ABSTRACT
BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.
Subject(s)
Antimalarials , Drug Resistance , Mutation , Plasmodium falciparum , Senegal , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Drug Resistance/genetics , Antimalarials/pharmacology , Antimalarials/therapeutic use , Retrospective Studies , Humans , Malaria, Falciparum/parasitology , Malaria, Falciparum/epidemiology , Polymorphism, Single Nucleotide , Protozoan Proteins/genetics , Haplotypes , Membrane Transport Proteins/geneticsABSTRACT
BACKGROUND: Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal. METHODS: This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists' ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software. RESULTS: A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values. CONCLUSION: This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.
Subject(s)
Malaria , Humans , Senegal , Reproducibility of Results , Malaria/diagnosis , Malaria/parasitology , Laboratories , Hospitals, UniversityABSTRACT
Inherited epidermolysis bullosa is a rare condition that often present at birth with skin blisters and erosions. They are associated with defective cohesion of the dermis and epidermis. There are 3 principal types: Simple, junctional and dystrophic. The severity of the condition is quite variable. The most severe forms are incompatible with life. The most common types in our country are the severe ones such as the Hallopeau -Siemens subtype. Hands and mucosal areas can develop synechia. We report here a case of dystrophic epidermolysis bullosa in a 27-year-old woman whose finger lesion was managed surgically. This treatment consisted of complete removal of constrictions and adhesions, accompanied by use of a Hueston flap and skin graft to repair the tissue deficit. The patient's clinical course required several repeat operations. This surgery allowed the possible total loss of hand function to be delayed but the inevitable progression of the illness made the treatment somewhat disappointing. Psychosocial implications are very significant in our setting.