A5041301752- Malaria Research and Control
- Mosquito-borne diseases and control
- Vector-borne infectious diseases
- Chromosomal and Genetic Variations
- vaccines and immunoinformatics approaches
- Parasites and Host Interactions
- Insect symbiosis and bacterial influences
- Trypanosoma species research and implications
- HIV Research and Treatment
- Complement system in diseases
- Invertebrate Immune Response Mechanisms
- Genomics and Phylogenetic Studies
- Hepatitis B Virus Studies
- Antibiotic Resistance in Bacteria
- Parasite Biology and Host Interactions
- Microbial infections and disease research
- Hepatitis C virus research
- Genetics, Bioinformatics, and Biomedical Research
- Aquaculture disease management and microbiota
- Molecular Biology Techniques and Applications
- HIV/AIDS drug development and treatment
- Hemoglobinopathies and Related Disorders
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- Glycosylation and Glycoproteins Research
University of California, San Francisco
2024-2025
Brown University
2025
Providence College
2025
University of Massachusetts Chan Medical School
2015-2024
University of North Carolina at Chapel Hill
2024
UMass Memorial Medical Center
2023
University of Massachusetts Boston
2020
University of Massachusetts Amherst
2020
ABSTRACT Ixodes scapularis is the principal vector of Lyme disease on East Coast and in upper Midwest regions United States, yet tick also present Southeast, where absent or rare. A closely related species, I. affinis , carries pathogen South but does not seem to transmit it humans. In order better understand geographic diversity tick, we analyzed microbiota 104 adult 13 ticks captured 19 locations Carolina, North Virginia, Connecticut, New York. Initially, from 4 sites were by 454...
In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium parasites lacking (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether deletions confer sufficient selective advantage to drive population expansion. By studying blood samples from a cohort of 12,572 participants enroled in prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan South using PCR, an...
PCR amplicon deep sequencing continues to transform the investigation of genetic diversity in viral, bacterial, and eukaryotic populations. In populations such as Plasmodium falciparum infections, it is important discriminate sequences differing by a single nucleotide polymorphism. bacterial populations, single-base resolution can provide improved towards species strains. Here, we introduce SeekDeep suite built around qluster algorithm, which capable accurately building de novo clusters...
Abstract The Democratic Republic of the Congo (DRC) harbors 11% global malaria cases, yet little is known about spatial and genetic structure parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative sample from DRC samples surrounding countries, using molecular inversion probes - high-throughput genotyping tool. identify an east-west divide haplotypes to confer resistance chloroquine sulfadoxine-pyrimethamine. Furthermore,...
Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection males compared to females. To test the hypothesis that sex-based differences host-parasite interactions affect epidemiology malaria, we intensively followed Plasmodium falciparum infections cohort endemic area eastern Uganda and estimated both force (FOI) rate clearance using amplicon deep-sequencing. We found no evidence behavioral risk factors, or FOI by sex. In contrast, females cleared...
CRISPR-based diagnostics are a new class of highly sensitive and specific assays with multiple applications in infectious disease diagnosis. SHERLOCK, or Specific High-Sensitivity Enzymatic Reporter UnLOCKing, is one such diagnostic that combines recombinase polymerase pre-amplification, CRISPR-RNA base-pairing, LwCas13a activity for nucleic acid detection.
Targeted amplicon sequencing is a powerful and efficient tool for interrogating the Plasmodium falciparum genome, generating actionable data from infections to complement traditional malaria epidemiology. For maximum impact, genomic tools should be multi-purpose, robust, sensitive, reproducible. We developed, characterized, implemented MAD4HatTeR, an panel based on Multiplex Amplicons Drug, Diagnostic, Diversity, Differentiation Haplotypes using Resequencing, along with bioinformatic...
Plasmodium vivax infections often recur due to relapse of hypnozoites from the liver. In malaria-endemic areas, tools distinguish reinfection are needed. We applied amplicon deep sequencing P. isolates 78 Cambodian volunteers, nearly one-third whom suffered recurrence at a median 68 days. Deep highly variable region merozoite surface protein 1 gene revealed impressive diversity-generating 67 unique haplotypes and detecting on average 3.6 cocirculating parasite clones within individuals,...
Abstract Background Targeted next-generation sequencing offers the potential for consistent, deep coverage of information-rich genomic regions to characterize polyclonal Plasmodium falciparum infections. However, methods identify and sequence these are currently limited. Methods A bioinformatic pipeline multiplex were developed simultaneously 100 targets applied dried blood spot (DBS) controls field isolates from Mozambique. For comparison, whole-genome data generated same controls. Results...
Abstract Mozambique is one of the four African countries which account for over half all malaria deaths worldwide, yet little known about parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected 2015 2018 seven provinces to genotype antimalarial resistance markers interrogate population using genome-wide microhaplotyes. Here we show only resistance-associated observed at frequencies above 5%...
Abstract Targeted amplicon sequencing is a powerful and efficient tool to interrogate the P . falciparum genome generate actionable data from infections complement traditional malaria epidemiology. For maximum impact, genomic tools should be multi-purpose, robust, sensitive reproducible. We developed, characterized, implemented MAD 4 HatTeR, an panel based on Multiplex Amplicons for Drug, Diagnostic, Diversity, Differentiation Haplotypes using Resequencing, along with bioinformatic pipeline...
Humans living in regions with high falciparum malaria transmission intensity harbour multi-strain infections comprised of several genetically distinct haplotypes. The number parasite haplotypes identified from an infected human host at a given time is referred to as the complexity infection (COI). In this study, amplicon-based deep sequencing method targeting Plasmodium apical membrane antigen 1 (pfama1) was utilized (1) investigate relationship between P. prevalence and COI, (2) explore...
Current tools struggle to detect drug-resistant malaria parasites when infections contain multiple parasite clones, which is the norm in high transmission settings Africa. Our aim was develop and apply an approach for detecting resistance that overcomes challenges of polyclonal without requiring a genetic marker resistance.Clinical samples from patients treated with artemisinin combination therapy were collected Tanzania Cambodia. By deeply sequencing hypervariable locus, we quantified...
Although Plasmodium vivax is a leading cause of malaria around the world, only handful antigens are being studied for vaccine development. Here, we investigated genetic signatures selection and geospatial diversity two – merozoite surface protein 1 (pvmsp-1) circumsporozoite (pvcsp). Using scalable next-generation sequencing, deep-sequenced amplicons 42 kDa region pvmsp-1 (n = 44) complete gene pvcsp 47) from Cambodian isolates. These sequences were then compared with global parasite...
A key drawback to monitoring the emergence and spread of antimalarial drug resistance in sub-Saharan Africa is early detection containment. Next-generation sequencing methods offer resolution, sensitivity, scale required fill this gap by surveilling for molecular markers resistance. We performed targeted using inversion probes interrogate five Plasmodium falciparum genes ( pfcrt , pfmdr1 pfdhps pfdhfr pfk13 ) implicated chloroquine, sulfadoxine-pyrimethamine (SP), artemisinin two sites Ghana.
Most malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and PfHRP3, but deletions of pfhrp2 phfrp3 genes make parasites undetectable by RDTs. We analyzed 19,313 public whole-genome-sequenced P. field samples to understand these better. Pfhrp2 deletion only occurred chromosomal breakage with subsequent telomere healing. Pfhrp3 involved loss from pfhrp3 the showed three patterns: no other associated rearrangement evidence healing at breakpoint...
Abstract Molecular methods to understand host feeding patterns of arthropod vectors are critical assess exposure risk vector‐borne disease and unveil complex ecological interactions. We build on our prior work discovering the utility PCR‐Sanger sequencing blood meal analysis that well for soft ticks (Acari: Argasidae), unlike hard Ixodidae), thanks their unique physiology retains meals years. Here, we apply metabarcoding using amplicon deep identify multiple species in individual...
Malaria in pregnancy (MiP) remains a major public health challenge areas of high malaria transmission. Intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent the adverse consequences MiP. The effectiveness SP for IPTp may be reduced where dhps581 mutation (a key marker level resistance) found; this was previously reported common Tanga Region northern Tanzania, but there are limited data from other areas. frequency molecular markers resistance...
Abstract Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental is mediated by P. protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity impact on clinical remain poorly understood. Through amplicon deep-sequencing placental samples from women Malawi Benin, we assessed sequence VAR2CSA’s ID1-DBL2x region, containing putative targets estimated associations...
Abstract Knowledge of host associations blood-feeding vectors may afford insights into managing disease systems and protecting public health. However, the ability methods to distinguish bloodmeal sources varies widely. We used two methods—Sanger sequencing amplicon deep sequencing—to target a 228 bp region vertebrate Cytochrome b gene determine hosts fed upon by triatomines (n = 115) collected primarily in Texas, USA. Direct Sanger PCR amplicons was successful for 36 samples (31%). revealed...
In the thirteen years since first report of pfhrp2-deleted parasites in 2010, World Health Organization (WHO) has found that 40 47 countries surveyed worldwide have reported pfhrp2/3 gene deletions. Due to a high prevalence deletions causing false-negative HRP2 RDTs, last five years, Eritrea, Djibouti and Ethiopia switched or started switching using alternative target pan-specific-pLDH P. falciparum specific-pLDH alone combination with HRP2. However, manufacturing RDTs not been brought scale...
Human immunodeficiency virus 1 (HIV-1) risk groups include, but are not limited to, heterosexual individuals (HET), men-who-have-sex-with-men (MSM), and people who inject drugs (PWID). Although genetically diverse HIV-1 populations transferred from donor to recipient, systemic infection is often established by a single clone, the transmitted/founder (T/F) virus. This phenomenon especially prevalent in sexual transmission, less stringent blood-to-blood contact transmission. Specific traits...
Genotyping Plasmodium falciparum subpopulations in malaria infections is an important aspect of molecular epidemiology to understand within-host diversity and the frequency drug resistance markers. We characterized P. genetic asymptomatic subsequent first febrile using amplicon sequencing (AmpSeq) ama1 Coastal Kenya. also examined temporal changes haplotype frequencies mdr1, a drug-resistant marker. found >60% were polyclonal (complexity infection [COI] >1) there was reduction COI over time....
Major advances in Plasmodium sequencing approaches, bioinformatic pipelines, and data analysis tools have provided valuable insights into malaria epidemiology from parasite genomic data. However, translating genetic actionable information for decision-makers remains a challenge. Significant barriers limit the integration of these functional ecosystem that produces standardized, interpretable results use by national control programs. The Genomic Epidemiology (PlasmoGenEpi) network convened 18...
The Democratic Republic of the Congo (DRC) bears a high burden malaria, which is exacerbated in pregnant women. VAR2CSA protein plays crucial role pregnancy-associated malaria (PAM), and hence quantifying diversity at var2csa locus DRC important understanding basic epidemiology PAM, developing robust vaccine against PAM.Samples were taken from 2013-14 Demographic Health Survey conducted DRC, focusing on children under 5 years age. A short subregion gene was sequenced 115 spatial clusters,...