Publications by authors named "Daouda Ndiaye"

121 Publications

Spatiotemporal Dynamic of the RTS,S/AS01 Malaria Vaccine Target Antigens in Senegal.

Am J Trop Med Hyg 2021 Oct 11. Epub 2021 Oct 11.

Department of Parasitology and Mycology, Cheikh Anta Diop University, Dakar, Senegal.

The RTS,S/AS01 malaria vaccine confers only moderate protection against malaria. Evidence suggests that the effectiveness of the RTS,S/AS01 vaccine depends upon the parasite population genetics, specifically regarding the circumsporozoite protein haplotypes in the population. We investigated Plasmodium falciparum circumsporozoite protein (PfCSP) gene sequences from two endemic sites in 2018 in Senegal. The PfCSP sequences were compared with those retrieved from the Pf3k genome database. In the central repeat region of PfCSP, the distribution of haplotypes differed significantly between the two study sites (Fisher's exact test, P < 0.001). No 3D7 vaccine strain haplotype was observed in this locus. In the C-terminal region, there was no significant difference in haplotypes distribution between Kedougou and Diourbel (Fischer's exact test, P = 0.122). The 3D7 haplotype frequency was 8.4% in early samples (2001-2011), but then it contracted in the subsequent years. The extensive plasticity of the P. falciparum genes coding the RTS,S/AS01 vaccine target antigens may influence the immune responses to circulating alleles. Monitoring the genetic diversity baseline and its dynamics over time and space would be instrumental in rationally improving the malaria RTS,S/AS01 vaccine and/or its implementation schedule.
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http://dx.doi.org/10.4269/ajtmh.21-0369DOI Listing
October 2021

The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response.

Viruses 2021 08 13;13(8). Epub 2021 Aug 13.

Université Cheikh Anta Diop, BP 5005, Dakar, Senegal.

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE-detected in the Yoruba population of Nigeria-conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the "emerging" nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz's critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.
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http://dx.doi.org/10.3390/v13081605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402630PMC
August 2021

The evidence for unavailability of systemic antifungals in Senegal.

Ther Adv Infect Dis 2021 Jan-Dec;8:20499361211036594. Epub 2021 Aug 9.

Service of Parasitology-Mycology, Faculty of Medicine, Pharmacy and Odontology, Cheikh Anta Diop University, Dakar, Senegal.

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http://dx.doi.org/10.1177/20499361211036594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361555PMC
August 2021

Genetic surveillance for monitoring the impact of drug use on Plasmodium falciparum populations.

Int J Parasitol Drugs Drug Resist 2021 Jul 26;17:12-22. Epub 2021 Jul 26.

Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Broad Institute, Cambridge, MA, USA; Simmons University, Boston, MA, USA. Electronic address:

The use of antimalarial drugs is an effective strategy in the fight against malaria. However, selection of drug resistant parasites is a constant threat to the continued use of this approach. Antimalarial drugs are used not only to treat infections but also as part of population-level strategies to reduce malaria transmission toward elimination. While there is strong evidence that the ongoing use of antimalarial drugs increases the risk of the emergence and spread of drug-resistant parasites, it is less clear how population-level use of drug-based interventions like seasonal malaria chemoprevention (SMC) or mass drug administration (MDA) may contribute to drug resistance or loss of drug efficacy. Critical to sustained use of drug-based strategies for reducing the burden of malaria is the surveillance of population-level signals related to transmission reduction and resistance selection. Here we focus on Plasmodium falciparum and discuss the genetic signatures of a parasite population that are correlated with changes in transmission and related to drug pressure and resistance as a result of drug use. We review the evidence for MDA and SMC contributing to malaria burden reduction and drug resistance selection and examine the use and impact of these interventions in Senegal. Throughout we consider best strategies for ongoing surveillance of both population and resistance signals in the context of different parasite population parameters. Finally, we propose a roadmap for ongoing surveillance during population-level drug-based interventions to reduce the global malaria burden.
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http://dx.doi.org/10.1016/j.ijpddr.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342550PMC
July 2021

Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium falciparum Malaria in Bohicon and Kandi, Republic of Benin, 2018-2019.

Am J Trop Med Hyg 2021 07 12;105(3):670-676. Epub 2021 Jul 12.

1Laboratory Service and Chemo Sensitivity, Benin National Malaria Control Program, Cotonou, Benin.

In 2005, artemether-lumefantrine (AL), an artemisinin-based combination therapy, was introduced as the first-line treatment of uncomplicated Plasmodium falciparum malaria in Benin. Per World Health Organization recommendations to monitor the efficacy of antimalarial treatment, we conducted a therapeutic efficacy study with AL for uncomplicated P. falciparum malaria in Bohicon and Kandi, Benin, from 2018 to 2019. Febrile patients aged 6 to 59 months with confirmed P. falciparum monoinfection received supervised doses of AL for 3 days. We monitored patients clinically and parasitologically on days 1, 2, 3, 7, 14, 21, and 28. A molecular analysis to detect mutations in the P. falciparum Kelch propeller gene (Pfk13) gene was carried out on day 0 samples. A total of 205 patients were included in the study. In Bohicon, the uncorrected adequate clinical and parasitological response (ACPR) proportion was 91.3% (95% confidence interval [CI]: 84.6-95.8%), whereas in Kandi this proportion was 96.7% (95% CI: 90.6-99.3%). Genotype-corrected ACPR proportions were 96.3% (95% CI: 90.9-99.0%) and 96.7% (95% CI: 90.6-99.3%) in Bohicon and Kandi, respectively. On day 3, 100% of patients in Bohicon and 98.9% of patients in Kandi had undetectable parasitemia. The C580Y mutation in the Pfk13 gene was not observed. AL remains effective for P. falciparum malaria in these two sites in Benin. Monitoring antimalarial efficacy and prevalence of molecular-resistance markers in Benin should be continued to allow for early detection of antimalarial resistance and to guide treatment policies.
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http://dx.doi.org/10.4269/ajtmh.21-0086DOI Listing
July 2021

Epidemiological aspects of superficial fungal infections in Koranic schools in two localities of Senegal (Thies and Touba).

Mycoses 2021 Sep 21;64(9):1132-1136. Epub 2021 Jun 21.

Cheikh Anta Diop University of Dakar, Dakar, Senegal.

Background: In developing countries, superficial fungal infections (SFI) are endemic and cause a therapeutic problem because of the duration and cost of treatment. Community living and promiscuity are key factors in the direct or indirect transmission and spread of these diseases.

Objectives: The objective was to study the epidemiological aspects of SFI, among koranic school children in two localities in Senegal.

Patients/methods: School koranic students were recruited in Thies and Touba. Diagnosis of fungal diseases was carried out using conventional techniques (microscopic examination and culture).

Results: Among 210 children, the overall prevalence of SFI was 25.71%, with 27.63% in Touba and 20.68% in Thiès. The clinical lesions were epidermophytosis (0.5%), intertrigo (0.9%), palmoplantar keratoderma (KPP) (0.9%), onychomycosis (7.7%) and tinea capitis (TC) (90%). The species responsible for the SFI were Trichophyton soudanense (85.18%), Microsporum audouinii langeronii (9.25%), Trichophyton rubrum (3.70%) and Chrysosporium keratinophilum (1.85%). The prevalence of infection was higher among boys (85.18%).

Conclusion: Superficial fungal infections are prevalent in koranic school children and attention should be given to non-dermatophytic species that could be responsible for SFI.
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http://dx.doi.org/10.1111/myc.13330DOI Listing
September 2021

Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: a guide and case study in setting up an emergency-use, laboratory-developed molecular microbiological assay.

J Clin Pathol 2021 Aug 28;74(8):496-503. Epub 2021 May 28.

Infectious Disease and Microbiome Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

Developing and deploying new diagnostic tests are difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important. During a pandemic, laboratories play a key role in helping healthcare providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, PCR remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular-based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to establishing fast and accurate diagnostic testing in crisis conditions.
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http://dx.doi.org/10.1136/jclinpath-2020-207128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311084PMC
August 2021

Comparative analysis of four malaria diagnostic tools and implications for malaria treatment in southwestern Nigeria.

Int J Infect Dis 2021 Jul 24;108:377-381. Epub 2021 May 24.

Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia.

Objectives: One of the problems encountered in malaria control and elimination is inaccurate diagnosis, resulting from the degree of sensitivity of the different malaria diagnostic tools. Even though microscopy remains the gold standard for malaria diagnosis, more sensitive and robust diagnostic tools such as polymerase chain reactions (PCR) are used in research settings to monitor interventions and track sub-microscopic infections due to some of the drawbacks of microscopy. Since diagnosis is a critical determinant for rational malaria treatment, it is imperative that accurate diagnosis must be assured for an effective treatment plan. Therefore, this study compared two routinely used point of care malaria diagnostic tools with two molecular tools and discussed their implication for malaria treatment.

Design: In this study, 436 individuals with suspected malaria were sampled and systematically tested using four methods, namely rapid diagnostic test (henceforth referred to as malaria RDT- mRDT), microscopy, nested PCR (nPCR), and quantitative PCR (qPCR). Test sensitivities and specificities were compared, and their level of concordance was determined.

Results: With nPCR as the gold standard, a false positivity rate of 42.2%, 8.9%, and 57.8% was obtained for mRDT, microscopy, and qPCR. Similarly, false negativity rates of 12.5%, 62.5%, and 0.8% were obtained for each of the methods mentioned above, respectively. Of all the tools assessed, qPCR gave the highest sensitivity (99.2%) and moderate specificity (42.2%), followed by the mRDT kit used (87.5%).

Conclusions: With the detection of a high false positivity rate based on mRDT and a substantial proportion of sub-microscopic carriers in this study area by nested/quantitative PCR, we recommend that these molecular tools should be in specialized laboratories within the region to (i) track and treat sub-microscopic carriers to prevent their contribution to malaria transmission; (ii) provide reliable epidemiological data using high throughput testing tools for evaluating malaria interventions.
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http://dx.doi.org/10.1016/j.ijid.2021.05.049DOI Listing
July 2021

infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

medRxiv 2021 May 12. Epub 2021 May 12.

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.
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http://dx.doi.org/10.1101/2021.05.10.21256855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132281PMC
May 2021

Genomic investigation of a dengue virus outbreak in Thiès, Senegal, in 2018.

Sci Rep 2021 05 14;11(1):10321. Epub 2021 May 14.

Laboratoire de Parasitologie-Mycologie, Hôpital Aristide le Dantec, Université Cheikh Anta Diop de Dakar, BP 16477, Dakar, Senegal.

Dengue virus is a major and rapidly growing public health concern in tropic and subtropic regions across the globe. In late 2018, Senegal experienced its largest dengue virus outbreak to date, covering several regions. However, little is known about the genetic diversity of dengue virus (DENV) in Senegal. Here we report complete viral genomes from 17 previously undetected DENV cases from the city of Thiès. In total we identified 19 cases of DENV in a cohort of 198 individuals with fever collected in October and November 2018. We detected 3 co-circulating serotypes; DENV 3 was the most frequent accounting for 11/17 sequences (65%), 4 (23%) were DENV2 and 2 (12%) were DENV1. Sequences were most similar to recent sequences from West Africa, suggesting ongoing local circulation of viral populations; however, detailed inference is limited by the scarcity of available genomic data. We did not find clear associations with reported clinical signs or symptoms, highlighting the importance of testing for diagnosing febrile diseases. Overall, these findings expand the known range of DENV in Senegal, and underscore the need for better genomic characterization of DENV in West Africa.
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http://dx.doi.org/10.1038/s41598-021-89070-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121849PMC
May 2021

High prevalence of asymptomatic Plasmodium infection in Bandafassi, South-East Senegal.

Malar J 2021 May 12;20(1):218. Epub 2021 May 12.

Laboratory of Parasitology and Mycology, Cheikh Anta Diop University of Dakar, Dakar, Senegal.

Background: Malaria control and elimination strategies are based on levels of transmission that are usually determined by data collected from health facilities. In endemic areas, asymptomatic Plasmodium infection is thought to represent the majority of infections, though they are not diagnosed nor treated. Therefore, there might be an underestimation of the malaria reservoir, resulting in inadequate control strategies. In addition, these untreated asymptomatic Plasmodium infections maintain transmission, making it difficult or impossible to reach malaria elimination goals. Thus, the aim of this study was to determine the prevalence of asymptomatic Plasmodium infections in southeastern Senegal.

Methods: A cross sectional study was conducted among asymptomatic individuals (N = 122) living in the village of Andiel located in Bandafassi, Kédougou, which consisted of about 200 inhabitants during the malaria transmission season in late October 2019. For each individual without malaria-related symptoms and who consented to participate, a rapid diagnostic test (RDT) was performed in the field. Results were confirmed in the laboratory with photo-induced electron transfer (PET-PCR).

Results: Malaria prevalence was 70.3% by PET-PCR and 41.8% by RDT. During the same period, the health post of the area reported 49. 1% test positivity rate by RDT. The majority of the infected study population, 92.9%, was infected with a single species and 7.1% had two or three species of Plasmodium. Plasmodium falciparum was predominant and represented 90.2% of the infections, while 6.5% were due to Plasmodium ovale and 3.3% to Plasmodium malariae. 59.4% of children targeted for SMC (zero to ten years old) were infected.

Conclusion: In southeastern Senegal, where the transmission is the highest, malaria control strategies should address asymptomatic Plasmodium infections at the community level. The results suggest that this area could be eligible for mass drug administration. Moreover, non-falciparum species could be more common and its prevalence should be determined countrywide.
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http://dx.doi.org/10.1186/s12936-021-03746-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117620PMC
May 2021

Pulmonary Madurella mycetomatis mycetoma secondary to knee eumycetoma, Senegal.

PLoS Negl Trop Dis 2021 03 25;15(3):e0009238. Epub 2021 Mar 25.

Laboratory of Parasitology and Mycology, Aristide Le Dantec University Hospital, Dakar, Senegal.

Mycetoma is a neglected tropical disease which is endemic in Senegal. Although this subcutaneous mycosis is most commonly found on the foot, extrapodal localisations have also been found, including on the leg, knee, thigh, hand, and arm. To our knowledge, no case of blood-spread eumycetoma has been reported in Senegal. Here, we report a case of pulmonary mycetoma secondary to a Madurella mycetomatis knee eumycetoma. The patient was a 41-year-old farmer living in Louga, Senegal, where the Sudano-Sahelian climate is characterised by a short and unstable rainy season and a steppe vegetation. He suffered a trauma to the right more than 20 years previously and had received treatment for more than 10 years with traditional medicine. He consulted at Le Dantec University Hospital in Dakar for treatment of a right knee mycetoma which had been diagnosed more than 10 years ago. He had experienced a chronic cough for more than a year; tuberculosis documentation was negative. Grains collected from the knee and the sputum isolated M. mycetomatis, confirmed by the rRNA gene ITS regions nucleotide sequence analysis. An amputation above the knee was performed, and antibacterial and antifungal therapy was started with amoxicillin-clavulanic acid and terbinafine. The patient died within a month of his discharge from hospital.
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http://dx.doi.org/10.1371/journal.pntd.0009238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993608PMC
March 2021

Genomic investigation of atypical malaria cases in Kanel, northern Senegal.

Malar J 2021 Feb 19;20(1):103. Epub 2021 Feb 19.

Laboratory of Parasitology and Mycology, Aristide le Dantec Hospital, Cheikh Anta Diop University, Dakar, Senegal.

Background: The diagnosis of malaria cases in regions where the malaria burden has decreased significantly and prevalence is very low is more challenging, in part because of reduced clinical presumption of malaria. The appearance of a cluster of malaria cases with atypical symptoms in Mbounguiel, a village in northern Senegal where malaria transmission is low, in September 2018 exemplifies this scenario. The collaboration between the National Malaria Control Programme (NMCP) at the Senegal Ministry of Health and the Laboratory of Parasitology and Mycology at Cheikh Anta Diop University worked together to evaluate this cluster of malaria cases using molecular and serological tools.

Methods: Malaria cases were diagnosed primarily by rapid diagnostic test (RDT), and confirmed by photo-induced electron transfer-polymerase chain reaction (PET-PCR). 24 single nucleotide polymorphisms (SNPs) barcoding was used for Plasmodium falciparum genotyping. Unbiased metagenomic sequencing and Luminex-based multi-pathogen antibody and antigen profiling were used to assess exposure to other pathogens.

Results: Nine patients, of 15 suspected cases, were evaluated, and all nine samples were found to be positive for P. falciparum only. The 24 SNPs molecular barcode showed the predominance of polygenomic infections, with identifiable strains being different from one another. All patients tested positive for the P. falciparum antigens. No other pathogenic infection was detected by either the serological panel or metagenomic sequencing.

Conclusions: This work, undertaken locally within Senegal as a collaboration between the NMCP and a research laboratory at University of Cheikh Anta Diop (UCAD) revealed that a cluster of malaria cases were caused by different strains of P. falciparum. The public health response in real time demonstrates the value of local molecular and genomics capacity in affected countries for disease control and elimination.
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http://dx.doi.org/10.1186/s12936-021-03637-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893743PMC
February 2021

Allelic diversity of MSP1 and MSP2 repeat loci correlate with levels of malaria endemicity in Senegal and Nigerian populations.

Malar J 2021 Jan 13;20(1):38. Epub 2021 Jan 13.

Laboratory of Parasitology and Mycology, Aristide Le Dantec University Hospital, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.

Background: Characterizing the genetic diversity of malaria parasite populations in different endemic settings (from low to high) could be helpful in determining the effectiveness of malaria interventions. This study compared Plasmodium falciparum parasite population diversity from two sites with low (pre-elimination) and high transmission in Senegal and Nigeria, respectively.

Methods: Parasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicated P. falciparum malaria infected patients in Senegal (94) and Nigeria (93). Allelic polymorphism at merozoite surface protein 1 (msp1) and merozoite surface protein- 2 (msp2) genes were assessed by nested PCR.

Results: The most frequent msp1 and msp2 allelic families are the K1 and IC3D7 allelotypes in both Senegal and Nigeria. Multiplicity of infection (MOI) of greater that 1 and thus complex infections was common in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 for msp1/2) than in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity of msp1 gene was higher in P. falciparum isolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles was associated with heavy than with moderate parasite density. Meanwhile, equal proportions of K1 were observed in both heavy and moderate infection types in Nigeria. The IC3D7 subtype allele of the msp2 family was the most frequent in heavily parasitaemic individuals from both countries than in the moderately infected participants.

Conclusion: The unexpectedly low genetic diversity of infections high endemic Nigerian setting compared to the low endemic settings in Senegal is suggestive of possible epidemic outbreak in Nigeria.
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http://dx.doi.org/10.1186/s12936-020-03563-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805152PMC
January 2021

Molecular epidemiology of Plasmodium falciparum by multiplexed amplicon deep sequencing in Senegal.

Malar J 2020 Nov 10;19(1):403. Epub 2020 Nov 10.

Laboratoire de Parasitologie-Mycologie, Université Cheikh Anta Diop de Dakar (UCAD), Hôpital Aristide Le Dantec, Dakar, Senegal.

Background: Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum, which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology including understanding the genetic diversity of the parasite and performing molecular surveillance of transmission has been poorly documented in Senegal. Next Generation Sequencing (NGS) offers a practical, fast and high-throughput approach to understand malaria population genetics. This study aims to unravel the population structure of P. falciparum and to estimate the allelic diversity, multiplicity of infection (MOI), and evolutionary patterns of the malaria parasite using the NGS platform.

Methods: Multiplex amplicon deep sequencing of merozoite surface protein 1 (PfMSP1) and merozoite surface protein 2 (PfMSP2) in fifty-three P. falciparum isolates from two epidemiologically different areas in the South and North of Senegal, was carried out.

Results: A total of 76 Pfmsp1 and 116 Pfmsp2 clones were identified and 135 different alleles were found, 56 and 79 belonged to the pfmsp1 and pfmsp2 genes, respectively. K1 and IC3D7 allelic families were most predominant in both sites. The local haplotype diversity (Hd) and nucleotide diversity (π) were higher in the South than in the North for both genes. For pfmsp1, a high positive Tajima's D (TD) value was observed in the South (D = 2.0453) while negative TD value was recorded in the North (D = - 1.46045) and F-Statistic (Fst) was 0.19505. For pfmsp2, non-directional selection was found with a highly positive TD test in both areas and Fst was 0.02111. The mean MOI for both genes was 3.07 and 1.76 for the South and the North, respectively, with a statistically significant difference between areas (p = 0.001).

Conclusion: This study revealed a high genetic diversity of pfmsp1 and pfmsp2 genes and low genetic differentiation in P. falciparum population in Senegal. The MOI means were significantly different between the Southern and Northern areas. Findings also showed that multiplexed amplicon deep sequencing is a useful technique to investigate genetic diversity and molecular epidemiology of P. falciparum infections.
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http://dx.doi.org/10.1186/s12936-020-03471-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654156PMC
November 2020

Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: A guide and case study in setting up an emergency-use, laboratory-developed molecular assay.

medRxiv 2020 Sep 1. Epub 2020 Sep 1.

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Developing and deploying new diagnostic tests is difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important for an effective response. In the early stages of a pandemic, laboratories play a key role in helping health care providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, polymerase chain reaction (PCR) remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility, and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to fast and accurate diagnostic testing in crisis conditions.
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http://dx.doi.org/10.1101/2020.08.26.20157297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480066PMC
September 2020

Genetic evidence for imported malaria and local transmission in Richard Toll, Senegal.

Malar J 2020 Aug 3;19(1):276. Epub 2020 Aug 3.

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Malaria elimination efforts can be undermined by imported malaria infections. Imported infections are classified based on travel history.

Methods: A genetic strategy was applied to better understand the contribution of imported infections and to test for local transmission in the very low prevalence region of Richard Toll, Senegal.

Results: Genetic relatedness analysis, based upon molecular barcode genotyping data derived from diagnostic material, provided evidence for both imported infections and ongoing local transmission in Richard Toll. Evidence for imported malaria included finding that a large proportion of Richard Toll parasites were genetically related to parasites from Thiès, Senegal, a region of moderate transmission with extensive available genotyping data. Evidence for ongoing local transmission included finding parasites of identical genotype that persisted across multiple transmission seasons as well as enrichment of highly related infections within the households of non-travellers compared to travellers.

Conclusions: These data indicate that, while a large number of infections may have been imported, there remains ongoing local malaria transmission in Richard Toll. These proof-of-concept findings underscore the value of genetic data to identify parasite relatedness and patterns of transmission to inform optimal intervention selection and placement.
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http://dx.doi.org/10.1186/s12936-020-03346-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397603PMC
August 2020

Presence of additional Plasmodium vivax malaria in Duffy negative individuals from Southwestern Nigeria.

Malar J 2020 Jun 26;19(1):229. Epub 2020 Jun 26.

Genomic Epidemiology Laboratory, Division of Vector Borne Diseases, ICMR-National Institute of Research in Tribal Health, Jabalpur, India.

Background: Malaria in sub-Saharan Africa (sSA) is thought to be mostly caused by Plasmodium falciparum. Recently, growing reports of cases due to Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax have been increasingly observed to play a role in malaria epidemiology in sSA. This in fact is due to the usage of very sensitive diagnostic tools (e.g. PCR), which have highlighted the underestimation of non-falciparum malaria in this sub-region. Plasmodium vivax was historically thought to be absent in sSA due to the high prevalence of the Duffy negativity in individuals residing in this sub-continent. Recent studies reporting detection of vivax malaria in Duffy-negative individuals from Mali, Mauritania, Cameroon challenge this notion.

Methods: Following previous report of P. vivax in Duffy-negative individuals in Nigeria, samples were further collected and assessed RDT and/or microscopy. Thereafter, malaria positive samples were subjected to conventional PCR method and DNA sequencing to confirm both single/mixed infections as well as the Duffy status of the individuals.

Results: Amplification of Plasmodium gDNA was successful in 59.9% (145/242) of the evaluated isolates and as expected P. falciparum was the most predominant (91.7%) species identified. Interestingly, four P. vivax isolates were identified either as single (3) or mixed (one P. falciparum/P. vivax) infection. Sequencing results confirmed all vivax isolates as truly vivax malaria and the patient were of Duffy-negative genotype.

Conclusion: Identification of additional vivax isolates among Duffy-negative individuals from Nigeria, substantiate the expanding body of evidence on the ability of P. vivax to infect RBCs that do not express the DARC gene. Hence, such genetic-epidemiological study should be conducted at the country level in order to evaluate the true burden of P. vivax in Nigeria.
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http://dx.doi.org/10.1186/s12936-020-03301-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318376PMC
June 2020

Efficacy and safety of artemisinin-based combination therapy and the implications of Pfkelch13 and Pfcoronin molecular markers in treatment failure in Senegal.

Sci Rep 2020 06 1;10(1):8907. Epub 2020 Jun 1.

Department of Parasitology and Mycology, Cheikh Anta Diop University, Avenue Cheikh Anta Diop, BP 5005 Fann, Dakar, Senegal.

In 2006, Senegal adopted artemisinin-based combination therapy (ACT) as first-line treatment in the management of uncomplicated malaria. This study aimed to update the status of antimalarial efficacy more than ten years after their first introduction. This was a randomized, three-arm, open-label study to evaluate the efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DP) in Senegal. Malaria suspected patients were screened, enrolled, treated, and followed for 28 days for AL and ASAQ arms or 42 days for DP arm. Clinical and parasitological responses were assessed following antimalarial treatment. Genotyping (msp1, msp2 and 24 SNP-based barcode) were done to differentiate recrudescence from re-infection; in case of PCR-confirmed treatment failure, Pfk13 propeller and Pfcoronin genes were sequenced. Data was entered and analyzed using the WHO Excel-based application. A total of 496 patients were enrolled. In Diourbel, PCR non-corrected/corrected adequate clinical and parasitological responses (ACPR) was 100.0% in both the AL and ASAQ arms. In Kedougou, PCR corrected ACPR values were 98.8%, 100% and 97.6% in AL, ASAQ and DP arms respectively. No Pfk13 or Pfcoronin mutations associated with artemisinin resistance were found. This study showed that AL, ASAQ and DP remain efficacious and well-tolerated in the treatment of uncomplicated P. falciparum malaria in Senegal.
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http://dx.doi.org/10.1038/s41598-020-65553-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264303PMC
June 2020

A twenty-eight-year laboratory-based retrospective trend analysis of malaria in Dakar, Senegal.

PLoS One 2020 15;15(5):e0231587. Epub 2020 May 15.

Department of Parasitology, Cheikh Anta Diop University, Dakar, Senegal.

Introduction: Health facility-based records offer a rich source of information to understand trends and changes in malaria cases over time. This study is aimed at determining the changes in malaria occurrence over the last 28 years, from 1989 to 2016 in Dakar, Senegal.

Methods: Laboratory suspected and confirmed malaria records from 1989 to 2016 were reviewed from the laboratory registers of the Laboratory of Parasitology and Mycology of Aristide Le Dantec Hospital. Interrupted time series (ITS) analysis was used to estimate the changes by comparing malaria cases post-intervention (2006-2016) with that of the pre-intervention (1989-2005) period.

Results: A total of 5,876 laboratory confirmed malaria cases were reported out of 29,852 tested cases, with total slide positivity rate (SPR) of 19.7%. Malaria case counts exhibited a fluctuating trend with major peaks occurring in the years 1995 and 2003 with SPR of 42.3% and 42.5%, respectively. Overall, a remarkable decline in the total number of laboratory confirmed malaria cases was observed over the last 28 years. P. falciparum was almost the only reported species, accounting for 99.98% of cases. The highest SPR was observed in the age group of under five years during the pre-intervention period while this shifted to the age group of 6-15 years old for the subsequent years. Two major malaria peak seasons were observed: one in September during the pre-intervention period and the other in November for the post-intervention period. The ITS analysis showed a dramatic decline of 83.6% in SPR following the scale-up of interventions in 2006.

Conclusion: A remarkable decline in laboratory confirmed malaria cases in Dakar over 28 years was observed. The period of rapid decline in malaria SPR coincided with the scale-up in interventions beginning in 2006 with the introduction of ACTs, followed by the widespread introduction in 2008 of bed nets treated with insecticides. Robust surveillance data should be maintained in the context of malaria elimination efforts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231587PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228107PMC
July 2020

Unprecedented Kinetic Inertness for a Mn -Bispidine Chelate: A Novel Structural Entry for Mn -Based Imaging Agents.

Angew Chem Int Ed Engl 2020 07 18;59(29):11958-11963. Epub 2020 May 18.

Centre de Biophyisique Moléculaire, CNRS UPR 4301, Université d'Orléans, rue Charles Sadron, 45071, Orléans, France.

The search for more biocompatible alternatives to Gd -based MRI agents, and the interest in Mn for PET imaging call for ligands that form inert Mn chelates. Given the labile nature of Mn , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L endows its Mn complex with exceptional kinetic inertness. Indeed, MnL did not show any dissociation for 140 days in the presence of 50 equiv. of Zn (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A-EA have dissociation half-lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL (4.28 mm  s at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL . Additionally, L could be radiolabeled with Mn and the complex revealed good stability in biological media.
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http://dx.doi.org/10.1002/anie.202003685DOI Listing
July 2020

Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal.

Malar J 2020 Mar 30;19(1):134. Epub 2020 Mar 30.

Laboratory of Parasitology and Mycology, Aristide le Dantec Hospital, Cheikh Anta Diop University, Dakar, Senegal.

Background: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency.

Methods: Here, an amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal.

Results: In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region.

Conclusion: As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.
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http://dx.doi.org/10.1186/s12936-020-03193-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106636PMC
March 2020

Genetic polymorphism of Merozoite Surface Protein 1 (msp1) and 2 (msp2) genes and multiplicity of infection across various endemic areas in Senegal.

Afr Health Sci 2019 Sep;19(3):2446-2456

Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, PO Box 5005, Dakar, Senegal.

Introduction: Despite a significant decline in Senegal, malaria remains a burden in various parts of the country. Assessment of multiplicity of infection and genetic diversity of parasites population could help in monitoring of malaria control.

Objective: To assess genetic diversity and multiplicity of infection in isolates from three areas in Senegal with different malaria transmissions.

Methods: 136 blood samples were collected from patients with uncomplicated malaria in Pikine, Kedougou and Thies. Polymorphic loci of msp1 and 2 (Merozoite surface protein-1 and 2) genes were amplified by nested PCR.

Results: For msp1gene, K1 allelic family was predominant with frequency of 71%. Concerning msp2 gene, IC3D7 allelic family was the most represented with frequency of 83%. Multiclonal isolates found were 36% and 31% for msp1et msp2 genes respectively. The MOI found in all areas was 2.56 and was statistically different between areas (P=0.024). Low to intermediate genetic diversity were found with heterozygosity range (He=0,394-0,637) and low genetic differentiation (Fst msp1= 0.011; Fst msp2=0.017) were observed between population within the country.

Conclusion: Low to moderate genetic diversity of strains and MOI disparities were found in Senegal.
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http://dx.doi.org/10.4314/ahs.v19i3.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040301PMC
September 2019

Cyclopentadienone Iron Tricarbonyl Complexes-Catalyzed Hydrogen Transfer in Water.

Molecules 2020 Jan 20;25(2). Epub 2020 Jan 20.

Normandie Univ., LCMT, ENSICAEN, UNICAEN, CNRS, 6 boulevard du Maréchal Juin, 14050 Caen, France.

The development of efficient and low-cost catalytic systems is important for the replacement of robust noble metal complexes. The synthesis and application of a stable, phosphine-free, water-soluble cyclopentadienone iron tricarbonyl complex in the reduction of polarized double bonds in pure water is reported. In the presence of cationic bifunctional iron complexes, a variety of alcohols and amines were prepared in good yields under mild reaction conditions.
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http://dx.doi.org/10.3390/molecules25020421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024363PMC
January 2020

Clustering of asymptomatic Plasmodium falciparum infection and the effectiveness of targeted malaria control measures.

Malar J 2020 Jan 21;19(1):33. Epub 2020 Jan 21.

School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, New Orleans, LA, 70112, USA.

Background: Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal.

Methods: Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys.

Results: These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014-2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural-urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa.

Conclusions: From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.
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http://dx.doi.org/10.1186/s12936-019-3063-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975028PMC
January 2020

A Comparative Study on Phenotypic versus ITS-Based Molecular Identification of Dermatophytes Isolated in Dakar, Senegal.

Int J Microbiol 2019 18;2019:6754058. Epub 2019 Dec 18.

Laboratoire de Parasitologie-Mycologie, CHU Aristide Le Dantec, BP 5005, Dakar, Senegal.

Classically, dermatophytes are identified by phenotypic methods even if these methods, sometimes, remain difficult or uncertain. On the other hand, nucleotide sequence analysis of internal transcribed spacers (ITS) of rDNA has proved to be a useful method for identification of dermatophytes. The objective of this study was to compare the phenotypic method with DNA sequencing of the ITS regions for identification of dermatophyte species isolated in Dakar, Senegal. A collection of thirty-two strains of dermatophytes were isolated from patients suffering from dermatophytosis. Mycological identification revealed ( = 13), ( = 10), ( = 5), and one strain for each of the following species: , , and and one unidentified strain. For comparison, ITS-based PCR and DNA sequencing were applied for identification of the isolated dermatophytes. ITS sequences showed, in BLAST search analysis, 99-100% of similarity. Identification of dermatophyte isolates by conventional methods was confirmed by DNA sequencing of the ITS regions in 84% of cases. Discrepancies concern mostly misidentified as . PCR sequencing provided an excellent tool for identifying dermatophyte strains that do not present typical morphological characteristics. It was also able to give correct identification of an atypical strain of responsible of mycetoma of the scalp.
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http://dx.doi.org/10.1155/2019/6754058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942864PMC
December 2019

Analysis of anti-Plasmodium IgG profiles among Fulani nomadic pastoralists in northern Senegal to assess malaria exposure.

Malar J 2020 Jan 13;19(1):15. Epub 2020 Jan 13.

Department of Parasitology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal.

Background: Northern Senegal is a zone of very low malaria transmission, with an annual incidence of < 5/1000 inhabitants. This area, where the Senegal National Malaria Control Programme has initiated elimination activities, hosts Fulani, nomadic, pastoralists that spend the dry season in the south where malaria incidence is higher (150-450/1000 inhabitants) and return to the north with the first rains. Previous research demonstrated parasite prevalence of < 1% in this Fulani population upon return from the south, similar to that documented in the north in cross-sectional surveys.

Methods: A modified snowball sampling survey of nomadic pastoralists was conducted in five districts in northern Senegal during September and October 2014. Demographic information and dried blood spots were collected. Multiplex bead-based assays were used to assess antibody responses to merozoite surface protein (MSP-1) antigen of the four primary Plasmodium species, as well as circumsporozoite protein (CSP) and liver stage antigen (LSA-1) of Plasmodium falciparum.

Results: In the five study districts, 1472 individuals were enrolled, with a median age of 22 years (range 1 to 80 years). Thirty-two percent of subjects were under 14 years and 57% were male. The overall seroprevalence of P. falciparum MSP-1, CSP and LSA-1 antibodies were 45, 12 and 5%, respectively. Plasmodium falciparum MSP-1 antibody responses increased significantly with age in all study areas, and were significantly higher among males. The highest seroprevalence to P. falciparum antigens was observed in the Kanel district (63%) and the lowest observed in Podor (28%). Low seroprevalence was observed for non-falciparum species in all the study sites: 0.4, 0.7 and 1.8%, respectively, for Plasmodium ovale, Plasmodium vivax and Plasmodium malariae MSP-1. Antibody responses to P. vivax were observed in all study sites except Kanel.

Conclusion: Prevalence of P. falciparum MSP-1 antibodies and increases by study participant age provided data for low levels of exposure among this transient nomadic population. In addition, antibody responses to P. falciparum short half-life markers (CSP and LSA-1) and non-falciparum species were low. Further investigations are needed to understand the exposure of the Fulani population to P. vivax.
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http://dx.doi.org/10.1186/s12936-020-3114-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958760PMC
January 2020

Geographical distribution of mycetoma cases in senegal over a period of 18 years.

Mycoses 2020 Mar 14;63(3):250-256. Epub 2020 Jan 14.

Cheikh Anta Diop University of Dakar, Dakar, Senegal.

Background: Mycetoma is a pathological process in which fungal or actinomycotic agents of exogenous origin produce grains. In the absence of data on the global burden, it is important to map mycetoma cases, which are useful to implement control strategies.

Objective: The objective of this study was to map mycetoma cases diagnosed in Senegal over a period of eighteen years.

Methodology: The cases of mycetoma identified in the laboratory of Mycology at Aristide Le Dantec Hospital were extracted from the notebooks; information on the dates of collection, geographical origin and fungal agent identified was entered in Excel and analysed.

Results: Three hundred and thirty-seven cases of mycetoma were diagnosed from 1993 to 2016 at Aristide Le Dantec Hospital. Mapping shows that overall, the western zone presented the majority of cases 47% (120), followed, respectively, by the central zone 32% (80), the northern zone 18% (47) and the southern zone 2% (6). However, over the years, this distribution is different with a decrease in cases from the periods 1993-2000 and 2011-2016 of 19% in the western and a progressive increase of cases in northern and central zones of, respectively, 13% and 14%. In the 1990s, the cases were predominant in Dakar, Louga and Diourbel. During 2011-2016, Thies, Diourbel, Fouta and Louga presented more cases.

Conclusion: The spatial distribution of mycetoma in Senegal changed over the years, most frequent in the west of the country, and during 1993 to 2000, mycetoma is now more common in the north.
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http://dx.doi.org/10.1111/myc.13037DOI Listing
March 2020

Serological Data Shows Low Levels of Chikungunya Exposure in Senegalese Nomadic Pastoralists.

Pathogens 2019 Jul 27;8(3). Epub 2019 Jul 27.

Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

The chikungunya virus (CHIKV) is spread by and mosquitos worldwide; infection can lead to disease including joint pain, fever, and rash, with some convalescent persons experiencing chronic symptoms. Historically, CHIKV transmission has occurred in Africa and Asia, but recent outbreaks have taken place in Europe, Indonesia, and the Americas. From September to October 2014, a survey was undertaken with nomadic pastoralists residing in the northeast departments of Senegal. Blood dried on filter paper (dried blood spots; DBS) were collected from 1465 participants of all ages, and assayed for Immunoglobulin G (IgG) antibodies against CHIKV E1 antigen by a bead-based multiplex assay. The overall seroprevalence of all participants to CHIKV E1 was 2.7%, with no persons under 10 years of age found to be antibody positive. Above 10 years of age, clear increases of seroprevalence and IgG levels were observed with increasing age; 7.6% of participants older than 50 years were found to be positive for anti-CHIKV IgG. Reported net ownership, net usage, and gender were all non-significant explanatory variables of seropositivity. These data show a low-level historical exposure of this pastoralist population to CHIKV, with no evidence of recent CHIKV transmission in the past decade.
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http://dx.doi.org/10.3390/pathogens8030113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789836PMC
July 2019

Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia.

Malar J 2019 Jul 16;18(1):239. Epub 2019 Jul 16.

Institute for Health Research, Epidemiological Surveillance and Training (IRESSEF), Dakar, Senegal.

Background: The Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) is an important P. falciparum merozoite ligand that mediates invasion of erythrocytes by interacting with a chymotrypsin-sensitive "receptor Z". A large deletion polymorphism is found in the c-terminal ectodomain of this protein in many countries around the world, resulting in a truncated, but expressed protein. The varying frequencies by region suggest that there could be region specific immune selection at this locus. Therefore, this study was designed to determine temporal changes in the PfRh2b deletion polymorphism in infected individuals from Thiès (Senegal) and Western Gambia (The Gambia). It was also sought to determine the selective pressures acting at this locus and whether prevalence of the deletion in isolates genotyped by a 24-SNP molecular barcode is linked to background genotype or whether there might be independent selection acting at this locus.

Methods: Infected blood samples were sourced from archives of previous studies conducted between 2007 and 2013 at SLAP clinic in Thiès and from 1984 to 2013 in Western Gambia by MRC Unit at LSHTM, The Gambia. A total of 1380 samples were screened for the dimorphic alleles of the PfRh2b using semi-nested Polymerase Chain Reaction PCR. Samples from Thiès were previously barcoded.

Results: In Thiès, a consistent trend of decreasing prevalence of the PfRh2b deletion over time was observed: from 66.54% in 2007 and to 38.1% in 2013. In contrast, in Western Gambia, the frequency of the deletion fluctuated over time; it increased between 1984 and 2005 from (58.04%) to (69.33%) and decreased to 47.47% in 2007. Between 2007 and 2012, the prevalence of this deletion increased significantly from 47.47 to 83.02% and finally declined significantly to 57.94% in 2013. Association between the presence of this deletion and age was found in Thiès, however, not in Western Gambia. For the majority of isolates, the PfRh2b alleles could be tracked with specific 24-SNP barcoded genotype, indicating a lack of independent selection at this locus.

Conclusion: PfRh2b deletion was found in the two countries with varying prevalence during the study period. However, these temporal and spatial variations could be an obstacle to the implementation of this protein as a potential vaccine candidate.
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http://dx.doi.org/10.1186/s12936-019-2868-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636118PMC
July 2019
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