Search

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 Kunzs 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.

• Over 50% of parasites considered in this study harboured the mutant C 72 I 74 E 75 T 76 haplotype of the Pfcrt gene. • As it stands, CQ cannot be re-introduced as treatment for malaria in Nigeria if ACT resistance were to emerge. • 21.1% of parasites had the Pfmdr- 1 mutant N 86 F 184 haplotype in Nigeria which suggests an increase in prevalence. • The three ACTs considered in this study, i.e. AA, AL and DHP, are still effective antimalarials with DHP slightly superior. The emergence and spread of Plasmodium falciparum parasites resistant to artemisinin derivatives and their partners in southeastern Asia threatens malaria control and elimination efforts, and heightens the need for an alternative therapy. We have explored the distribution of P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr- 1) haplotypes 10 years following adoption of artemisinin-based combination therapies in a bid to investigate the possible re-emergence of Chloroquine-sensitive parasites in Nigeria, and investigated the effect of these P. falciparum haplotypes on treatment outcomes of patients treated with artemisinin-based combination therapies. A total of 271 children aged <5 years with uncomplicated falciparum malaria were included in this study. Polymorphisms on codons 72–76 of the Pfcrt gene and codon 86 and 184 of Pfmdr -1 were determined using the high resolution melting assay. Of 240 (88.6%) samples successfully genotyped with HRM for Pfcrt , wildtype C 72 M 74 N 75 K 76 (42.9%) and mutant C 72 I 74 E 75 T 76 (53.8%) were observed. Also, wildtype N 86 Y 184 (62.9%) and mutant N 86 F 184 (21.1%), Y 86 Y 184 (6.4%), and Y 86 F 184 (0.4%) haplotypes of Pfmdr -1 were observed. Measures of responsiveness to ACTs were similar in children infected with P. falciparum crt haplotypes (C 72 I 74 E 75 T 76 and C 72 M 74 N 75 K 76) and major mdr -1 haplotypes (N 86 Y 184 , N 86 F 184 and Y 86 Y 184). Despite a 10 year gap since the malaria treatment policy changed to ACTs, over 50% of the P. falciparum parasites investigated in this study harboured the Chloroquine-resistant C 72 I 74 E 75 T 76 haplotype, however this did not compromise the efficacy of artemisinin-based combination therapies. Should complete artemisinin resistance emerge from or spread to Nigeria, chloroquine might not be a good alternative therapy. [ABSTRACT FROM AUTHOR]