Publications by authors named "Matthew R Kasper"

42 Publications

An Outbreak of Covid-19 on an Aircraft Carrier. Reply.

N Engl J Med 2021 03 10;384(10):976-977. Epub 2021 Feb 10.

Navy and Marine Corps Public Health Center, Portsmouth, VA.

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http://dx.doi.org/10.1056/NEJMc2034424DOI Listing
March 2021

An Outbreak of Covid-19 on an Aircraft Carrier.

N Engl J Med 2020 12 11;383(25):2417-2426. Epub 2020 Nov 11.

From the U.S. Navy Bureau of Medicine and Surgery, Falls Church (M.R.K., B.L.G.), and the Navy and Marine Corps Public Health Center, Portsmouth (J.R.G., A.J.R., T.L., A.M.V.T., G.D., R.J.H.) - both in Virginia; U.S. Navy Seventh Fleet, Yokosuka, Japan (C.L.S.); U.S. Pacific Fleet, Pearl Harbor, Hawaii (M.B.M.); the U.S. Naval Hospital Guam, Apra Harbor (N.O., D.H., R.F.); and the Uniformed Services University of the Health Sciences, Bethesda (T.H.B.), and the Naval Medical Research Center, Silver Spring (A.W.A.) - both in Maryland.

Background: An outbreak of coronavirus disease 2019 (Covid-19) occurred on the U.S.S. , a nuclear-powered aircraft carrier with a crew of 4779 personnel.

Methods: We obtained clinical and demographic data for all crew members, including results of testing by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). All crew members were followed up for a minimum of 10 weeks, regardless of test results or the absence of symptoms.

Results: The crew was predominantly young (mean age, 27 years) and was in general good health, meeting U.S. Navy standards for sea duty. Over the course of the outbreak, 1271 crew members (26.6% of the crew) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by rRT-PCR testing, and more than 1000 infections were identified within 5 weeks after the first laboratory-confirmed infection. An additional 60 crew members had suspected Covid-19 (i.e., illness that met Council of State and Territorial Epidemiologists clinical criteria for Covid-19 without a positive test result). Among the crew members with laboratory-confirmed infection, 76.9% (978 of 1271) had no symptoms at the time that they tested positive and 55.0% had symptoms develop at any time during the clinical course. Among the 1331 crew members with suspected or confirmed Covid-19, 23 (1.7%) were hospitalized, 4 (0.3%) received intensive care, and 1 died. Crew members who worked in confined spaces appeared more likely to become infected.

Conclusions: SARS-CoV-2 spread quickly among the crew of the U.S.S. . Transmission was facilitated by close-quarters conditions and by asymptomatic and presymptomatic infected crew members. Nearly half of those who tested positive for the virus never had symptoms.
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http://dx.doi.org/10.1056/NEJMoa2019375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675688PMC
December 2020

Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study.

Int J Mol Sci 2020 Aug 18;21(16). Epub 2020 Aug 18.

US Naval Research Laboratory, Center for Biomolecular Science & Engineering, Washington, DC 20375, USA.

Infectious diarrhea affects over four billion individuals annually and causes over a million deaths each year. Though not typically prescribed for treatment of uncomplicated diarrheal disease, antimicrobials serve as a critical part of the armamentarium used to treat severe or persistent cases. Due to widespread over- and misuse of antimicrobials, there has been an alarming increase in global resistance, for which a standardized methodology for geographic surveillance would be highly beneficial. To demonstrate that a standardized methodology could be used to provide molecular surveillance of antimicrobial resistance (AMR) genes, we initiated a pilot study to test 130 diarrheal pathogens ( spp., , , and spp.) from the USA, Peru, Egypt, Cambodia, and Kenya for the presence/absence of over 200 AMR determinants. We detected a total of 55 different determinants conferring resistance to ten different categories of antimicrobials: genes detected in ≥ 25 samples included , (A), (B), (A), (B), , , , , , Δ1, , and . The number of determinants per strain ranged from none (several spp. strains) to sixteen, with isolates from Egypt harboring a wider variety and greater number of genes per isolate than other sites. Two samples harbored carbapenemase genes, or . Genes conferring resistance to azithromycin ((A), (A)/(K), (B)), a first-line therapeutic for severe diarrhea, were detected in over 10% of all Enterobacteriaceae tested: these included >25% of the Enterobacteriaceae from Egypt and Kenya. Forty-six percent of the Egyptian Enterobacteriaceae harbored genes encoding CTX-M-1 or CTX-M-9 families of extended-spectrum β-lactamases. Overall, the data provide cross-comparable resistome information to establish regional trends in support of international surveillance activities and potentially guide geospatially informed medical care.
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http://dx.doi.org/10.3390/ijms21165928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460656PMC
August 2020

Serotype Distribution of Clinical Isolates before the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Cambodia.

Am J Trop Med Hyg 2018 03 4;98(3):791-796. Epub 2018 Jan 4.

Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

Childhood vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Cambodia in January 2015. Baseline data regarding circulating serotypes are scarce. All microbiology laboratories in Cambodia were contacted for identification of stored isolates of from clinical specimens taken before the introduction of PCV13. Available isolates were serotyped using a multiplex polymerase chain reaction method. Among 166 identified isolates available for serotyping from patients with pneumococcal disease, 4% were isolated from upper respiratory samples and 80% were from lower respiratory samples, and 16% were invasive isolates. PCV13 serotypes accounted for 60% (95% confidence interval [CI] 52-67) of all isolates; 56% (95% CI 48-64) of noninvasive and 77% (95% CI 57-89) of invasive isolates. Antibiotic resistance was more common among PCV13 serotypes. This study of clinical isolates supports the potential for high reduction in pneumococcal disease burden and may serve as baseline data for future monitoring of serotypes circulation after implementation of PCV13 childhood vaccination in Cambodia.
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http://dx.doi.org/10.4269/ajtmh.17-0692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930902PMC
March 2018

Use of Bibliometric Analysis to Assess the Scientific Productivity and Impact of the Global Emerging Infections Surveillance and Response System Program, 2006-2012.

Mil Med 2017 05;182(5):e1749-e1756

Armed Forces Health Surveillance Center, 11800 Tech Road No. 200, Silver Spring, MD 20904.

Background: Scientific publication in academic literature is a key venue in which the U.S. Department of Defense's Global Emerging Infections Surveillance and Response System (GEIS) program disseminates infectious disease surveillance data. Bibliometric analyses are tools to evaluate scientific productivity and impact of published research, yet are not routinely used for disease surveillance. Our objective was to incorporate bibliometric indicators to measure scientific productivity and impact of GEIS-funded infectious disease surveillance, and assess their utility in the management of the GEIS surveillance program.

Methods: Metrics on GEIS program scientific publications, project funding, and countries of collaborating institutions from project years 2006 to 2012 were abstracted from annual reports and program databases and organized by the six surveillance priority focus areas: respiratory infections, gastrointestinal infections, febrile and vector-borne infections, antimicrobial resistance, sexually transmitted infections, and capacity building and outbreak response. Scientific productivity was defined as the number of scientific publications in peer-reviewed literature derived from GEIS-funded projects. Impact was defined as the number of citations of a GEIS-funded publication by other peer-reviewed publications, and the Thomson Reuters 2-year journal impact factor. Indicators were retrieved from the Web of Science and Journal Citation Report. To determine the global network of international collaborations between GEIS partners, countries were organized by the locations of collaborating institutions.

Results: Between 2006 and 2012, GEIS distributed approximately US $330 million to support 921 total projects. On average, GEIS funded 132 projects (range 96-160) with $47 million (range $43 million-$53 million), annually. The predominant surveillance focus areas were respiratory infections with 317 (34.4%) projects and $225 million, and febrile and vector-borne infections with 274 (29.8%) projects and $45 million. The number of annual respiratory infections-related projects peaked in 2006 and 2009. The number of febrile and vector-borne infections projects increased from 29 projects in 2006 to 58 in 2012. There were 651 articles published in 147 different peer-reviewed journals, with an average Thomson Reuters 2-year journal impact factor of 4.2 (range 0.3-53.5). On average, 93 articles were published per year (range 67-117) with $510,000 per publication. Febrile and vector-borne, respiratory, and gastrointestinal infections had 287, 167, and 73 articles published, respectively. Of the 651 articles published, 585 (89.9%) articles were cited at least once (range 1-1,045). Institutions from 90 countries located in all six World Health Organization regions collaborated with surveillance projects.

Conclusions: These findings summarize the GEIS-funded surveillance portfolio between 2006 and 2012, and demonstrate the scientific productivity and impact of the program in each of the six disease surveillance priority focus areas. GEIS might benefit from further financial investment in both the febrile and vector-borne and sexually transmitted infections surveillance priority focus areas and increasing peer-reviewed publications of surveillance data derived from respiratory infections projects. Bibliometric indicators are useful to measure scientific productivity and impact in surveillance systems; and this methodology can be utilized as a management tool to assess future changes to GEIS surveillance priorities. Additional metrics should be developed when peer-reviewed literature is not used to disseminate noteworthy accomplishments.
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http://dx.doi.org/10.7205/MILMED-D-16-00276DOI Listing
May 2017

Burden of Influenza in 4 Ecologically Distinct Regions of Peru: Household Active Surveillance of a Community Cohort, 2009-2015.

Clin Infect Dis 2017 Oct;65(9):1532-1541

US Naval Medical Research Unit No. 6, Bellavista, Peru.

Background: There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators.

Methods: We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction.

Results: We followed participants for 35353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged ≥65 years.

Conclusions: Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs.
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http://dx.doi.org/10.1093/cid/cix565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850002PMC
October 2017

Incidence of Norovirus-Associated Diarrhea and Vomiting Disease Among Children and Adults in a Community Cohort in the Peruvian Amazon Basin.

Clin Infect Dis 2017 Sep;65(5):833-839

Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.

Background: Data on norovirus epidemiology among all ages in community settings are scarce, especially from tropical settings.

Methods: We implemented active surveillance in 297 households in Peru from October 2012 to August 2015 to assess the burden of diarrhea and acute gastroenteritis (AGE) due to norovirus in a lower-middle-income community. During period 1 (October 2012-May 2013), we used a "traditional" diarrhea case definition (≥3 loose/liquid stools within 24 hours). During period 2 (June 2013-August 2015), we used an expanded case definition of AGE (by adding ≥2 vomiting episodes without diarrhea or 1-2 vomiting episodes plus 1-2 loose/liquid stools within 24 hours). Stool samples were tested for norovirus by reverse-transcription polymerase chain reaction.

Results: During period 1, overall diarrhea and norovirus-associated diarrhea incidence was 37.2/100 person-years (PY) (95% confidence interval [CI], 33.2-41.7) and 5.7/100 PY (95% CI, 3.9-8.1), respectively. During period 2, overall AGE and norovirus-associated AGE incidence was 51.8/100 PY (95% CI, 48.8-54.9) and 6.5/100 PY (95% CI, 5.4-7.8), respectively. In both periods, children aged <2 years had the highest incidence of norovirus. Vomiting without diarrhea occurred among norovirus cases in participants <15 years old, but with a higher proportion among children <2 years, accounting for 35% (7/20) of all cases in this age group. Noroviruses were identified in 7% (23/335) of controls free of gastroenteric symptoms.

Conclusions: Norovirus was a significant cause of AGE in this community, especially among children <2 years of age. Inclusion of vomiting in the case definition resulted in a 20% improvement for detection of norovirus cases.
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http://dx.doi.org/10.1093/cid/cix423DOI Listing
September 2017

Whole-Genome Analysis of Bartonella ancashensis, a Novel Pathogen Causing Verruga Peruana, Rural Ancash Region, Peru.

Emerg Infect Dis 2017 03;23(3):430-438

The genus Bartonella contains >40 species, and an increasing number of these Bartonella species are being implicated in human disease. One such pathogen is Bartonella ancashensis, which was isolated in blood samples from 2 patients living in Caraz, Peru, during a clinical trial of treatment for bartonellosis. Three B. ancashensis strains were analyzed by using whole-genome restriction mapping and high-throughput pyrosequencing. Genome-wide comparative analysis of Bartonella species showed that B. ancashensis has features seen in modern and ancient lineages of Bartonella species and is more related to B. bacilliformis. The divergence between B. ancashensis and B. bacilliformis is much greater than what is seen between known Bartonella genetic lineages. In addition, B. ancashensis contains type IV secretion system proteins, which are not present in B. bacilliformis. Whole-genome analysis indicates that B. ancashensis might represent a distinct Bartonella lineage phylogenetically related to B. bacilliformis.
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http://dx.doi.org/10.3201/eid2303.161476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382735PMC
March 2017

Complete Genome Sequences of Five Zika Virus Isolates.

Genome Announc 2016 May 12;4(3). Epub 2016 May 12.

Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA

Zika virus is an emerging human pathogen of great concern due to putative links to microcephaly and Guillain-Barre syndrome. Here, we report the complete genomes, including the 5' and 3' untranslated regions, of five Zika virus isolates, one from the Asian lineage and four from the African lineage.
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http://dx.doi.org/10.1128/genomeA.00377-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866861PMC
May 2016

The Genetic Diversity of Influenza A Viruses in Wild Birds in Peru.

PLoS One 2016 19;11(1):e0146059. Epub 2016 Jan 19.

Virology and Emerging Infections Department, United States Naval Medical Research Unit No. 6, Callao, Peru.

Our understanding of the global ecology of avian influenza A viruses (AIVs) is impeded by historically low levels of viral surveillance in Latin America. Through sampling and whole-genome sequencing of 31 AIVs from wild birds in Peru, we identified 10 HA subtypes (H1-H4, H6-H7, H10-H13) and 8 NA subtypes (N1-N3, N5-N9). The majority of Peruvian AIVs were closely related to AIVs found in North America. However, unusual reassortants, including a H13 virus containing a PA segment related to extremely divergent Argentinian viruses, suggest that substantial AIV diversity circulates undetected throughout South America.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146059PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718589PMC
July 2016

Full Genomic Characterization of a Saffold Virus Isolated in Peru.

Pathogens 2015 Nov 20;4(4):816-25. Epub 2015 Nov 20.

Naval Medical Research Unit No. 6 (NAMRU-6), Callao 2, Peru.

While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.
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http://dx.doi.org/10.3390/pathogens4040816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693166PMC
November 2015

A population-based estimate of the economic burden of influenza in Peru, 2009-2010.

Influenza Other Respir Viruses 2016 07 29;10(4):301-9. Epub 2016 Jan 29.

U.S. Naval Medical Research Unit No. 6, Callao, Peru.

Introduction: Influenza disease burden and economic impact data are needed to assess the potential value of interventions. Such information is limited from resource-limited settings. We therefore studied the cost of influenza in Peru.

Methods: We used data collected during June 2009-December 2010 from laboratory-confirmed influenza cases identified through a household cohort in Peru. We determined the self-reported direct and indirect costs of self-treatment, outpatient care, emergency ward care, and hospitalizations through standardized questionnaires. We recorded costs accrued 15-day from illness onset. Direct costs represented medication, consultation, diagnostic fees, and health-related expenses such as transportation and phone calls. Indirect costs represented lost productivity during days of illness by both cases and caregivers. We estimated the annual economic cost and the impact of a case of influenza on a household.

Results: There were 1321 confirmed influenza cases, of which 47% sought health care. Participants with confirmed influenza illness paid a median of $13 [interquartile range (IQR) 5-26] for self-treatment, $19 (IQR 9-34) for ambulatory non-medical attended illness, $29 (IQR 14-51) for ambulatory medical attended illness, and $171 (IQR 113-258) for hospitalizations. Overall, the projected national cost of an influenza illness was $83-$85 millions. Costs per influenza illness represented 14% of the monthly household income of the lowest income quartile (compared to 3% of the highest quartile).

Conclusion: Influenza virus infection causes an important economic burden, particularly among the poorest families and those hospitalized. Prevention strategies such as annual influenza vaccination program targeting SAGE population at risk could reduce the overall economic impact of seasonal influenza.
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http://dx.doi.org/10.1111/irv.12357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910177PMC
July 2016

Complete Genome Sequence of Bartonella ancashensis Strain 20.00, Isolated from the Blood of a Patient with Verruga Peruana.

Genome Announc 2015 Nov 5;3(6). Epub 2015 Nov 5.

Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Here we present the complete genome sequence of Bartonella ancashensis strain 20.00, isolated from the blood of a Peruvian patient with verruga peruana, known as Carrion's disease. Bartonella ancashensis is a Gram-negative bacillus, phylogenetically most similar to Bartonella bacilliformis, the causative agent of Oroya fever and verruga peruana.
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http://dx.doi.org/10.1128/genomeA.01217-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645191PMC
November 2015

Wide distribution and ancient evolutionary history of simian foamy viruses in New World primates.

Retrovirology 2015 Oct 29;12:89. Epub 2015 Oct 29.

Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd., MS G-45, Atlanta, GA, 30329, USA.

Background: Although simian foamy viruses (SFV) are the only exogenous retroviruses to infect New World monkeys (NWMs), little is known about their evolutionary history and epidemiology. Previous reports show distinct SFVs among NWMs but were limited to small numbers of captive or wild monkeys from five (Cebus, Saimiri, Ateles, Alouatta, and Callithrix) of the 15 NWM genera. Other studies also used only PCR testing or serological assays with limited validation and may have missed infection in some species. We developed and validated new serological and PCR assays to determine the prevalence of SFV in blood specimens from a large number of captive NWMs in the US (n = 274) and in captive and wild-caught NWMs (n = 236) in Peruvian zoos, rescue centers, and illegal trade markets. Phylogenetic and co-speciation reconciliation analyses of new SFV polymerase (pol) and host mitochondrial cytochrome B sequences, were performed to infer SFV and host co-evolutionary histories.

Results: 124/274 (45.2 %) of NWMs captive in the US and 59/157 (37.5 %) of captive and wild-caught NWMs in Peru were SFV WB-positive representing 11 different genera (Alouatta, Aotus, Ateles, Cacajao, Callithrix, Cebus, Lagothrix, Leontopithecus, Pithecia, Saguinus and Saimiri). Seroprevalences were lower at rescue centers (10/53, 18.9 %) compared to zoos (46/97, 47.4 %) and illegal trade markets (3/7, 8/19, 42.9 %) in Peru. Analyses showed that the trees of NWM hosts and SFVs have remarkably similar topologies at the level of species and sub-populations suggestive of co-speciation. Phylogenetic reconciliation confirmed 12 co-speciation events (p < 0.002) which was further supported by obtaining highly similar divergence dates for SFV and host genera and correlated SFV-host branch times. However, four ancient cross-genus transmission events were also inferred for Pitheciinae to Atelidae, Cacajao to ancestral Callithrix or Cebus monkeys, between Callithrix and Cebus monkeys, and Lagothrix to Alouatta.

Conclusions: We demonstrate a broad distribution and stable co-speciation history of SFV in NWMs at the species level. Additional studies are necessary to further explore the epidemiology and natural history of SFV infection of NWMs and to determine the zoonotic potential for persons exposed to infected monkeys in captivity and in the wild.
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http://dx.doi.org/10.1186/s12977-015-0214-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627628PMC
October 2015

Description of Bartonella ancashensis sp. nov., isolated from the blood of two patients with verruga peruana.

Int J Syst Evol Microbiol 2015 Oct;65(10):3339-3343

Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Three novel isolates of the genus Bartonella were recovered from the blood of two patients enrolled in a clinical trial for the treatment of chronic stage Bartonella bacilliformis infection (verruga peruana) in Caraz, Ancash, Peru. The isolates were initially characterized by sequencing a fragment of the gltA gene, and found to be disparate from B. bacilliformis. The isolates were further characterized using phenotypic and genotypic methods, and found to be genetically identical to each other for the genes assessed, but distinct from any known species of the genus Bartonella, including the closest relative B. bacilliformis. Other characteristics of the isolates, including their morphology, microscopic and biochemical properties, and growth patterns, were consistent with members of the genus Bartonella. Based on these results, we conclude that these three isolates are members of a novel species of the genus Bartonella for which we propose the name Bartonella ancashensis sp. nov. (type strain 20.00T = ATCC BAA-2694T = DSM 29364T).
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http://dx.doi.org/10.1099/ijsem.0.000416DOI Listing
October 2015

Detection of Mycobacterium tuberculosis Complex in New World Monkeys in Peru.

Ecohealth 2015 Jun 17;12(2):288-97. Epub 2014 Dec 17.

Washington National Primate Research Center, University of Washington, 1705 Pacific St NE, HSB I-039, Box 357330, Seattle, WA, 98105, USA.

The Mycobacterium tuberculosis complex causes tuberculosis in humans and nonhuman primates and is a global public health concern. Standard diagnostics rely upon host immune responses to detect infection in nonhuman primates and lack sensitivity and specificity across the spectrum of mycobacterial infection in these species. We have previously shown that the Oral Swab PCR (OSP) assay, a direct pathogen detection method, can identify the presence of M. tuberculosis complex in laboratory and free-ranging Old World monkeys. Addressing the current limitations in tuberculosis diagnostics in primates, including sample acquisition and pathogen detection, this paper furthers our understanding of the presence of the tuberculosis-causing bacteria among New World monkeys in close contact with humans. Here we use the minimally invasive OSP assay, which includes buccal swab collection followed by amplification of the IS6110 repetitive nucleic acid sequence specific to M. tuberculosis complex subspecies, to detect the bacteria in the mouths of Peruvian New World monkeys. A total of 220 buccal swabs from 16 species were obtained and positive amplification of the IS6110 sequence was observed in 30 (13.6%) of the samples. To our knowledge, this is the first documentation of M. tuberculosis complex DNA in a diverse sample of Peruvian Neotropical primates.
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http://dx.doi.org/10.1007/s10393-014-0996-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470872PMC
June 2015

Little evidence of subclinical avian influenza virus infections among rural villagers in Cambodia.

PLoS One 2014 12;9(5):e97097. Epub 2014 May 12.

Naval Medical Research Center-Asia/National Institute of Public Health, Phnom Penh, Cambodia.

In 2008, 800 adults living within rural Kampong Cham Province, Cambodia were enrolled in a prospective cohort study of zoonotic influenza transmission. After enrollment, participants were contacted weekly for 24 months to identify acute influenza-like illnesses (ILI). Follow-up sera were collected at 12 and 24 months. A transmission substudy was also conducted among the family contacts of cohort members reporting ILI who were influenza A positive. Samples were assessed using serological or molecular techniques looking for evidence of infection with human and avian influenza viruses. Over 24 months, 438 ILI investigations among 284 cohort members were conducted. One cohort member was hospitalized with a H5N1 highly pathogenic avian influenza (HPAI) virus infection and withdrew from the study. Ninety-seven ILI cases (22.1%) were identified as influenza A virus infections by real-time RT-PCR; none yielded evidence for AIV. During the 2 years of follow-up, 21 participants (3.0%) had detectable antibody titers (≥ 1:10) against the studied AIVs: 1 against an avian-like A/Migratory duck/Hong Kong/MPS180/2003(H4N6), 3 against an avian-like A/Teal/Hong Kong/w312/97(H6N1), 9 (3 of which had detectible antibody titers at both 12- and 24-month follow-up) against an avian-like A/Hong Kong/1073/1999(H9N2), 6 (1 detected at both 12- and 24-month follow-up) against an avian-like A/Duck/Memphis/546/74(H11N9), and 2 against an avian-like A/Duck/Alberta/60/76(H12N5). With the exception of the one hospitalized cohort member with H5N1 infection, no other symptomatic avian influenza infections were detected among the cohort. Serological evidence for subclinical infections was sparse with only one subject showing a 4-fold rise in microneutralization titer over time against AvH12N5. In summary, despite conducting this closely monitored cohort study in a region enzootic for H5N1 HPAI, we were unable to detect subclinical avian influenza infections, suggesting either that these infections are rare or that our assays are insensitive at detecting them.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097097PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018260PMC
June 2015

Molecular typing of "Candidatus Bartonella ancashi," a new human pathogen causing verruga peruana.

J Clin Microbiol 2013 Nov 28;51(11):3865-8. Epub 2013 Aug 28.

Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

A recently described clinical isolate, "Candidatus Bartonella ancashi," was obtained from a blood sample of a patient presenting with verruga peruana in the Ancash region of Peru. This sample and a second isolate obtained 60 days later from the same patient were molecularly typed using multilocus sequence typing (MLST) and multispacer sequence typing (MST). The isolates were 100% indistinguishable from each other but phylogenetically distant from Bartonella bacilliformis and considerably divergent from other known Bartonella species, confirming their novelty.
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http://dx.doi.org/10.1128/JCM.01226-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889784PMC
November 2013

Outbreak of Group A beta hemolytic Streptococcus pharyngitis in a Peruvian military facility, April 2012.

MSMR 2013 Jun;20(6):14-7

Emerging Infections Department, U.S. Naval Medical Research Unit No. 6, Lima, Peru.

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a common cause of acute pharyngitis as well as other diseases. Closed populations such as those living on military bases, nursing homes, and prisons are particularly vulnerable to GAS outbreaks due to crowding that facilitates person-to-person transmission. This report details a large outbreak of GAS pharyngitis at a Peruvian military training facility near Lima, Peru, in April 2012. Initial findings showed 145 cases. However, as the investigation continued it was revealed that some trainees may have concealed their illness to avoid real or perceived negative consequences of seeking medical care. A subsequent anonymous survey of all trainees revealed at least 383 cases of pharyngitis among the facility's 1,549 trainees and an attack rate of 34 percent among the 1,137 respondents. The epidemic curve revealed a pattern consistent with routine person-to-person transmission, although a point-source initiating event could not be excluded. Laboratory results showed GAS emm type 80.1 to be the culprit pathogen, an organism not commonly implicated in outbreaks of GAS in the Americas. Barious unique and illustrative features of outbreak investigation in military facilities and populations are discussed.
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June 2013

Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia.

J Infect Public Health 2013 Apr 1;6(2):69-79. Epub 2013 Feb 1.

Naval Medical Research Unit #2/National Institute of Public Health, Phnom Penh, Cambodia.

Background: Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur.

Methods: In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI) virus transmission where highly pathogenic avian influenza (HPAI) H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains.

Results: Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1). However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2), validated with a monoclonal antibody blocking ELISA assay specific for avian H9.

Conclusions: Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2) virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia.
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http://dx.doi.org/10.1016/j.jiph.2012.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612269PMC
April 2013

Outbreak of gastrointestinal illness during Operation New Horizons in Pisco, Peru, July 2012.

MSMR 2012 Nov;19(11):17-9

U.S. Naval Medical Research Unit No. 6, Lima, Peru.

In July 2012, the U.S. Naval Medical Research Unit No. 6 investigated an outbreak of gastrointestinal illness characterized by diarrhea among U.S. service members participating in Operation New Horizons in Pisco, Peru. Overall, there were 25 cases of self-reported diarrheal illness among 101 respondents to a questionnaire (attack rate: 24.8%). Personnel who consumed food that was prepared at the two hotels where they were lodged were more likely to report diarrhea than those who did not eat at the hotels (40.9% [9/22] versus 20.3% [16/79]; RR=2.1; p=.047). The difference in diarrhea attack rates between lodgers at the two hotels was not statistically significant. Known or putative pathogens were identified in 72.7 percent (8/11) of samples tested: Blastocystis hominis, Shigella sonnei, diffusely adherent Escherichia coli, and norovirus genotypes I and II. The investigation's findings suggested a food-borne etiology from hotel kitchens. Among all personnel, hand-washing hygiene was reinforced; however, food sources were not restricted.
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November 2012

Diarrhea outbreak during U.S. military training in El Salvador.

PLoS One 2012 18;7(7):e40404. Epub 2012 Jul 18.

U.S. Naval Medical Research Unit 6, Lima, Peru.

Infectious diarrhea remains a major risk to deployed military units worldwide in addition to their impact on travelers and populations living in the developing world. This report describes an outbreak of diarrheal illness in the U.S. military's 130(th) Maneuver Enhancement Brigade deployed in San Vicente, El Salvador during a training and humanitarian assistance mission. An outbreak investigation team from U.S. Naval Medical Research Unit-Six conducted an epidemiologic survey and environmental assessment, patient interviews, and collected stool samples for analysis in an at risk population of 287 personnel from May 31(st) to June 3(rd), 2011. Personnel (n = 241) completed an epidemiological survey (87% response rate) and 67 (27%) reported diarrhea and/or vomiting during the past two weeks. The median duration of illness was reported to be 3 days (IQR 2-4 days) and abdominal pain was reported among 30 (49%) individuals. Presentation to the medical aid station was sought by (62%) individuals and 9 (15%) had to stop or significantly reduce work for at least one day. Microscopy and PCR analysis of 14 stool samples collected from previously symptomatic patients, Shigella (7), Cryptosporidium (5), and Cyclospora (4) were the most prevalent pathogens detected. Consumption of food from on-base local vendors (RR = 4.01, 95% CI = 1.53-10.5, p-value <0.001) and arriving on base within the past two weeks (RR = 2.79, 95% confidence [CI] = 1.35-5.76, p-value = 0.001) were associated with increased risk of developing diarrheal disease. The risk of infectious diarrhea is great among reserve military personnel during two week training exercises. The consumption of local food, prepared without proper monitoring, is a risk factor for deployed personnel developing diarrheal illness. Additional information is needed to better understand disease risks to personnel conducting humanitarian assistance activities in the Latin America Region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040404PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399860PMC
March 2013

Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage.

PLoS Negl Trop Dis 2012 28;6(2):e1477. Epub 2012 Feb 28.

Institute for Human Infections and Immunity, Center for Tropical Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.

Background: Zika virus (ZIKV) is a mosquito-borne flavivirus distributed throughout much of Africa and Asia. Infection with the virus may cause acute febrile illness that clinically resembles dengue fever. A recent study indicated the existence of three geographically distinct viral lineages; however this analysis utilized only a single viral gene. Although ZIKV has been known to circulate in both Africa and Asia since at least the 1950s, little is known about the genetic relationships between geographically distinct virus strains. Moreover, the geographic origin of the strains responsible for the epidemic that occurred on Yap Island, Federated States of Micronesia in 2007, and a 2010 pediatric case in Cambodia, has not been determined.

Methodology/principal Findings: To elucidate the genetic relationships of geographically distinct ZIKV strains and the origin of the strains responsible for the 2007 outbreak on Yap Island and a 2010 Cambodian pediatric case of ZIKV infection, the nucleotide sequences of the open reading frame of five isolates from Cambodia, Malaysia, Nigeria, Uganda, and Senegal collected between 1947 and 2010 were determined. Phylogenetic analyses of these and previously published ZIKV sequences revealed the existence of two main virus lineages (African and Asian) and that the strain responsible for the Yap epidemic and the Cambodian case most likely originated in Southeast Asia. Examination of the nucleotide and amino acid sequence alignments revealed the loss of a potential glycosylation site in some of the virus strains, which may correlate with the passage history of the virus.

Conclusions/significance: The basal position of the ZIKV strain isolated in Malaysia in 1966 suggests that the recent outbreak in Micronesia was initiated by a strain from Southeast Asia. Because ZIKV infection in humans produces an illness clinically similar to dengue fever and many other tropical infectious diseases, it is likely greatly misdiagnosed and underreported.
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http://dx.doi.org/10.1371/journal.pntd.0001477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289602PMC
June 2012

Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia.

Am J Trop Med Hyg 2012 Feb;86(2):246-253

The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations.
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http://dx.doi.org/10.4269/ajtmh.2012.11-0409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269275PMC
February 2012

Short report: Rapid-test based identification of influenza as an etiology of acute febrile illness in Cambodia.

Am J Trop Med Hyg 2011 Dec;85(6):1144-5

U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia.

Influenza can be manifested as an acute febrile illness, with symptoms similar to many pathogens endemic to Cambodia. The objective of this study was to evaluate the Quickvue influenza A+B rapid test to identify the etiology of acute febrile illness in Cambodia. During December 2006-May 2008, patients enrolled in a study to identify the etiology of acute febrile illnesses were tested for influenza by real-time reverse transcriptase PCR (RT-PCR) and Quickvue influenza A+B rapid test. The prevalence of influenza was 19.7% by RT-PCR. Compared with RT-PCR, the sensitivity and specificity of the rapid test were 52.1% and 92.5%, respectively. The influenza rapid test identified the etiology in 10.2% of enrollees and ≥ 35% during peak times of influenza activity. This study suggests that rapid influenza tests may be useful during peak times of influenza activity in an area where several different etiologies can present as an acute febrile illness.
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http://dx.doi.org/10.4269/ajtmh.2011.11-0390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225168PMC
December 2011

Dual infection of novel influenza viruses A/H1N1 and A/H3N2 in a cluster of Cambodian patients.

Am J Trop Med Hyg 2011 Nov;85(5):961-3

Naval Health Research Center, San Diego, California, USA.

During the early months of 2009, a novel influenza A/H1N1 virus (pH1N1) emerged in Mexico and quickly spread across the globe. In October 2009, a 23-year-old male residing in central Cambodia was diagnosed with pH1N1. Subsequently, a cluster of four influenza-like illness cases developed involving three children who resided in his home and the children's school teacher. Base composition analysis of internal genes using reverse transcriptase polymerase chain reaction and electrospray ionization mass spectrometry revealed that specimens from two of the secondary victims were coinfected with influenza A/H3N2 and pH1N1. Phylogenetic analysis of the hemagglutinin genes from these isolated viruses showed that they were closely related to existing pH1N1 and A/H3N2 viruses circulating in the region. Genetic recombination was not evident within plaque-purified viral isolates on full genome sequencing. This incident confirms dual influenza virus infections and highlights the risk of zoonotic and seasonal influenza viruses to coinfect and possibly, reassort where they cocirculate.
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http://dx.doi.org/10.4269/ajtmh.2011.11-0098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205650PMC
November 2011

Enteric disease surveillance under the AFHSC-GEIS: current efforts, landscape analysis and vision forward.

BMC Public Health 2011 Mar 4;11 Suppl 2:S7. Epub 2011 Mar 4.

Armed Forces Health Surveillance Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.

The mission of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) is to support global public health and to counter infectious disease threats to the United States Armed Forces, including newly identified agents or those increasing in incidence. Enteric diseases are a growing threat to U.S. forces, which must be ready to deploy to austere environments where the risk of exposure to enteropathogens may be significant and where routine prevention efforts may be impractical. In this report, the authors review the recent activities of AFHSC-GEIS partner laboratories in regards to enteric disease surveillance, prevention and response. Each partner identified recent accomplishments, including support for regional networks. AFHSC/GEIS partners also completed a Strengths, Weaknesses, Opportunities and Threats (SWOT) survey as part of a landscape analysis of global enteric surveillance efforts. The current strengths of this network include excellent laboratory infrastructure, equipment and personnel that provide the opportunity for high-quality epidemiological studies and test platforms for point-of-care diagnostics. Weaknesses include inconsistent guidance and a splintered reporting system that hampers the comparison of data across regions or longitudinally. The newly chartered Enterics Surveillance Steering Committee (ESSC) is intended to provide clear mission guidance, a structured project review process, and central data management and analysis in support of rationally directed enteric disease surveillance efforts.
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http://dx.doi.org/10.1186/1471-2458-11-S2-S7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092417PMC
March 2011

The AFHSC-Division of GEIS Operations Predictive Surveillance Program: a multidisciplinary approach for the early detection and response to disease outbreaks.

BMC Public Health 2011 Mar 4;11 Suppl 2:S10. Epub 2011 Mar 4.

Armed Forces Health Surveillance Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.

The Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations (AFHSC-GEIS) initiated a coordinated, multidisciplinary program to link data sets and information derived from eco-climatic remote sensing activities, ecologic niche modeling, arthropod vector, animal disease-host/reservoir, and human disease surveillance for febrile illnesses, into a predictive surveillance program that generates advisories and alerts on emerging infectious disease outbreaks. The program's ultimate goal is pro-active public health practice through pre-event preparedness, prevention and control, and response decision-making and prioritization. This multidisciplinary program is rooted in over 10 years experience in predictive surveillance for Rift Valley fever outbreaks in Eastern Africa. The AFHSC-GEIS Rift Valley fever project is based on the identification and use of disease-emergence critical detection points as reliable signals for increased outbreak risk. The AFHSC-GEIS predictive surveillance program has formalized the Rift Valley fever project into a structured template for extending predictive surveillance capability to other Department of Defense (DoD)-priority vector- and water-borne, and zoonotic diseases and geographic areas. These include leishmaniasis, malaria, and Crimea-Congo and other viral hemorrhagic fevers in Central Asia and Africa, dengue fever in Asia and the Americas, Japanese encephalitis (JE) and chikungunya fever in Asia, and rickettsial and other tick-borne infections in the U.S., Africa and Asia.
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http://dx.doi.org/10.1186/1471-2458-11-S2-S10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092411PMC
March 2011

Department of Defense influenza and other respiratory disease surveillance during the 2009 pandemic.

BMC Public Health 2011 Mar 4;11 Suppl 2:S6. Epub 2011 Mar 4.

Armed Forces Health Surveillance Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.

The Armed Forces Health Surveillance Center's Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supports and oversees surveillance for emerging infectious diseases, including respiratory diseases, of importance to the U.S. Department of Defense (DoD). AFHSC-GEIS accomplishes this mission by providing funding and oversight to a global network of partners for respiratory disease surveillance. This report details the system's surveillance activities during 2009, with a focus on efforts in responding to the novel H1N1 Influenza A (A/H1N1) pandemic and contributions to global public health. Active surveillance networks established by AFHSC-GEIS partners resulted in the initial detection of novel A/H1N1 influenza in the U.S. and several other countries, and viruses isolated from these activities were used as seed strains for the 2009 pandemic influenza vaccine. Partners also provided diagnostic laboratory training and capacity building to host nations to assist with the novel A/H1N1 pandemic global response, adapted a Food and Drug Administration-approved assay for use on a ruggedized polymerase chain reaction platform for diagnosing novel A/H1N1 in remote settings, and provided estimates of seasonal vaccine effectiveness against novel A/H1N1 illness. Regular reporting of the system's worldwide surveillance findings to the global public health community enabled leaders to make informed decisions on disease mitigation measures and controls for the 2009 A/H1N1 influenza pandemic. AFHSC-GEIS's support of a global network contributes to DoD's force health protection, while supporting global public health.
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http://dx.doi.org/10.1186/1471-2458-11-S2-S6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092416PMC
March 2011