David Saunders's research while affiliated with Uniformed Services University of the Health Sciences and other places
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Publications (94)
Background
Visceral leishmaniasis (VL) is a chronic protozoal disease caused from the bite of an infected sand fly. VL due to Leishmania infantum is endemic in Afghanistan, although its distribution is poorly characterized. The spectrum of VL ranges from asymptomatic to active VL with symptoms of fever, weight loss, organomegaly, and pancytopenia....
Background
The long-term duration of post COVID condition (PCC, “Long COVID”) remains unclear. In this study, we estimated the risk of healthcare encounters in Military Health System (MHS) beneficiaries for the 12 months post SARS-CoV-2 diagnosis, adjusting for prior healthcare use, and compared to those without known prior SARS-COV-2 diagnosis.
M...
Background
Predicting, preventing, and treating post-COVID condition (PCC; “Long COVID) is challenging due to a limited understanding of PCC mechanisms. To address this, we analyzed whole blood transcriptomic data using machine learning to identify candidate gene and gene expression pathways associated with the development of PCC.
Figure 1
(A) Clin...
Background
Prior studies suggest SARS-CoV-2 (SC2) infection and vaccination are risk factors for the development of Herpes Zoster (HZ). We performed a nested case-control study using data from the Epidemiology, Immunology and Clinical Characteristics of Emerging Infectious Diseases of Pandemic Potential (EPICC) cohort to evaluate the impact of SC2...
Background
Few studies have described cardiac sequela of SARS-CoV-2 infection in children across the spectrum of acute COVID-19 disease severity, particularly milder outpatient cases without multisystem inflammatory syndrome in children (MIS-C). We sought to define the frequency and long term outcomes of coronary artery aneurysms, depressed cardiac...
Background
We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections.
Methods
Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of ances...
Background
The long-term effects of COVID-19 on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain.
Methods
We compared survey responses in a one-year study of U.S. military service members with (n = 1923) and without (n = 1591) a history of SARS-CoV-2 infection. We fit Poisson regression models to estima...
Background: We sought to determine immune and behavioral pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections in a joint analysis of epidemiological and immunological cohort data.
Methods: Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were c...
Introduction:
Response to medications can differ widely among individual patients. Adverse drug reactions can lead to serious morbidity and mortality. Pharmacogenetic (PGx) testing can predict responses to medications and increased risks of adverse events where the genetic basis is understood. Several published manuscripts suggest positive impacts...
Background
SARS-CoV-2 most severely affects older age groups, while children experience minimal disease. We measured elements of adaptive immunity in children and adults with SARS-CoV-2 to define the age-dependent viral and host response.
Methods
Participants were enrolled in the Epidemiology, Immunology, and Clinical Characteristics of Emerging I...
Background
We sought to determine pre-infection correlates of immunity against SARS-CoV-2 post-vaccine infections.
Methods
Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of WT SARS...
Background: Significant clinical similarities have been observed between the recently described Long-Haul COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspne...
Background: Significant clinical similarities have been observed between the recently described ‘Long-Haul’ COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dysp...
Background:
New anti-malarial drugs are needed urgently to address the increasing challenges of drug-resistant falciparum malaria. Two rhinacanthin analogues containing a naphthoquinone moiety resembling atovaquone showed promising in-vitro activity against a P. falciparum laboratory reference strain (K1). The anti-malarial activity of these 2 com...
Background:
Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles.
Methods:
1,273 SARS-CoV-2 posi...
Importance
Understanding the factors associated with post-COVID conditions is important for prevention.
Objective
To identify characteristics associated with persistent post–COVID-19 symptoms and to describe post–COVID-19 medical encounters.
Design, Setting, and Participants
This cohort study used data from the Epidemiology, Immunology, and Clini...
We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot sample...
Background
Infection with SARS-CoV-2 and the resulting host immune response has been primarily characterized in middle and older aged populations due to a higher incidence of symptoms in these age groups. Due to reduced severity of disease, children were poorly studied and assumed to be less frequently infected compared to older age groups. We meas...
Background
Omicron SARS-CoV-2 infections are associated with less frequent olfactory sensory loss and a predominance of pharyngitis symptoms compared to prior variants, with proposed diagnostic implications. We examined whether such symptomology predicts a higher RNA abundance in the oropharynx. We further investigated how age, symptom-day, vaccina...
Background
COVID-19 may have deleterious effects on the fitness of active duty US military service members. We seek to understand the long-term functional consequences of SARS-CoV-2 infection in this critical population, and in other military healthcare beneficiaries.
Methods
The Epidemiology, Immunology, and Clinical Characteristics of Emerging I...
Background
We sought to determine the frequency of asymptomatic SARS-CoV-2 infections, the BNT162b2 mRNA COVID 19 vaccine-related symptoms, and the correlates of immunity in post-vaccination breakthrough infections in a prospective cohort of healthcare workers.
Methods
We have been conducting a single-center, observational cohort study of healthca...
The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with well-characterized single or multiple infection and/or vaccine exposures. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diver...
The rapid emergence of new SARS-CoV-2 variants challenges vaccination strategies. Here, we measured antigenic diversity among variants and interpreted neutralizing antibody responses following single and multiple exposures in longitudinal infection and vaccine cohorts. Antigenic cartography using primary infection antisera showed that BA.2, BA.4/BA...
The active metabolites of primaquine, in particular 5-hydroxyprimaquine, likely responsible for clearance of dormant hypnozoites, are produced through the hepatic CYP450 2D6 (CYP2D6) enzymatic pathway. With the inherent instability of 5-hydroxyprimaquine, a stable surrogate, 5,6 orthoquinone, can now be detected and measured in the urine as part of...
MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nuc...
MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nuc...
Background:
Influenza virus circulation is monitored through the Cambodian influenza-like illness (ILI) sentinel surveillance system and isolates are characterized by the National Influenza Centre (NIC). Seasonal influenza circulation has previously been characterized by year-round activity and a peak during the rainy season (June-November).
Obje...
Background
Malaria remains a critical public health problem in Southeast Asia despite intensive containment efforts. The continued spread of multi-drug-resistant Plasmodium falciparum has led to calls for malaria elimination on the Thai-Cambodian border. However, the optimal approach to elimination in difficult-to-reach border populations, such as...
Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether preval...
[This corrects the article DOI: 10.1371/journal.pone.0190418.].
Corrected versions of Tables 2–6.
(PDF)
Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein...
Genetic diversity of the R1 region in Block 3 of 163 3D7-liked msp2 sequences.
(PDF)
Frequencies of different sized msp2 variants determined by DNA sequencing (upper) and conventional gel electrophoresis (lower).
Sequence analysis differentiated msp2 variants into FC27 (red bars) or 3D7 (blue bars) families, respectively. The frequencies of variants sized by gel electrophoresis is shown by green bars in the lower panel.
(PDF)
Background
Emerging and re-emerging respiratory pathogens represent an increasing threat to public health. Etiological determination during outbreaks generally relies on clinical information, occasionally accompanied by traditional laboratory molecular or serological testing. Often, this limited testing leads to inconclusive findings.
The Armed For...
Despite rising resistance, dihydroartemisinin-piperaquine (DP) remains a first line therapy for uncomplicated malaria in many parts of Cambodia. While generally well-tolerated as a 3-day regimen, compressed 2-day regimens were associated with treatment-limiting cardiac repolarization effects in a recent clinical trial. To better estimate the risks...
Background
The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. Methods
Ex vivo parasite susceptibilities were tracked to determine the rate of...
Genomic epidemiology of artemisinin resistant malaria
MalariaGEN Plasmodium falciparum Community Project. Elife. 2016.
Free PMC article
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find...
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia
is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a
large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are
present at low frequency in Africa. We show that African kelch13 muta...
pH1N1 maximum likelihood phylogenetic trees for the MP segment for 15 samples from Cambodia (colored in blue) and references in Genbank (colored in black) collected in 2011 and 2012.
Vaccine strains are highlighted in red. Node support was calculated with aLRT and was >0.70 for all major nodes. All samples fell within the same major clade that incl...
Unique pH1N1 amino acid (AA) changes of unknown function in specific samples for the NA gene as compared to A/California/7/2009.
AA substitution nomenclature is as follows; reference amino acid (A/California/7/2009), amino acid site, sample amino acid. Amino acids are numbered from the start codon of the segment (ATG:Methionine).
(DOCX)
Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse trans...
pH1N1 maximum likelihood phylogenetic trees for the NA segment for 14 samples from Cambodia (colored in blue) and references in Genbank (colored in black) collected in 2011 and 2012 (also see main text Fig 1B).
Vaccine strains are highlighted in red. Node support was calculated with aLRT and was >0.70 for all major nodes. The 2011 samples fell with...
H3N2 average percent nucleotide sequence identity between vaccine strains and Cambodia isolates gene segments.
(DOCX)
Total number of viruses identified by pan-enteroviruses and rhinoviruses (EV/RV) PCR and nucleotide sequencing†
(DOCX)
Samples collected for genetic analysis in this study including virus subtype, sample origin, specimen type, sampling date and segments successfully sequenced.
(DOCX)
pH1N1 average percent nucleotide sequence identity between vaccine strains and Cambodia isolates gene segments.
(DOCX)
Primers for RT-PCR and nucleotide sequencing for EV/RV and EV71: The enterovirus 71 type specific primers were modified from the previous study by Singh et al. (2002) [53].
The modifications were made by following the alignments of VP1 sequences of different EV71 strains collected during 2002–2011 from Thailand, Taiwan, Philippines, Vietnam, and Ch...
Changes in glycosylation, antigenic and polymorphic sites linked to AA substitutions and sub-antigenic/catalytic sites (epitopes) where amino acid (AA) substitutions were found for for the HA and NA segments of pH1N1.
AA substitution nomenclature is as follows; reference amino acid (A/California/7/2009), amino acid site, sample amino acid. Amino ac...
Sequencing results of the EV71 isolates based on (A) pan rhinovirus/enterovirus inner primer and (B) Sequencing results of the EV71 isolates based on an enterovirus 71 inner primer.
(DOCX)
H3N2 sample amino acid substitution summary and selection analysis by group per segment analyzed.
(DOCX)
pH1N1 maximum likelihood phylogenetic trees for the NP segment for 15 samples from Cambodia (colored in blue) and references in Genbank (colored in black) collected in 2011 and 2012.
Vaccine strains are highlighted in red. Node support was calculated with aLRT and was >0.70 for all major nodes. The 2011 samples fell within the same clade and 2012 s...
Unique H3N2 amino acid changes of unknown function to specific to samples for the HA gene as compared to A/Victoria/361/2011.
AA substitution nomenclature is as follows; reference amino acid (A/Victoria/361/2011), amino acid site, sample amino acid. Amino acids are numbered from the start codon of the segment (ATG:Methionine).
(DOCX)
pH1N1 maximum likelihood phylogenetic trees for the NS segment for 15 samples from Cambodia (colored in blue) and references in Genbank (colored in black) collected in 2011 and 2012.
Vaccine strains are highlighted in red. Node support was calculated with aLRT and was >0.70 for all major nodes. The 2011 samples fell within the same clade and 2012 s...
pH1N1 maximum likelihood phylogenetic trees for the HA segment for 14 samples from Cambodia (colored in blue) and references in Genbank (colored in black) collected in 2011 and 2012 (also see main text Fig 1A).
Vaccine strains are highlighted in red. Node support was calculated with aLRT and was >0.70 for all major nodes. The 2011 samples fell with...
Unique H3N2 amino acid changes of unknown function to specific to samples for the NA gene as compared to A/Victoria/361/2011.
AA substitution nomenclature is as follows; reference amino acid (A/Victoria/361/2011), amino acid site, sample amino acid. Amino acids are numbered from the start codon of the segment (ATG:Methionine).
(DOCX)
Forward and reverse primers used in amplification of influenza viruses with 5' and 3' modifications indicated.
(DOCX)
pH1N1 sample amino acid substitution summary and selection analysis by group per segment analyzed.
(DOCX)
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 muta...
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelchl3 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 muta...
![FIG 4 Semi-log plots of means ( Ϯ standard deviations [SD]) of...](profile/Phisit-Khemawoot/publication/266324212/figure/fig4/AS:295778636582924@1447530530855/Semi-log-plots-of-means-standard-deviations-SD-of-concentration_Q320.jpg)
Primaquine (PQ) remains the sole available drug to prevent relapse of P. vivax malaria after more than 60 years. While administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential anti-relapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel easily scal...
Background
The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011.
Methodology/Principal Findings
Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from...
Background
Mirincamycin is a close analog of the drug clindamycin used to treat Plasmodium falciparum blood stages. The clinical need to treat Plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.
Methods
cis-mirinicamycin and trans-mirini...
Background: Little information is available about influenza and other common respiratory viruses in border populations in Western Cambodia, a region with relatively high incidence and highest mortality rate of H5N1 and future pandemic potential.
Methods: This out-patient surveillance system complements national surveillance using the same influen...
Dihydroartemisinin-piperaquine, the current first-line drug for uncomplicated P. falciparum and P. vivax in Cambodia, was shown previously to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly two-day treatment course in the Royal Cambodian Ar...
Emerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.
Efficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were com...
Despite recent malaria containment and control efforts leading to reduced incidence, Cambodia remains endemic for both Plasmodium vivax and multidrug-resistant Plasmodium falciparum malaria. Little has been reported in the peer-reviewed literature regarding the burden of severe malaria (SM) in Cambodia.
Medical records for all patients admitted to...
We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopul...
