Findings: Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77-0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39-0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01-0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages., Interpretation: Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention., Funding: US National Institutes of Health and Burroughs Wellcome Fund/ASTMH Fellowship., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Immunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness. Gamma delta (γδ) T cells, particularly the Vδ2+ subset, have been associated with development of clinical malaria in children. In this study, the dynamics of total γδ T cells, Vδ2+ and Vδ2- T cells were measured during a malaria transmission season in Malian adults., Methods: This study explored γδ T cell dynamics and Plasmodium falciparum infection outcomes over the course of the malaria transmission season in Malian adults enrolled in the placebo arm of a double-blind randomized vaccine trial. All volunteers were treated with anti-malarial drugs prior to the start of the transmission season and blood smears were assessed for P. falciparum infection every 2 weeks from July 2014 to January 2015. The study participants were stratified as either asymptomatic infections or clinical malaria cases. Vδ2+ and Vδ2- γδ T cell frequencies and activation (as measured by CD38 expression) were measured in all study participants at baseline and then every 2 months using a whole blood flow cytometry assay., Results: Forty of the forty-three subjects became infected with P. falciparum and, of those, 21 individuals were diagnosed with clinical malaria at least once during the season. The γδ T cell percentage and activation increased over the duration of the transmission season. Both the Vδ2+ and Vδ2- γδ T cells were activated by P. falciparum infection., Conclusion: γδ T cells increased during a malaria transmission season and this expansion was noted in both the Vδ2+ and Vδ2- γδ T cells. However, neither expansion or activation of either γδ T cell subsets discriminated study participants that had asymptomatic infections from those that had clinical malaria cases.

Introduction: Malaria is still a public health problem in Africa. Seasonal Malaria Chemoprevention (SMC) is an efficient control strategy recommended by WHO that targets children under five year old living in areas of seasonal malaria transmission. SMC uses the combination amodiaquine (AQ) - sulfadoxine-pyrimethamine (SP). However SP selects rapidly drug resistant parasites. And malaria burden may increase in older children where SMC is implemented. We initiated a pilot study to assess an alternative approach to SMC in older children in Mali., Methods: A randomized open-label clinical trial was conducted to test the efficacy and safety of SMC using artesunate - amodiaquine in school aged children in Mali. Two hundred pupils aged 6-15 years old were enrolled and randomized into two arms of 100 each, to receive either artesunate-amodiaquine (ASAQ) monthly or no intervention. Both arms were followed and clinical malaria were diagnosed and treated with arthemeter-lumefanthrine as recommended by Mali National Malaria Control Program. ASAQ was administered 3 days under study team direct observation and during 4 consecutive months starting in October 2013. Follow up was continued until April 2014., Results: Overall, 20 cases of uncomplicated clinical malaria were encountered in the Control arm and three cases in the ASAQ arm, showing a protective efficacy of 85% 95% CI [80.1-89.9] against clinical malaria. Protective efficacy against malaria infection was 69.6% 95% CI [58.6-21.4]. No effect on anemia was observed. ASAQ was well tolerated. Most common solicited adverse events were abdominal pain and headaches of mild intensity in respectively 64% and 44% of children that swallowed ASAQ., Conclusion: ASAQ is effective and well tolerated as SMC targeting older children in a peri urban setting in Mali. Its administration at schools is a feasible and accepted strategy to deliver the intervention.

Aim: Our aim was to evaluate the diagnosis and therapeutic aspects of the amoebic liver abscesses in the surgery «A» department of the University hospital Point "G"., Patients and Methods: Were included in this study, patients admitted to the surgery «A» department for amoebic liver abscess confirmed by a positive amoebic serology and the chocolate appearance of bacteria-free pus. Bacterial liver abscesses were not included into this study., Results: Over a 10-year period, 52 cases of patients diagnosed with amoebic liver abscess were collected in the department. There were 41 men and 11 women, with a sex ratio of 3.7. The mean age was 37.8 years old with extremes of 15 and 66 years. The most represented professions were farmers (36.5%) followed by salesmen (26.7%) and students (11.5%). The average outpatient visit delay time was 18.5 days with the extremes of 5 and 34 days. The most frequent clinical signs were pain in the right hypochondrium (86.5%), fever (78.8%) and hepatomegaly (61.5%). Abdominal ultrasound showed a single located abscess in 44 patients (84.6%) and these abscesses were localized in the right hepatic lobe in 34 patients(65.4%). The average volume of the abscess was 366.5 cm 3 with the extremes of 36 cm 3 and 1580 cm 3 . Amoebic serology was positive in 38 patients (80.9%). Cytobacteriological analysis of pus in 37 patients (71%) was negative. Patients underwent an ultrasound assisted needle aspiration of pus in 65.4% he. Laparotomy and a laparoscopic approach were performed in 7.7% and in 5.8%, respectively. The clinical course was uneventfulin 94.2%. The mean hospital stay duration was 16.5 days with the extremes of 4 and 29 days. No death was recorded during hospitalization., Conclusion: Amoebic liver abscess is an uncommon pathology in a surgical setting. Abdominal ultrasound andechography guided liver puncture allowed the diagnosis. Laparoscopic approach minimizes the burden of the laparotomy., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

Background: Even if rainfall and temperature are factors classically associated to malaria, little is known about other meteorological factors, their variability and combinations related to malaria, in association with river height variations. Furthermore, in suburban area, urbanization and growing population density should be assessed in relation to these environmental factors. The aim of this study was to assess the impact of combined environmental, meteorological and hydrological factors on malaria incidence through time in the context of urbanization., Methods: Population observational data were prospectively collected. Clinical malaria was defined as the presence of parasites in addition to clinical symptoms. Meteorological and hydrological factors were measured daily. For each factors variation indices were estimated. Urbanization was yearly estimated assessing satellite imaging and field investigations. Principal component analysis was used for dimension reduction and factors combination. Lags between malaria incidences and the main components were assessed by cross-correlation functions. Generalized additive model was used to assess relative impact of different environmental components, taking into account lags, and modelling non-linear relationships. Change-point analysis was used to determine transmission periods within years., Results: Malaria incidences were dominated by annual periodicity and varied through time without modification of the dynamic, with no impact of the urbanization. The main meteorological factor associated with malaria was a combination of evaporation, humidity and rainfall, with a lag of 3 months. The relationship between combined temperature factors showed a linear impact until reaching high temperatures limiting malaria incidence, with a lag 3.25 months. Height and variation of the river were related to malaria incidence (respectively 6 week lag and no lag)., Conclusions: The study emphasizes no decreasing trend of malaria incidence despite accurate access to care and control strategies in accordance to international recommendations. Furthermore, no decreasing trend was showed despite the urbanization of the area. Malaria transmission remain increase 3 months after the beginning of the dry season. Addition to evaporation versus humidity/rainfall, nonlinear relationship for temperature and river height and variations have to be taken into account when implementing malaria control programmes.

In poor African countries, where no medical and biological facilities are available, the identification of potential emerging pathogens of concern at an early stage is challenging. Head lice, Pediculus humanus capitis, have a short life, feed only on human blood and do not transmit pathogens to their progeny. They are, therefore, a perfect tool for the xenodiagnosis of current or recent human infection. This study assessed the occurrence of bacterial pathogens from head lice collected in two rural villages from Mali, where a high frequency of head lice infestation had previously been reported, using molecular methods. Results show that all 600 head lice, collected from 117 individuals, belonged to clade E, specific to West Africa. Bartonella quintana, the causative agent of trench fever, was identified in three of the 600 (0.5%) head lice studied. Our study also shows, for the first time, the presence of the DNA of two pathogenic bacteria, namely Coxiella burnetii (5.1%) and Rickettsia aeschlimannii (0.6%), detected in human head lice, as well as the DNA of potential new species from the Anaplasma and Ehrlichia genera of unknown pathogenicity. The finding of several Malian head lice infected with B. quintana, C. burnetii, R. aeschlimannii, Anaplasma and Ehrlichia is alarming and highlights the need for active survey programs to define the public health consequences of the detection of these emerging bacterial pathogens in human head lice.

Background: Plasmodium falciparum sporozite (PfSPZ) Vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against P falciparum controlled human malaria infection in malaria-naive individuals. We aimed to assess the safety and protective efficacy of PfSPZ Vaccine against naturally acquired P falciparum in malaria-experienced adults in Mali., Methods: After an open-label dose-escalation study in a pilot safety cohort, we did a double-blind, randomised, placebo-controlled trial based in Donéguébougou and surrounding villages in Mali. We recruited 18-35-year-old healthy adults who were randomly assigned (1:1) in a double-blind manner, with stratification by village and block randomisation, to receive either five doses of 2·7 × 10 5 PfSPZ or normal saline at days 0, 28, 56, 84, and 140 during the dry season (January to July inclusive). Participants and investigators were masked to group assignments, which were unmasked at the final study visit, 6 months after receipt of the last vaccination. Participants received combined artemether and lumefantrine (four tablets, each containing 20 mg artemether and 120 mg lumefantrine, given twice per day over 3 days for a total of six doses) to eliminate P falciparum before the first and last vaccinations. We collected blood smears every 2 weeks and during any illness for 24 weeks after the fifth vaccination. The primary outcome was the safety and tolerability of the vaccine, assessed as local and systemic reactogenicity and adverse events. The sample size was calculated for the exploratory efficacy endpoint of time to first P falciparum infection beginning 28 days after the fifth vaccination. The safety analysis included all participants who received at least one dose of investigational product, whereas the efficacy analyses included only participants who received all five vaccinations. This trial is registered at ClinicalTrials.gov, number NCT01988636., Findings: Between Jan 18 and Feb 24, 2014, we enrolled 93 participants into the main study cohort with 46 participants assigned PfSPZ Vaccine and 47 assigned placebo, all of whom were evaluable for safety. We detected no significant differences in local or systemic adverse events or laboratory abnormalities between the PfSPZ Vaccine and placebo groups, and only grade 1 (mild) local or systemic adverse events occurred in both groups. The most common solicited systemic adverse event in the vaccine and placebo groups was headache (three [7%] people in the vaccine group vs four [9%] in the placebo group) followed by fatigue (one [2%] person in the placebo group), fever (one [2%] person in the placebo group), and myalgia (one [2%] person in each group). The exploratory efficacy analysis included 41 participants from the vaccine group and 40 from the placebo group. Of these participants, 37 (93%) from the placebo group and 27 (66%) from the vaccine group developed P falciparum infection. The hazard ratio for vaccine efficacy was 0·517 (95% CI 0·313-0·856) by time-to-infection analysis (log-rank p=0·01), and 0·712 (0·528-0·918) by proportional analysis (p=0·006)., Interpretation: PfSPZ Vaccine was well tolerated and safe. PfSPZ Vaccine showed significant protection in African adults against P falciparum infection throughout an entire malaria season., Funding: US National Institutes of Health Intramural Research Program, Sanaria., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel(®) was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed 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., Conclusion: The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.

Although artemisinin resistance has yet to be reported in Africa, surveillance of the efficacy of artemisinin-based combination therapies (ACTs) is warranted. Here, the efficacy of artesunate + sulfadoxine-pyrimethamine (AS + SP) and artemether-lumefantrine (AL) was evaluated in Mali. Randomized open-label comparative in vivo assay of AS + SP versus AL were carried out using the 28-day follow-up World Health Organization protocol. Patients with uncomplicated falciparum malaria and at least 6 months of age were recruited between October 2010 and January 2014. A subset of these patients was selected to measure Plasmodium falciparum clearance time. Polymerase chain reaction-corrected adequate clinical and parasitological responses were 100% for AS + SP and 98.2% for AL with no significant difference (P = 0.06). The reinfection rates were comparable (P = 0.63) with 8.0% for AS + SP and 12.6% for AL. Individuals under 8 years were more susceptible to treatment failure (relative risk = 1.9; 95% confidence interval = 1.2, 3.3). Median parasite clearance half-life was 1.7 hours (interquartile range [IQR] = 1.3-2.2) for AS + SP and 1.9 hours (IQR = 1.5-2.5) for AL with no statistically significant difference (P = 0.24). Efficacy of AS + SP and AL was high. This study provides baseline information on parasite clearance half-lives after ACT treatment, particularly AS + SP, in Mali., (© The American Society of Tropical Medicine and Hygiene.)

Heterogeneity in malaria exposure is most readily recognized in areas with low-transmission patterns. By comparison, little research has been done on spatial patterns in malaria exposure in high-endemic settings. We determined the spatial clustering of clinical malaria incidence, asymptomatic parasite carriage, and Anopheles density in two villages in Mali exposed to low- and mesoendemic-malaria transmission. In the two study areas that were < 1 km(2) in size, we observed evidence for spatial clustering of Anopheles densities or malaria parasite carriage during the dry season. Anopheles density and malaria prevalence appeared associated in some of our detected hotspots. However, many households with high parasite prevalence or high Anopheles densities were located outside the identified hotspots. Our findings indicate that within small villages exposed to low- or mesoendemic-malaria transmission, spatial patterns in mosquito densities and parasite carriage are best detected in the dry season. Considering the high prevalence of parasite carriage outside detected hotspots, the suitability of the area for targeting control efforts to households or areas of more intense malaria transmission may be limited., (© The American Society of Tropical Medicine and Hygiene.)