Oumar Gaye

Introduction: A combination of mefloquine associated with artesunate (AS-MQ) was the first artemisinin-based combination therapy (ACT) to be used widely for acute uncomplicated P. falciparum malaria. Methods: Individual patient data from 31 studies of patients with uncomplicated falciparum malaria treated with various AS-MQ regimens (target mefloquine dose 25 mg/kg), conducted in Asia, Africa and South America, were pooled and analysed to investigate the effects of MQ mg/kg dosing on malaria recurrence and other clinical, parasitological and tolerability endpoints. Results: A total of 6,761 patients were enrolled in clinical studies conducted between 1995 and 2018; the majority (74%) were from Asia. The median age of study participants was 18 years (interquartile range IQR 8–30 years), of whom 13.5% (915/6761) were aged less than 5 years old. Participants received an estimated median [range] total mg/kg dose of mefloquine and artesunate of 25 [6.8–60] and 12 [3.6–33.3] respectively, and 1,572 (23.4%) participants were treated with the coformulation. The PCR-corrected recrudescence rate 42 days after any ASMQ treatment was 2.4% for patients enrolled in Asia and 2.5% in Africa, before artemisinin resistance emerged. Corresponding rates in children aged 1 to < 5 years were 2.9% and 3.3%. After adjusting for background artemisinin resistance, the hazard of recrudescence was higher in children aged 1 to < 5 years than in adults in Asia, but not in Africa (Asia, HR 3.01, 95%CI 1.60–5.64, p < 0.001; Africa HR 5.18, 95% CI 0.61–44.28, p = 0.133). There was only one recrudescent infection in South America. A significant MQ dose–effect was observed in Asia in patients treated with 3-dose regimens (AHR 0.89, 95% CI 0.83–0.96, p = 0.003 for 1 mg/kg increase in dose). Vomiting rates within an hour of dosing were highest in children 1- 5 years of age (n = 140) at 3.4% doses (13/378) compared to 1.7% (20/1,168) in children 5–11 years (n = 476), and 1.1% (47/4,191) in patients 12 years of age or older (n = 2027) (p < 0.001, test for trend). Conclusion: AS-MQ administered over three days is a highly efficacious ACT in low to moderate transmission areas without artemisinin resistance. While further optimisation of the mefloquine dose in the coformulation in children aged 1–5 years could be considered, dose-related early vomiting is highest in this age group and may preclude this.

Visceral leishmaniasis (VL) is an infectious disease caused by protozoa of the genus Leishmania. Sporadic cases are observed in nonendemic areas and often associated with limited foci; therefore, the disease is easily overlooked. In addition, other diseases have similar clinical symptoms, which make it difficult for clinicians to make an accurate diagnosis and to provide effective treatment. We identified visceral leishmaniasis in a 4-year-old child in Pikine, Senegal. The patient was admitted to the Pikine National Teaching Hospital for haemorrhagic, tumoral, and infectious syndromes. At admission, the patient presented with epistaxis and gingivorrhagia, a severe anaemic syndrome poorly tolerated, a systemic inflammatory response syndrome with fever at 39.5C, a tumoral syndrome with 11cm of hepatomegaly and 12cm of type IV splenomegaly, and noninflammatory macropoly adenopathies. A spinal cord puncture was performed, and direct microscopy examination of the sample after GIEMSA staining revealed amastigote forms of Leishmania. The PCR amplification of extracted DNA from the bone marrow aspiration using specific primers for VL (forward and reverse) confirmed that VL was responsible for the infection. A treatment with meglumine antimoniate (Glucantime) was given and it gave a successful outcome with remission of clinical symptoms and favourable evolution with 3months hindsight. Conclusion. This visceral leishmaniasis case diagnosis in Senegal has shown that, apart from haematological malignancies, this disease must be considered in combination with a tumor syndrome, haemorrhagic syndrome, and infectious syndrome.

Background: The ESSENCE on Health Research initiative established a Working Group on Review of Investments in 2018 to improve coordination and collaboration among funders of health research capacity strengthening. The Working Group comprises more than a dozen ESSENCE members, including diverse representation by geography, country income level, the public sector, and philanthropy. Objective: The overall goal of the Working Group is increased research on national health priorities as well as improved pandemic preparedness, and, ultimately, fewer countries with very limited research capacity. Methods: We developed a basic set of metrics for national health research capacity, assessed different models of coordination and collaboration, took a deeper dive into eight countries to characterize their national research capacity, and began to identify opportunities to better coordinate our investments. In this article, we summarize the presentations, discussions, and outcomes of our second annual (virtual) meeting, which had more than 100 participants representing funders, researchers, and other stakeholders from higher- and lower-income countries worldwide. Findings and conclusions: Presentations on the first day included the keynote speaker, Dr. Soumya Swaminathan, chief scientist of the World Health Organization (WHO), and updates on data and metrics for research capacity, which are critical to establish targets, road maps, and budgets. The second day focused on improving collaboration and coordination among funders and other stakeholders, the potential return on investment for health research, ongoing work to increase coordination at the country level, and examples of research capacity strengthening efforts in diverse health research areas from around the world. We concluded that an intentional data- and metric-driven approach to health research capacity strengthening, emphasizing coordination among funders, local leadership, and equitable partnerships and allocation of resources, will enhance the health systems of resource-poor countries as well as the world’s pandemic preparedness.

Widespread of insecticide resistance amongst the species of the Anopheles gambiae complex continues to threaten vector control in Senegal. In this study, we investigated the presence and evolution of the Ace-1 and Gste2 resistance genes in natural populations of Anopheles gambiae s.l., the main malaria vector in Senegal. Using historical samples collected from ten sentinel health districts, this study focused on three different years (2013, 2017, and 2018) marking the periods of shift between the main public health insecticides families (pyrethroids, carbamates, organophosphates) used in IRS to track back the evolutionary history of the resistance mutations on the Ace-1 and Gste2 loci. The results revealed the presence of four members of the Anopheles gambiae complex, with the predominance of An. arabiensis followed by An. gambiae, An. coluzzii, and An. gambiae–coluzzii hybrids. The Ace-1 mutation was only detected in An. gambiae and An. gambiae–coluzzii hybrids at low frequencies varying between 0.006 and 0.02, while the Gste2 mutation was found in all the species with a frequency ranging between 0.02 and 0.25. The Ace-1 and Gste2 genes were highly diversified with twenty-two and thirty-one different haplotypes, respectively. The neutrality tests on each gene indicated a negative Tajima’s D, suggesting the abundance of rare alleles. The presence and spread of the Ace-1 and Gste2 resistance mutations represent a serious threat to of the effectiveness and the sustainability of IRS-based interventions using carbamates or organophosphates to manage the widespread pyrethroids resistance in Senegal. These data are of the highest importance to support the NMCP for evidence-based vector control interventions selection and targeting.

"Cooperation in Countering Artemisinin Resistance in Africa: Learning from COVID-19" published on 12 Apr 2022 by The American Society of Tropical Medicine and Hygiene.

The evolution and spread of insecticide resistance mechanisms amongst malaria vectors across the sub-Saharan Africa threaten the effectiveness and sustainability of current insecticide-based vector control interventions. However, a successful insecticide resistance management plan relies strongly on evidence of historical and contemporary mechanisms circulating. This study aims to retrospectively determine the evolution and spread of pyrethroid resistance mechanisms among natural Anopheles gambiae s.l. populations in Senegal. Samples were randomly drawn from an existing mosquito sample, collected in 2013, 2017, and 2018 from 10 sentinel sites monitored by the Senegalese National Malaria Control Programme (NMCP). Molecular species of An. gambiae s.l. and the resistance mutations at the Voltage-gated Sodium Channel 1014 (Vgsc-1014) locus were characterised using PCR-based assays. The genetic diversity of the Vgsc gene was further analyzed by sequencing. The overall species composition revealed the predominance of Anopheles arabiensis (73.08%) followed by An. gambiae s.s. (14.48%), Anopheles coluzzii (10.94%) and Anopheles gambiae–coluzii hybrids (1.48%). Both Vgsc-1014F and Vgsc-1014S mutations were found in all studied populations with a spatial variation of allele frequencies from 3% to 90%; and 7% to 41%, respectively. The two mutations have been detected since 2013 across all the selected health districts, with Vgsc-L1014S frequency increasing over the years while Vgsc-1014F decreasing. At species level, the Vgsc-1014F and Vgsc-1014S alleles were more frequent amongst An. gambiae s.s. (70%) and An. arabiensis (20%). The Vgsc gene was found to be highly diversified with eight different haplotypes shared between Vgsc-1014F and Vgsc-1014S. The observed co-occurrence of Vgsc-1014F and Vgsc-1014S mutations suggest that pyrethroid resistance is becoming a widespread phenomenon amongst malaria vector populations, and the NMCP needs to address this issue to sustain the gain made in controlling malaria.

The emergence and spread of insecticide resistance among the main malaria vectors is threatening the effectiveness of vector control interventions in Senegal. The main drivers of this resistance in the Anopheles gambiae complex (e.g., An. gambiae and Anopheles coluzzii) remains poorly characterized in Senegal. Here we characterized the main target site and metabolic resistances mechanisms among the An. gambiae and An. coluzzii populations from their sympatric and allopatric or predominance area in Senegal. Larvae and pupae of An. gambiae s.l. were collected, reared to adulthood, and then used for insecticides susceptibility and synergist assays using the WHO (World Health Organisation) test kits for adult mosquitoes. The TaqMan method was used for the molecular characterization of the main target site insecticide resistance mechanisms (Vgsc-1014F, Vgsc-1014S, N1575Y and G119S). A RT-qPCR (Reverse Transcriptase-quantitative Polymerase Chaine Reaction) was performed to estimate the level of genes expression belonging to the CYP450 (Cytochrome P450) family. Plasmodium infection rate was investigated using TaqMan method. High levels of resistance to pyrethroids and DDT and full susceptibility to organophosphates and carbamates where observed in all three sites, excepted a probable resistance to bendiocarb in Kedougou. The L1014F, L1014S, and N1575Y mutations were found in both species. Pre-exposure to the PBO (Piperonyl butoxide) synergist induced a partial recovery of susceptibility to permethrin and full recovery to deltamethrin. Subsequent analysis of the level of genes expression, revealed that the CYP6Z1 and CYP6Z2 genes were over-expressed in wild-resistant mosquitoes compared to the reference susceptible strain (Kisumu), suggesting that both the metabolic resistance and target site mutation involving kdr mutations are likely implicated in this pyrethroid resistance. The presence of both target-site and metabolic resistance mechanisms in highly pyrethroid-resistant populations of An. gambiae s.l. from Senegal threatens the effectiveness and the sustainability of the pyrethroid-based tools and interventions currently deployed in the country. The Kdr-west mutation is widely widespread in An. coluzzii sympatric population. PBO or Duo nets and IRS (Indoor Residual Spraying) with organophosphates could be used as an alternative measure to sustain malaria control in the study area.

Several efforts are being made now for malaria elimination with a goal for eradication. New tools and strategies are being developed and there is currently renewed political engagement and interest. Several technical groups have produced a guide on elimination for policymakers and indicated different research questions to be addressed. The World Health Assembly resolution and the United Nations General Assembly convened a high-level roundtable “From High Burden to High Impact: Getting back on track to end Malaria”. In Africa, the Head of states pronounced a vision for an Africa free of malaria and launched the slogan “Zero malaria starts with me”. Massive efforts to sustain research capacity in the endemic countries will be critical. It will be important to both increase domestic financing, and advocate to sustain and increase funding from major donor countries. It is unethical to continue to observe deaths of so many children in malaria endemic countries, the most vulnerable populations. Considering malaria eradication as a vision and working with all the opportunities we now have could accelerate the process. Eliminating malaria with a country regional approach and progressing step by step will give us consistent information on our way towards eradication.

Acute Respiratory Infections (ARI) are common causes of febrile illnesses in many settings in Senegal. These infections are usually managed presumptively due to lack of appropriate diagnostic tools. This situation, can lead to poor management of febrile illness or antibiotic misuse. In addition, there are limited data on the spectrum of pathogens commonly responsible for these ARI. This study was conducted to explore the pathogens community among patients with acute respiratory infection in a rural area in Senegal. A cross sectional study was conducted from August to December 2015. Children and adult patients attending Keur Socé health post for signs suggestive of acute respiratory infection were enrolled after providing inform consent. Eligible participants were recruited using a consecutive sampling method. Paired nose and throat swabs were collected for pathogen detection. Samples were processed using a multiplex PCR designed to identify 21 pathogens including both virus and bacteria. Two hundred and fifty patients participated in the study. Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus pneumoniae was the predominant pathogen (74%) and was present in all months and all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%). Respiratory syncytial virus (RSV) was detected only among children under 5 years old in August and September while coronavirus was present in all age groups, during the months of October and December. This pilot study revealed a diversity of pathogens over the time and across all age groups, highlighting the need for further exploration. A pathogen community approach including both virus and bacteria at a larger scale becomes crucial for a better understanding of transmission dynamics at population level in order to help shape ARI control strategies.

Background Seasonal malaria chemoprevention (SMC) using sulfadoxine–pyrimethamine plus amodiaquine has been introduced in 12 African countries. Additional strategies for safety monitoring are needed to supplement national systems of spontaneous reporting that are known to under represent the incidence of adverse reactions. Objectives This study aimed to determine if adverse event (AE) reporting could be improved using a smartphone application provided to village health workers, or by active follow-up using a symptom card provided to caregivers. Methods Two strategies to improve reporting of AEs during SMC campaigns were evaluated, in comparison with the national system of spontaneous reporting, in 11 health post areas in Senegal. In each health post, an average of approximately 4000 children under 10 years of age received SMC treatment each month for 3 months during the 2015 malaria transmission season—a total of 134,000 treatments. In three health posts (serving approximately 14,000 children), caregivers were encouraged to report any adverse reactions to the nurse at the health post or to a community health worker (CHW) in their village, who had been trained to use a smartphone application to report the event (enhanced spontaneous reporting). In two health posts (approximately 10,000 children), active follow-up of children at home was organized after each SMC campaign to ask about AEs that caregivers had been asked to record on a symptom card (active surveillance). Six health posts (approximately 23,000 children) followed the national system of spontaneous reporting using the national reporting (yellow) form. Each AE report was assessed by a panel to determine likely association with SMC drugs. Results The incidence of reported AEs was 2.4, 30.6, and 21.6 per 1000 children treated per month, using the national system, enhanced spontaneous reporting, and active surveillance, respectively. The most commonly reported symptoms were vomiting, fever, and abdominal pain. The incidence of vomiting, known to be caused by amodiaquine, was similar using both innovative methods (10/1000 in the first month, decreasing to 2.5/1000 in the third month). Despite increased surveillance, no serious adverse drug reactions were detected. Conclusion Training CHWs in each village and health facility staff to report AEs using a mobile phone application led to much higher reporting rates than through the national system. This approach is feasible and acceptable, and could be further improved by strengthening laboratory investigation and the collection of control data immediately prior to SMC campaigns.