The impact of COVID-19 on clinical research for Neglected Tropical Diseases (NTDs): A case study of bubonic plague

BackgroundAmong the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue.MethodsTo understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron’I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment.ResultsDuring the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases.DiscussionCOVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.     

Northern origin and diversification in the central lowlands? – Complex phylogeography and taxonomy of widespread day geckos (Phelsuma) from Madagascar

Day geckos of the Phelsuma lineata group are widespread in Madagascar and have been historically split into numerous species and subspecies based almost exclusively on differences in coloration and body size. We apply phylogenetic and phylogeographic methods to examine the biogeography and taxonomy of these lizards, including explicit tests of various biogeographic predictions and based on a molecular data set covering much of the distribution ranges of all species and subspecies of P. lineata, P. dorsivittata, P. comorensis, P. hoeschi, P. kely, and P. pusilla in Madagascar (and the Comoros archipelago for P. comorensis). Sequences of the mitochondrial 16S rRNA and the nuclear RAG-1 gene fragment were determined from 376 samples, and a multigene mtDNA phylogeny of the species group was constructed for the main phylogroups identified in the 16S haplotype network. We used the 16S sequences to estimate the geographic location of the ancestor of each major mtDNA clade and to infer their demographic history using a variety of statistical tools. Our phylogeny separates the taxa analyzed into two well-supported major subclades mainly occurring in the north respectively east of the island. Mismatch distribution of samples together with rejection of neutrality, the results of Bayesian Skyline Plots analysis, and a star-like network suggests a recent demographic expansion for the P. l. lineata lineage into the eastern lowlands, while the highland (P. l. elanthana) and northern clades (P. dorsivittata and P. l. punctulata) show signatures of rather stable populations. A major genetic discontinuity observed coincided with a northern lowland stretch that separates mid-altitude rainforests in the north from those in the center and south. Our analysis points to numerous unsolved taxonomic problems in this group of geckos, especially in the small-sized taxa (P. hoeschi, P. kely, P. pusilla), and provides a basis for a future comprehensive taxonomic revision, which will require integrative analysis of molecular, morphological and chromatic data as well as careful examination of type specimens.