Nicholas J. Hathaway
University of Massachusetts Medical School
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Featured researches published by Nicholas J. Hathaway.
Applied and Environmental Microbiology | 2015
Will Van Treuren; Loganathan Ponnusamy; R Jory Brinkerhoff; Antonio González; Christian M. Parobek; Jonathan J. Juliano; Theodore G. Andreadis; Richard C. Falco; Lorenza Beati Ziegler; Nicholas J. Hathaway; Corinna Keeler; Michael Emch; Jeffrey A. Bailey; R. Michael Roe; Rob Knight; Steven R. Meshnick
ABSTRACT Ixodes scapularis is the principal vector of Lyme disease on the East Coast and in the upper Midwest regions of the United States, yet the tick is also present in the Southeast, where Lyme disease is absent or rare. A closely related species, I. affinis, also carries the pathogen in the South but does not seem to transmit it to humans. In order to better understand the geographic diversity of the tick, we analyzed the microbiota of 104 adult I. scapularis and 13 adult I. affinis ticks captured in 19 locations in South Carolina, North Carolina, Virginia, Connecticut, and New York. Initially, ticks from 4 sites were analyzed by 454 pyrosequencing. Subsequently, ticks from these sites plus 15 others were analyzed by sequencing with an Illumina MiSeq machine. By both analyses, the microbiomes of female ticks were significantly less diverse than those of male ticks. The dissimilarity between tick microbiomes increased with distance between sites, and the state in which a tick was collected could be inferred from its microbiota. The genus Rickettsia was prominent in all locations. Borrelia was also present in most locations and was present at especially high levels in one site in western Virginia. In contrast, members of the family Enterobacteriaceae were very common in North Carolina I. scapularis ticks but uncommon in I. scapularis ticks from other sites and in North Carolina I. affinis ticks. These data suggest substantial variations in the Ixodes microbiota in association with geography, species, and sex.
The Journal of Infectious Diseases | 2015
Jessica T. Lin; Nicholas J. Hathaway; David L. Saunders; Chanthap Lon; Sujata Balasubramanian; Oksana Kharabora; Panita Gosi; Sabaithip Sriwichai; Laurel Kartchner; Char Meng Chuor; Prom Satharath; Charlotte A. Lanteri; Jeffrey A. Bailey; Jonathan J. Juliano
Plasmodium vivax infections often recur due to relapse of hypnozoites from the liver. In malaria-endemic areas, tools to distinguish relapse from reinfection are needed. We applied amplicon deep sequencing to P. vivax isolates from 78 Cambodian volunteers, nearly one-third of whom suffered recurrence at a median of 68 days. Deep sequencing at a highly variable region of the P. vivax merozoite surface protein 1 gene revealed impressive diversity-generating 67 unique haplotypes and detecting on average 3.6 cocirculating parasite clones within individuals, compared to 2.1 clones detected by a combination of 3 microsatellite markers. This diversity enabled a scheme to classify over half of recurrences as probable relapses based on the low probability of reinfection by multiple recurring variants. In areas of high P. vivax diversity, targeted deep sequencing can help detect genetic signatures of relapse, key to evaluating antivivax interventions and achieving a better understanding of relapse-reinfection epidemiology.
PLOS Neglected Tropical Diseases | 2014
Christian M. Parobek; Jeffrey A. Bailey; Nicholas J. Hathaway; Duong Socheat; William O. Rogers; Jonathan J. Juliano
Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens – Plasmodium vivax merozoite surface protein 1 (pvmsp-1) and Plasmodium vivax circumsporozoite protein (pvcsp). Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44) and the complete gene of pvcsp (n = 47) from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines.
Evolution, medicine, and public health | 2016
Nicole Mideo; Jeffrey A. Bailey; Nicholas J. Hathaway; Billy Ngasala; David L. Saunders; Chanthap Lon; Oksana Kharabora; Andrew Jamnik; Sujata Balasubramanian; Anders Björkman; Andreas Mårtensson; Steven R. Meshnick; Andrew F. Read; Jonathan J. Juliano
Our approach for detecting drug resistance identifies rare resistant parasites in polyclonal infections through their phenotypic signature. By translating genetic data to clearance phenotypes of parasite subpopulations in malaria infections, we found rare slow clearing parasites in Tanzania where resistance to front-line drugs is not thought to be a problem.
Nucleic Acids Research | 2018
Nicholas J. Hathaway; Christian M. Parobek; Jonathan J. Juliano; Jeffrey A. Bailey
Abstract PCR amplicon deep sequencing continues to transform the investigation of genetic diversity in viral, bacterial, and eukaryotic populations. In eukaryotic populations such as Plasmodium falciparum infections, it is important to discriminate sequences differing by a single nucleotide polymorphism. In bacterial populations, single-base resolution can provide improved resolution towards species and strains. Here, we introduce the SeekDeep suite built around the qluster algorithm, which is capable of accurately building de novo clusters representing true, biological local haplotypes differing by just a single base. It outperforms current software, particularly at low frequencies and at low input read depths, whether resolving single-base differences or traditional OTUs. SeekDeep is open source and works with all major sequencing technologies, making it broadly useful in a wide variety of applications of amplicon deep sequencing to extract accurate and maximal biologic information.
Scientific Reports | 2017
Jaymin C. Patel; Nicholas J. Hathaway; Christian M. Parobek; Kyaw Lay Thwai; Mwayiwawo Madanitsa; Carole Khairallah; Linda Kalilani-Phiri; Victor Mwapasa; Achille Massougbodji; Nadine Fievet; Jeffery A. Bailey; Feiko O. ter Kuile; Philippe Deloron; Stephanie M. Engel; Steve M. Taylor; Jonathan J. Juliano; Nicaise Tuikue Ndam; Steven R. Meshnick
Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA’s ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes. Overall, var2csa diversity was high and haplotypes subdivided into five clades, the largest two defined by homology to parasites strains, 3D7 or FCR3. Across both cohorts, compared to women infected with only FCR3-like variants, women infected with only 3D7-like variants delivered infants with lower birthweight (difference: −267.99 g; 95% Confidence Interval [CI]: −466.43 g,−69.55 g) and higher odds of low birthweight (<2500 g) (Odds Ratio [OR] 5.41; 95% CI:0.99,29.52) and small-for-gestational-age (OR: 3.65; 95% CI: 1.01,13.38). In two distinct malaria-endemic African settings, parasites harboring 3D7-like variants of VAR2CSA were associated with worse birth outcomes, supporting differential effects of infection with specific parasite strains. The immense diversity coupled with differential clinical effects of this diversity suggest that an effective VAR2CSA-based vaccine may require multivalent activity.
American Journal of Tropical Medicine and Hygiene | 2018
Andreea Waltmann; Achille Massougbodji; Steven R. Meshnick; Jonathan J. Juliano; Christian M. Parobek; Nicaise Tuikue Ndam; Nicholas J. Hathaway; Kyaw Lay Thwai; Philippe Deloron; Jeffery A. Bailey; Nadine Fievet; Jaymin C. Patel
In pregnancy-associated malaria, infected erythrocytes accumulate in the placenta. It is unclear if in polyclonal infections this results in distinct peripheral and placental parasite populations. We used long amplicon deep sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral and placental samples collected at delivery from a high transmission area to determine genetic homology. Despite substantial sequence variation and detecting 23 haplotypes, the matched pairs mostly contained the same genetic variants, with 11 pairs sharing 100% of their variants, whereas others showed some heterogeneity. Thus, at delivery, peripheral and placental parasites appear to intermix and placental genotypes can be inferred through peripheral sampling.
Malaria Journal | 2017
Jeremiah Ngondi; Deus S. Ishengoma; Stephanie M. Doctor; Kyaw Lay Thwai; Corinna Keeler; Sigsbert Mkude; Oresto M. Munishi; Ritha Willilo; Shabbir Lalji; Naomi Kaspar; Chonge Kitojo; Lynn A. Paxton; Nicholas J. Hathaway; Jeffrey A. Bailey; Jonathan J. Juliano; Steven R. Meshnick; Julie Gutman
American Journal of Tropical Medicine and Hygiene | 2016
Nicholas F. Brazeau; Nicholas J. Hathaway; Christian M. Parobek; Jessica T. Lin; Jeffrey A. Bailey; Chanthap Lon; David L. Saunders; Jonathan J. Juliano
Malaria Journal | 2017
Robin H. Miller; Nicholas J. Hathaway; Oksana Kharabora; Kashamuka Mwandagalirwa; Antoinette Tshefu; Steven R. Meshnick; Steve M. Taylor; Jonathan J. Juliano; V. Ann Stewart; Jeffrey A. Bailey