Katharine Walter

All Publications

• Colonization of the tsetse fly midgut with commensal Kosakonia cowanii Zambiae inhibits trypanosome infection establishment. PLoS pathogens Weiss, B. L., Maltz, M. A., Vigneron, A., Wu, Y., Walter, K. S., O'Neill, M. B., Wang, J., Aksoy, S. 2019; 15 (2): e1007470

  Abstract

  Tsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infected animals and reducing tsetse population densities. However, relevant programs are costly, labor intensive and difficult to sustain. As such, novel strategies aimed at reducing tsetse vector competence require development. Herein we investigated whether Kosakonia cowanii Zambiae (Kco_Z), which confers Anopheles gambiae with resistance to Plasmodium, is able to colonize tsetse and induce a trypanosome refractory phenotype in the fly. Kco_Z established stable infections in tsetse's gut and exhibited no adverse effect on the fly's survival. Flies with established Kco_Z infections in their gut were significantly more refractory to infection with two distinct trypanosome species (T. congolense, 6% infection; T. brucei, 32% infection) than were age-matched flies that did not house the exogenous bacterium (T. congolense, 36% infected; T. brucei, 70% infected). Additionally, 52% of Kco_Z colonized tsetse survived infection with entomopathogenic Serratia marcescens, compared with only 9% of their wild-type counterparts. These parasite and pathogen refractory phenotypes result from the fact that Kco_Z acidifies tsetse's midgut environment, which inhibits trypanosome and Serratia growth and thus infection establishment. Finally, we determined that Kco_Z infection does not impact the fecundity of male or female tsetse, nor the ability of male flies to compete with their wild-type counterparts for mates. We propose that Kco_Z could be used as one component of an integrated strategy aimed at reducing the ability of tsetse to transmit pathogenic trypanosomes.

  View details for DOI 10.1371/journal.ppat.1007470

  View details for PubMedID 30817773

• Evaluating strategies for control of tuberculosis in prisons and prevention of spillover into communities: An observational and modeling study from Brazil. PLoS medicine Mabud, T. S., de Lourdes Delgado Alves, M., Ko, A. I., Basu, S., Walter, K. S., Cohen, T., Mathema, B., Colijn, C., Lemos, E., Croda, J., Andrews, J. R. 2019; 16 (1): e1002737

  Abstract

  It has been hypothesized that prisons serve as amplifiers of general tuberculosis (TB) epidemics, but there is a paucity of data on this phenomenon and the potential population-level effects of prison-focused interventions. This study (1) quantifies the TB risk for prisoners as they traverse incarceration and release, (2) mathematically models the impact of prison-based interventions on TB burden in the general population, and (3) generalizes this model to a wide range of epidemiological contexts.We obtained individual-level incarceration data for all inmates (n = 42,925) and all reported TB cases (n = 5,643) in the Brazilian state of Mato Grosso do Sul from 2007 through 2013. We matched individuals between prisoner and TB databases and estimated the incidence of TB from the time of incarceration and the time of prison release using Cox proportional hazards models. We identified 130 new TB cases diagnosed during incarceration and 170 among individuals released from prison. During imprisonment, TB rates increased from 111 cases per 100,000 person-years at entry to a maximum of 1,303 per 100,000 person-years at 5.2 years. At release, TB incidence was 229 per 100,000 person-years, which declined to 42 per 100,000 person-years (the average TB incidence in Brazil) after 7 years. We used these data to populate a compartmental model of TB transmission and incarceration to evaluate the effects of various prison-based interventions on the incidence of TB among prisoners and the general population. Annual mass TB screening within Brazilian prisons would reduce TB incidence in prisons by 47.4% (95% Bayesian credible interval [BCI], 44.4%-52.5%) and in the general population by 19.4% (95% BCI 17.9%-24.2%). A generalized model demonstrates that prison-based interventions would have maximum effectiveness in reducing community incidence in populations with a high concentration of TB in prisons and greater degrees of mixing between ex-prisoners and community members. Study limitations include our focus on a single Brazilian state and our retrospective use of administrative databases.Our findings suggest that the prison environment, more so than the prison population itself, drives TB incidence, and targeted interventions within prisons could have a substantial effect on the broader TB epidemic.

  View details for PubMedID 30677013

• Detection, survival and infectious potential of Mycobacterium tuberculosis in the environment: A review of the evidence and epidemiological implications. The European respiratory journal Martinez, L., Verma, R., Croda, J., Horsburgh, C. R., Walter, K. S., Degner, N., Middelkoop, K., Koch, A., Hermans, S., Warner, D., Wood, R., Cobelens, F., Andrews, J. R. 2019

  Abstract

  Much remains unknown about Mycobacterium tuberculosis transmission. Seminal experimental studies from the 1950s demonstrated that airborne expulsion of droplet nuclei from an infectious tuberculosis patient is the primary route of transmission. However, these findings did not rule out other routes of M. tuberculosis transmission. We reviewed historical scientific evidence from the late 19th and early 20th century and contemporary studies investigating the presence, persistence, and infectiousness of environmental M. tuberculosis We found evidence - both experimental and epidemiological - supporting the presence and viability of M. tuberculosis in multiple natural and built environments for months to years, presumably following contamination by a human source. Further, several studies confirm M. tuberculosis viability and virulence in the environment using guinea pig and mouse models. Most of this evidence was historical; however, several recent studies have reported consistent findings of M. tuberculosis detection and viability in the environment using modern methods. Whether or not M. tuberculosis in environments represents an infectious threat to humans, it may represent an untapped source of data with which to further understand M. tuberculosis transmission. We discuss potential opportunities for harnessing these data to generate new insights into tuberculosis transmission in congregate settings.

  View details for PubMedID 31048345

• Identifying climate drivers of infectious disease dynamics: recent advances and challenges ahead. Proceedings. Biological sciences Metcalf, C. J., Walter, K. S., Wesolowski, A., Buckee, C. O., Shevliakova, E., Tatem, A. J., Boos, W. R., Weinberger, D. M., Pitzer, V. E. 2017; 284 (1860)

  Abstract

  Climate change is likely to profoundly modulate the burden of infectious diseases. However, attributing health impacts to a changing climate requires being able to associate changes in infectious disease incidence with the potentially complex influences of climate. This aim is further complicated by nonlinear feedbacks inherent in the dynamics of many infections, driven by the processes of immunity and transmission. Here, we detail the mechanisms by which climate drivers can shape infectious disease incidence, from direct effects on vector life history to indirect effects on human susceptibility, and detail the scope of variation available with which to probe these mechanisms. We review approaches used to evaluate and quantify associations between climate and infectious disease incidence, discuss the array of data available to tackle this question, and detail remaining challenges in understanding the implications of climate change for infectious disease incidence. We point to areas where synthesis between approaches used in climate science and infectious disease biology provide potential for progress.

  View details for PubMedID 28814655

  View details for PubMedCentralID PMC5563806

• Genomic insights into the ancient spread of Lyme disease across North America. Nature ecology & evolution Walter, K. S., Carpi, G., Caccone, A., Diuk-Wasser, M. A. 2017; 1 (10): 1569–76

  Abstract

  Lyme disease is the most prevalent vector-borne disease in North America and continues to spread. The disease was first clinically described in the 1970s in Lyme, Connecticut, but the origins and history of spread of the Lyme disease bacteria, Borrelia burgdorferi sensu stricto (s.s.), are unknown. To explore the evolutionary history of B. burgdorferi in North America, we collected ticks from across the USA and southern Canada from 1984 to 2013 and sequenced the, to our knowledge, largest collection of 146 B. burgdorferi s.s. genomes. Here, we show that B. burgdorferi s.s. has a complex evolutionary history with previously undocumented levels of migration. Diversity is ancient and geographically widespread, well pre-dating the Lyme disease epidemic of the past ~40 years, as well as the Last Glacial Maximum ~20,000 years ago. This means the recent emergence of human Lyme disease probably reflects ecological change-climate change and land use changes over the past century-rather than evolutionary change of the bacterium.

  View details for PubMedID 29185509

  View details for PubMedCentralID PMC6431794

• Babesia microti from humans and ticks hold a genomic signature of strong population structure in the United States BMC GENOMICS Carpi, G., Walter, K. S., Ben Mamoun, C., Krause, P. J., Kitchen, A., Lepore, T. J., Dwivedi, A., Cornillot, E., Caccone, A., Diuk-Wasser, M. A. 2016; 17

  Abstract

  Babesia microti is an emerging tick-borne apicomplexan parasite with increasing geographic range and incidence in the United States. The rapid expansion of B. microti into its current distribution in the northeastern USA has been due to the range expansion of the tick vector, Ixodes scapularis, upon which the causative agent is dependent for transmission to humans.To reconstruct the history of B. microti in the continental USA and clarify the evolutionary origin of human strains, we used multiplexed hybrid capture of 25 B. microti isolates obtained from I. scapularis and human blood. Despite low genomic variation compared with other Apicomplexa, B. microti was strongly structured into three highly differentiated genetic clusters in the northeastern USA. Bayesian analyses of the apicoplast genomes suggest that the origin of the current diversity of B. microti in northeastern USA dates back 46 thousand years with a signature of recent population expansion in the last 1000 years. Human-derived samples belonged to two rarely intermixing clusters, raising the possibility of highly divergent infectious phenotypes in humans.Our results validate the multiplexed hybrid capture strategy for characterizing genome-wide diversity and relatedness of B. microti from ticks and humans. We find strong population structure in B. microti samples from the Northeast indicating potential barriers to gene flow.

  View details for DOI 10.1186/s12864-016-3225-x

  View details for Web of Science ID 000387183000009

  View details for PubMedID 27821055

• Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity PLOS PATHOGENS Walter, K. S., Carpi, G., Evans, B. R., Caccone, A., Diuk-Wasser, M. A. 2016; 12 (7)

  Abstract

  Hosts including humans, other vertebrates, and arthropods, are frequently infected with heterogeneous populations of pathogens. Within-host pathogen diversity has major implications for human health, epidemiology, and pathogen evolution. However, pathogen diversity within-hosts is difficult to characterize and little is known about the levels and sources of within-host diversity maintained in natural populations of disease vectors. Here, we examine genomic variation of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in 98 individual field-collected tick vectors as a model for study of within-host processes. Deep population sequencing reveals extensive and previously undocumented levels of Bb variation: the majority (~70%) of ticks harbor mixed strain infections, which we define as levels Bb diversity pre-existing in a diverse inoculum. Within-tick diversity is thus a sample of the variation present within vertebrate hosts. Within individual ticks, we detect signatures of positive selection. Genes most commonly under positive selection across ticks include those involved in dissemination in vertebrate hosts and evasion of the vertebrate immune complement. By focusing on tick-borne Bb, we show that vectors can serve as epidemiological and evolutionary sentinels: within-vector pathogen diversity can be a useful and unbiased way to survey circulating pathogen diversity and identify evolutionary processes occurring in natural transmission cycles.

  View details for DOI 10.1371/journal.ppat.1005759

  View details for Web of Science ID 000383366400039

  View details for PubMedID 27414806

• Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Walter, K. S., Pepin, K. M., Webb, C. T., Gaff, H. D., Krause, P. J., Pitzer, V. E., Diuk-Wasser, M. A. 2016; 283 (1832)

  Abstract

  Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach-occupancy modelling-to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease.

  View details for DOI 10.1098/rspb.2016.0834

  View details for Web of Science ID 000378318700023

  View details for PubMedID 27252022

• Whole genome capture of vector-borne pathogens from mixed DNA samples: a case study of Borrelia burgdorferi BMC GENOMICS Carpi, G., Walter, K. S., Bent, S. J., Hoen, A. G., Diuk-Wasser, M., Caccone, A. 2015; 16

  Abstract

  Rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. However, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen DNA.We addressed this challenge by using custom probes for multiplexed hybrid capture to enrich for and sequence 30 Borrelia burgdorferi genomes from field samples of its arthropod vector. Hybrid capture enabled sequencing of nearly the complete genome (~99.5 %) of the Borrelia burgdorferi pathogen with 132-fold coverage, and identification of up to 12,291 single nucleotide polymorphisms per genome.The proprosed culture-independent method enables efficient whole genome capture and sequencing of pathogens directly from arthropod vectors, thus making population genomic study of vector-borne and zoonotic infectious diseases economically feasible and scalable. Furthermore, given the similarities of invertebrate field specimens to other mixed DNA templates characterized by a high ratio of host to pathogen DNA, we discuss the potential applicabilty of hybrid capture for genomic study across diverse study systems.

  View details for DOI 10.1186/s12864-015-1634-x

  View details for Web of Science ID 000355967000001

  View details for PubMedID 26048573

• Microhabitat Partitioning of Aedes simpsoni (Diptera: Culicidae) JOURNAL OF MEDICAL ENTOMOLOGY Walter, K. S., Brown, J. E., Powell, J. R. 2014; 51 (3): 596-604

  Abstract

  Yellow fever virus is a reemerging infection responsible for widespread, sporadic outbreaks across Africa. Although Aedes aegypti (L.) is the most important vector globally, in East Africa, epidemics may be vectored by Aedes bromeliae (Theobald), a member of the Aedes simpsoni (Theobald) species complex. The Ae. simpsoni complex contains 10 subspecies, of which Ae. bromeliae alone has been incriminated as a vector of yellow fever virus. However, morphological markers cannot distinguish Ae. bromeliae from conspecifics, including the sympatric and non-anthropophilic Aedes lilii (Theobald). Here, we used three sequenced nuclear markers to examine the population structure of Ae. simpsoni complex mosquitoes collected from diverse habitats in Rabai, Kenya. Gene trees consistently show strong support for the existence of two clades in Rabai, with segregation by habitat. Domestic mosquitoes segregate separately from forest-collected mosquitoes, providing evidence of habitat partitioning on a small spatial scale (< 5 km). Although speculative, these likely represent what have been described as Ae. bromeliae and Ae. lilii, respectively. The observation of high levels of diversity within Rabai indicates that this species complex may exhibit significant genetic differentiation across East Africa. The genetic structure, ecology, and range of this important disease vector are surprisingly understudied and need to be further characterized.

  View details for DOI 10.1603/ME13097

  View details for Web of Science ID 000335660900013

  View details for PubMedID 24897852

• HLA Class I Subtype-Dependent Expansion of KIR3DS1(+) and KIR3DL1(+) NK Cells during Acute Human Immunodeficiency Virus Type 1 Infection JOURNAL OF VIROLOGY Alter, G., Rihn, S., Walter, K., Nolting, A., Martin, M., Rosenberg, E. S., Miller, J. S., Carrington, M., Altfeld, M. 2009; 83 (13): 6798-6805

  Abstract

  NK cells are critical in the early containment of viral infections. Epidemiological and functional studies have shown an important role of NK cells expressing specific killer immunoglobulin-like receptors (KIRs) in the control of human immunodeficiency virus type 1 (HIV-1) infection, but little is known about the mechanisms that determine the expansion of these antiviral NK cell populations during acute HIV-1 infection. Here we demonstrate that NK cells expressing the activating receptor KIR3DS1(+) and, to a lesser extent, the inhibitory receptor KIR3DL1(+) specifically expand in acute HIV-1 infection in the presence of HLA-B Bw480I, the putative HLA class I ligand for KIR3DL1/3DS1. These data demonstrate for the first time the HLA class I subtype-dependent expansion of specific KIR(+) NK cells during an acute viral infection in humans.

  View details for DOI 10.1128/JVI.00256-09

  View details for Web of Science ID 000267354100046

  View details for PubMedID 19386717

  View details for PubMedCentralID PMC2698561