Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.

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.

Creating culturally-informed protocols for a stunting intervention using a situated values-based approach (WeValue InSitu): a double case study in Indonesia and Senegal.

International development work involves external partners bringing expertise, resources, and management for local interventions in LMICs, but there is often a gap in understandings of relevant local shared values. There is a widespread need to better design interventions which accommodate relevant elements of local culture, as emphasised by recent discussions in global health research regarding neo-colonialism. One recent innovation is the concept of producing 'cultural protocols' to precede and guide community engagement or intervention design, but without suggestions for generating them. This study explores and demonstrates the potential of an approach taken from another field, named WeValue InSitu, to generate local culturally-informed protocols. WeValue InSitu engages stakeholder groups in meaning-making processes which 'crystallize' their envelope of local shared values, making them communicable to outsiders.Our research context is understanding and reducing child stunting, including developing interventions, carried out at the Senegal and Indonesia sites of the UKRI GCRF Action Against Stunting Hub. Each national research team involves eight health disciplines from micro-nutrition to epigenetics, and extensive collection of samples and questionnaires. Local culturally-informed protocols would be generally valuable to pre-inform engagement and intervention designs. Here we explore generating them by immediately following the group WeValue InSitu crystallization process with specialised focus group discussions exploring: what local life practices potentially have significant influence on the environments affecting child stunting, and which cultural elements do they highlight as relevant. The discussions will be framed by the shared values, and reveal linkages to them. In this study, stakeholder groups like fathers, mothers, teachers, market traders, administrators, farmers and health workers were recruited, totalling 83 participants across 20 groups. Themes found relevant for a culturally-informed protocol for locally-acceptable food interventions included: specific gender roles; social hierarchies; health service access challenges; traditional beliefs around malnutrition; and attitudes to accepting outside help. The concept of a grounded culturally-informed protocol, and the use of WeValue InSitu to generate it, has thus been demonstrated here. Future work to scope out the advantages and limitations compared to deductive culture studies, and to using other formative research methods would now be useful.

Post-malarial neurological syndrome in a Gambian adult residing in the Gambia: a case report and a review of literature.

BACKGROUND: Post malarial neurological syndrome (PMNS) occurs as a sequel of cerebral malaria which is the most deadly form of severe malaria. In holo-endemic regions (areas of high malarial transmission) all forms of severe malaria as well as cerebral malaria usually occur in children and those who are semi or non-immune like pregnant women, migrants as well as tourists. It also occurs in hypo-endemic regions (areas of limited malarial transmission with low immunity) and malaria- free zones. Survivors however may have neurologic complications after recovery. PMNS has been reported in many parts of the world. Being a sequel to cerebral malaria, it is uncommon in adults who were born and reside in a holo-endemic region all their lives. CASE REPORT: This is the case of an 18 year old Gambian who has lived in The Gambia all his life that had PMNS five days after recovery from cerebral malaria. METHODS: This was a predominantly web based literature search. The search comprise all case reports, original articles and reviews on PMNS or neurological deficits associated with malaria or noted after malaria infection. The search engines used were Google, Yahoo and Google scholar. RESULTS: A total of 62 papers were found. These were used for this review of the literature. CONCLUSION: Cerebral malaria also occurs in adults in holo-endemic areas though rare and some of the survivors may develop PMNS. It is commoner in the youth age group. There is need for further studies since the youth may be a possible new 'vulnerable group' in holoendemic areas. This may lead to the widening the targeted group for malaria control in the regions of high malarial transmission.

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

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.

Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

Introduction: More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Methods: Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. Results: In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Conclusion: Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia. Clinical Trial registration: PACTR201411000937373 (www.pactr.org).

Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal.

BACKGROUND: Expanded malaria control efforts in Sénégal have resulted in increased use of rapid diagnostic tests (RDT) to identify the primary disease-causing Plasmodium species, Plasmodium falciparum. However, the type of RDT utilized in Sénégal does not detect other malaria-causing species such as Plasmodium ovale spp., Plasmodium malariae, or Plasmodium vivax. Consequently, there is a lack of information about the frequency and types of malaria infections occurring in Sénégal. This study set out to better determine whether species other than P. falciparum were evident among patients evaluated for possible malaria infection in Kédougou, Sénégal. METHODS: Real-time polymerase chain reaction speciation assays for P. vivax, P. ovale spp., and P. malariae were developed and validated by sequencing and DNA extracted from 475 Plasmodium falciparum-specific HRP2-based RDT collected between 2013 and 2014 from a facility-based sample of symptomatic patients from two health clinics in Kédougou, a hyper-endemic region in southeastern Sénégal, were analysed. RESULTS: Plasmodium malariae (n = 3) and P. ovale wallikeri (n = 2) were observed as co-infections with P. falciparum among patients with positive RDT results (n = 187), including one patient positive for all three species. Among 288 negative RDT samples, samples positive for P. falciparum (n = 24), P. ovale curtisi (n = 3), P. ovale wallikeri (n = 1), and P. malariae (n = 3) were identified, corresponding to a non-falciparum positivity rate of 2.5%. CONCLUSIONS: These findings emphasize the limitations of the RDT used for malaria diagnosis and demonstrate that non-P. falciparum malaria infections occur in Sénégal. Current RDT used for routine clinical diagnosis do not necessarily provide an accurate reflection of malaria transmission in Kédougou, Sénégal, and more sensitive and specific methods are required for diagnosis and patient care, as well as surveillance and elimination activities. These findings have implications for other malaria endemic settings where species besides P. falciparum may be transmitted and overlooked by control or elimination activities.

[Prevalence of smoking among 741 High school students from Dakar. Carbon monoxide measurement]. / Prevalence du tabagisme parmi 741 Lycéens de Dakar : Intérêt de la mesure du monoxide de carbone.

BACKGROUND: Tobacco consumption is a net increase in our areas. In Senegal, as in other African countries, sponsorship of cultural and sporting events in schools promote tobacco use among schoolchildren. Our objective was to assess the prevalence of tobacco in the French School of Jean Mermoz of Dakar by a survey completed by a measurement of carbon monoxide (CO) in expired air. METHODS: seven hundred forty-one students (n = 402 girls and n = 339 boys), aged 11 to 18 years of French and African cultures, participated in the study. A questionnaire with several items of smoking has been distributed to them . Two weeks after the collection of questionnaires, the CO measuring for all students was conducted. RESULTS: The prevalence of smoking in High School was 23.1% and smoking was found more in boys according to the questionnaire and piCO+TM with 13.7% and 7.1% respectively. It affected over the upper age class or equal to fifteen years. The most mentioned reason for the initiation of smoking (45.4% of smokers) was curiosity with a need to be free, followed by the influence of the environment famial (44.4%) and friendly (20.5%). The measurement of carbon monoxide showed that 12.4% of our subjects had a smoking profile with 8% light smoking, 1% moderate smoking, and severe smoking was 3% of our students. A significant difference (p = 0.0021) between the two prevalences was found. CONCLUSION: The carbon monoxide intoxication by tobacco use is responsible for microcirculatory accidents such as tissue hypoxia, whereas smoking affects young students, in which the phenomenon is more precocious. Thus it is urgent to establish a policy of tobacco control in schools.

Scale-up of home-based management of malaria based on rapid diagnostic tests and artemisinin-based combination therapy in a resource-poor country: results in Senegal.

BACKGROUND: Effective case management of malaria requires prompt diagnosis and treatment within 24 hours. Home-based management of malaria (HMM) improves access to treatment for populations with limited access to health facilities. In Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP). Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861 villages in 2010. This paper reports the results of the scale-up in the targeted communities and the impact of the strategy on malaria in the formal health sector. METHODS: Data reported by the HCPs were used to assess their performance in 2009 and 2010, while routine malaria morbidity and mortality data were used to assess the impact of the HMM programme. Two high transmission regions where HMM was not implemented until 2010 were used as a comparison. RESULTS AND DISCUSSION: From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93% (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a positive RDT, 97% (4126) of whom were reported treated and cured. Home care providers referred 6871 patients to health posts for management: 6486 with a negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases. There were no deaths among these patients. In 2009 compared to 2008, incidence of suspected and confirmed malaria cases, all hospitalizations and malaria-related hospitalizations decreased in both intervention and comparison regions. Incidence of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the intervention regions, while the decrease in comparison regions was smaller and not statistically significant. CONCLUSION: Home-based management of malaria including diagnosis with RDT and treatment based on test results is a promising strategy to improve the access of remote populations to prompt and effective management of uncomplicated malaria and to decrease mortality due to malaria. When scaled-up to serve remote village communities in the regions of Senegal with the highest malaria prevalence, home care providers demonstrated excellent adherence to guidelines, potentially contributing to a decrease in hospital deaths attributed to malaria.

Frequencies and Distribution of APOE Gene Polymorphisms and Its Association With Lipid Parameters in the Senegalese Population.

Background Apolipoprotein E is a multifunctional protein that plays an important role in lipid metabolism. It is encoded by the APOE gene. However, APOE gene polymorphism has not been very well studied in the Senegalese population. Therefore, we studied allele frequencies, genotype distributions, and the relationship between APOE gene polymorphisms and lipid parameters in the Senegalese women population. Methodology This study included 110 healthy women aged 35-72 years. The mean age was 49.8 ± 8.1 years. For all subjects, lipid parameters were analyzed from fasting serum, and APOE genotypes were identified by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) based analysis. Results Variations in the frequencies and distribution of the APOE alleles and genotypes were observed (ε3: 47.3%; ε2: 43.2%; ε4: 9.6%; and ε2/ε3: 70%; ε2/ε4: 16.4%; ε3/ε3: 10.9%; ε2/ε4: 2.7%). Compared to the ε3ε3 genotype carriers, carriers of the ε3ε4 genotype had a significantly higher rate of total cholesterol (p=0.03) and no high-density lipoprotein-cholesterol (p=0.02). Univariate analysis showed that the APOE ε4 allele increases the low-density lipoprotein-cholesterol rate (OR=3.06; 95% CI: 1.16-8.22; p=0.02). Conclusion Our study has shown a difference in APOE allele frequencies and genotype distributions with a total absence of ε2ε2 and ε4ε4 genotypes in a sample of Senegalese women. We also found that APOE gene polymorphism might play a role in plasma lipid levels.

Real time and in vivo pharmaceutical and environmental studies with SpiderMass instrument.

Remote Infrared Matrix Assisted Laser Desorption Ionization (Remote IR MALDI) system (SpiderMass) with endogenous water as matrix allows to perform real-time DMPK in vivo. In this work, SpiderMass was used to analyze the impact on metabolite production or release of invalidated pro-protein PC1/3 macrophages by Short RNA (shRNA) versus scramble shRNA with Paclitaxel. Time course in vivo experiments were then performed on the inner and outer faces of patients' forearms or comedo treated with Melascreen (Ducray) containing ascorbyl glucoside. Finally, the impact of car pollution (emitted soot) on skin was also investigated. Taken together, we demonstrate that the SpiderMass instrument opens the door to clinical, pharmaceutical and environmental domains for real-time, in vivo pharmacokinetic (Drug Metabolism and PharmacoKinetics, DMPK) analysis.

[Atypical epidemic outbreak of gastroenteritis caused by rotavirus]. / Brote epidémico atípico de gastroenteritis por rotavirus.

An outbreak of Rotavirus gastroenteritis in children from 1 month to 7 years of age, detected during the summer months with the highest incidence being in August, is described here. After studying the different factors which may be related to this outbreak, it appears that the humid climatic characteristics together with the social habits of our region may have been the causes which unleashed the epidemic.

[Branhamella catarrhalis in respiratory infections]. / Branhamella catarrhalis en infecciones respiratorias.

Given the increasing interest that Branhamella catarrhalis is acquiring as a possible pathogen of the respiratory tract, we have studied 81 sputum samples of patients with respiratory problems with the aim of evaluating its clinical significance. In 22 of these patients (27.2%) the implication of B. catarrhalis could be established, either as a primary pathogen (40.9%) or in association with other pathogens, especially with Haemophilus influenzae (36.4%). Chronic bronchitis and bronchopneumonia were the clinical manifestations more frequently associated with B. catarrhalis. 79.0% of the strains were beta-lactamase producers, although only 58.0% of them were resistant to ampicillin.