Indoor residual spraying with a non-pyrethroid insecticide reduces the reservoir of Plasmodium falciparum in a high-transmission area in northern Ghana

Tiedje, Kathryn E.; Oduro, Abraham; Bangre, Oscar; Amenga-Etego, Lucas; Dadzie, Samuel; Appawu, Maxwell A.; Frempong, Kwadwo K.; Asoala, Victor; Ruybal‐Pesántez, Shazia; Narh, Charles A.; Deed, Samantha; Argyropoulos, Dionne C.; Ghansah, Anita; Agyei, Samuel A.; Segbaya, Sylvester; Desewu, Kwame; Williams, Ignatius; Simpson, Julie A; Malm, Keziah; Pascual, Mercedes; Koram, Kwadwo A.; Day, Karen P.

doi:10.1371/journal.pgph.0000285

Cited by 13 publications

(63 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…repertoire) of 45 var genes. The size of the repertoire was based on the median number of non-upsA DBLα sequences identified in our 3D7 laboratory isolate [22, 23]. This grouping of var genes is defined based on their semi-conserved upstream promoter sequences (ups) (i.e.…”

Section: Methodsmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted June 30, 2022. ; https://doi.org/10.1101/2022.06.27.497801 doi: bioRxiv preprint 0.05 which were estimated with MOI and the allele frequencies) [21,66]. Second, the MOI per host was also estimated from the simulated var genes data by counting the total number of distinct var genes within each host and by dividing it by the size of one repertoire, here 45 as estimated from control data using repeat samplings of the var genes of 3D7 with the varcoding protocol [23].…”

Section: Moi Estimationmentioning

confidence: 99%

“…Second, to account for var gene potential sampling errors, we applied a measurement model that sub-samples the number of var genes per strain, resulting in a reduction of the total number of var genes per host (Fig 2). This sub-sampling was implemented by exploring the distribution of the number of non-upsA DBLα var gene types per monoclonal infection for which molecular sequences were previously obtained during six cross-sectional surveys between 2012 and 2016 in the Bongo District in Ghana at the end of the wet season [22,23,36,59] (Fig 1D). For each strain, the number of var genes was sub-sampled according to a weight reflecting the var gene counts density function.…”

Section: Moi Estimationmentioning

confidence: 99%

“…Whole-genome sequencing is currently not a cost-effective approach when MOI is the main interest of a study, and these haplotype-reconstruction approaches are computationally intensive, resulting in limited MOI reliability for highly complex infections [20]. Finally, two cost-effective molecular approaches, known as THE REAL McCOIL [21] and var coding [22, 23], have been more recently developed to identify and track MOI with standard laboratory equipment. They differ in important ways as they rely on contrasting parts of the genome, respectively under neutrality and immune selection.…”

Section: Introductionmentioning

confidence: 99%

“…The more recent var coding approach (also termed var genotyping or var fingerprinting) [22, 23], employs the highly polymorphic sequences encoding the immunogenic DBLα domain of PfEMP1 ( Plasmodium falciparum erythrocyte membrane protein 1), the major surface antigen of the blood stage of infection [26]. During an infection, PfEMP1 molecules are exported by the parasite to the surface of the infected erythrocytes, where they influence virulence of the disease and become a target of the adaptive immune system [27].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Neutral vs. non-neutral genetic footprints of Plasmodium falciparum multiclonal infections

Labbé

Zhan

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

At a time when effective tools for monitoring malaria control and eradication efforts are crucial, the increasing availability of molecular data motivates their application to epidemiology. The multiplicity of infection (MOI), defined as the number of genetically distinct parasite strains co-infecting a host, is one key epidemiological parameter for evaluating malaria interventions. Estimating MOI remains a challenge for high-transmission settings where individuals typically carry multiple co-occurring infections. Several quantitative approaches have been developed to estimate MOI, including two cost-effective ones relying on molecular data: i) THE REAL McCOIL method is based on putatively neutral single nucleotide polymorphism loci, and ii) the varcoding method is a fingerprinting approach that relies on the diversity and limited repertoire overlap of the var multigene family encoding the major Plasmodium falciparum blood-stage antigen PfEMP1 and is therefore under selection. In this study, we assess the robustness of the MOI estimates generated with these two approaches by simulating P. falciparum malaria dynamics under three transmission conditions using an extension of a previously developed stochastic agent-based model. We demonstrate that these approaches are complementary and best considered across distinct transmission intensities. While varcoding can underestimate MOI, it allows robust estimation, especially under high-transmission where repertoire overlap is extremely limited from frequency-dependent selection. In contrast, THE REAL McCOIL often considerably overestimates MOI, but still provides reasonable estimates for low- and moderate-transmission. As many countries pursue malaria elimination targets, defining the most suitable approach to estimate MOI based on sample size and local transmission intensity is highly recommended for monitoring the impact of intervention programs.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Moi Estimationmentioning

confidence: 99%

Section: Moi Estimationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neutral vs. non-neutral genetic footprints of Plasmodium falciparum multiclonal infections

Labbé

Zhan

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Measuring changes inPlasmodium falciparumcensus population size in response to sequential malaria control interventions

Tiedje

Zhan

Ruybal‐Pesántez

et al. 2023

Preprint

View full text Add to dashboard Cite

The diversity of Plasmodium falciparum within human hosts requires parasite population size be defined in terms of parasite variation rather than the number of infected hosts. To calculate census population size, we rely on a definition of parasite variation known as multiplicity of infection (MOIvar), defined by the hyper-diversity of the var multigene family. We present a Bayesian approach to estimate MOIvar based on sequencing and counting the number of unique DBLα tags (or DBLα types) of var genes, taking into consideration measurement error, and derive from it census population size or the total number of distinct infections of relevance to transmission events. We track changes in parasite population size and structure, using MOIvar, from baseline and through sequential malaria interventions by indoor residual spraying (IRS) and seasonal malaria chemoprevention (SMC) in an area characterized by high-seasonal malaria transmission in northern Ghana. Var DBLα tag sequencing was completed on asymptomatic P. falciparum isolates at baseline (2012), during IRS (2014), post-IRS (2015) and during SMC (2017) from ~2,000 individuals of all ages surveyed at each time point. Following IRS, which reduced transmission intensity by > 90% and decreased parasite prevalence by ~40-50%, significant reductions in var diversity, MOIvar, and population size were observed across all ages. These changes, consistent with the loss of diverse parasite genomes, were short lived and 32-months after IRS was discontinued and SMC was introduced, var diversity and population size rebounded in all age groups except for the younger children (1-5 years) targeted by SMC. By measuring population size in this way, we show that despite major perturbations, the parasite population remained very large and retained the var population genetic characteristics of a high-transmission system (high var diversity; low var repertoire similarity) demonstrating the resilience of P. falciparum to short-term interventions in high-burden countries of sub-Saharan Africa.

show abstract

A paradoxical population structure ofvarDBLα types in Africa

Tan,

Tiedje,

Feng

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Thevarmultigene family encodes theP. falciparumerythrocyte membrane protein 1 (PfEMP1), which is important in host-parasite interaction as a virulence factor and major surface antigen of the blood stages of the parasite, responsible for maintaining chronic infection. Whilst important in the biology ofP. falciparum, these genes (50 to 60 genes per parasite genome) are routinely excluded from whole genome analyses due to their hyper-diversity, achieved primarily through recombination. The PfEMP1 head structure almost always consists of a DBLα-CIDR tandem. Categorised into different groups (upsA, upsB, upsC), different head structures have been associated with different ligand-binding affinities and disease severities. We study how conserved individual DBLα types are at the country, regional, and local scales in Sub-Saharan Africa. Using publicly-available sequence datasets and a novel ups classification algorithm,cUps, we performed anin silicoexploration of DBLα conservation through time and space in Africa. In all three ups groups, the population structure of DBLα types in Africa consists of variants occurring at rare, low, moderate, and high frequencies. Non-rare variants were found to be temporally stable in a local area in endemic Ghana. When inspected across different geographical scales, we report different levels of conservation; while some DBLα types were consistently found in high frequencies in multiple African countries, others were conserved only locally, signifying local preservation of specific types. Underlying this population pattern is the composition of DBLα types within each isolate DBLα repertoire, revealed to also consist of a mix of types found at rare, low, moderate, and high frequencies in the population. We further discuss the adaptive forces and balancing selection, including host genetic factors, potentially shaping the evolution and diversity of DBLα types in Africa.

show abstract

Indoor residual spraying with a non-pyrethroid insecticide reduces the reservoir of Plasmodium falciparum in a high-transmission area in northern Ghana

Cited by 13 publications

References 37 publications

Neutral vs. non-neutral genetic footprints of Plasmodium falciparum multiclonal infections

Neutral vs. non-neutral genetic footprints of Plasmodium falciparum multiclonal infections

Measuring changes inPlasmodium falciparumcensus population size in response to sequential malaria control interventions

A paradoxical population structure ofvarDBLα types in Africa

Contact Info

Product

Resources

About