DoD-GEIS Rift Valley Fever Monitoring and Prediction System as a Tool for Defense and US Diplomacy

Over the last 10 years the Armed Forces Health Surveillance Center's Global Emerging Infections Surveillance and Response System (GEIS) partnering with NASA'S Goddard Space Flight Center and USDA's USDA-Center for Medical, Agricultural & Veterinary Entomology established and have operated the Rift Valley fever Monitoring and Prediction System to monitor, predict and assess the risk of Rift Valley fever outbreaks and other vector-borne diseases over Africa and the Middle East. This system is built on legacy DoD basic research conducted by Walter Reed Army Institute of Research overseas laboratory (US Army Medical Research Unit-Kenya) and the operational satellite environmental monitoring by NASA GSFC. Over the last 10 years of operation the system has predicted outbreaks of Rift Valley fever in the Horn of Africa, Sudan, South Africa and Mauritania. The ability to predict an outbreak several months before it occurs provides early warning to protect deployed forces, enhance public health in concerned countries and is a valuable tool use.d by the State Department in US Diplomacy. At the international level the system has been used by the Food and Agricultural Organization (FAD) and the World Health Organization (WHO) to support their monitoring, surveillance and response programs in the livestock sector and human health. This project is a successful testament of leveraging resources of different federal agencies to achieve objectives of force health protection, health and diplomacy

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

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

Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments

Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naiveté to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature, emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non-Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Mutations in the Human UBR1 Gene and the Associated Phenotypic Spectrum

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n=29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. the review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. for all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.German Research FoundationUniv Hosp Magdeburg, Inst Human Genet, D-39120 Magdeburg, GermanyUniv Hosp Erlangen, Inst Human Genet, Erlangen, GermanyHosp Nacl Ninos Dr Carlos Saenz Herrera, Dept Med, San Jose, Costa RicaKlinikum Bremen Mitte, Bremen, GermanyCHU Vaudois, Dept Med Genet, CH-1011 Lausanne, SwitzerlandUniv Hosp, Dept Pediat Surg, Poitiers, FranceHosp La Fe, Dept Pediat, E-46009 Valencia, SpainAMC Univ Hosp, Dept Pediat Genet, Amsterdam, NetherlandsVanderbilt Univ, Monroe Carell Jr Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Nashville, TN 37235 USACleveland Clin, Genom Med Inst, Cleveland, OH 44106 USAGuys Hosp, London SE1 9RT, EnglandKariminejad Najmabadi Pathol & Genet Ctr, Tehran, IranGreenwood Genet Ctr, Greenwood, SC 29646 USAUmea Univ, Dept Med Biosci Med & Clin Genet, Umea, SwedenWomens & Childrens Hosp, SA Clin Genet Serv, Adelaide, SA, AustraliaStiftung Deutsch Klin Diagnost GmbH, Fachbereich Kinder & Jugendmed, Wiesbaden, GermanyUniv São Paulo, Dept Pediat, São Paulo, BrazilUniv British Columbia, Dept Pediat, Div Biochem Dis, BC Childrens Hosp, Vancouver, BC V6T 1W5, CanadaCtr Human Genet, Ingelheim, GermanyNanjing Med Univ, Nanjing Childrens Hosp, Dept Digest Dis, Nanjing, Jiangsu, Peoples R ChinaUniv Klinikum Bonn, Zentrum Kinderheilkunde, Bonn, GermanyUniv Tehran Med Sci, Childrens Med Ctr, Res Ctr Immunodeficiencies, Tehran, IranUniv Tehran Med Sci, Dept Immunol, Tehran, IranKing Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi ArabiaOndokuz Mayis Univ, Dept Med, Samsun, TurkeyOndokuz Mayis Univ, Dept Pediat Genet, Samsun, TurkeyAl Thawra Teaching Hosp, Dept Pediat, Sanaa, YemenHosp Gen Mexico City, Fac Med, Dept Human Genet, Mexico City, DF, MexicoUniv Med Ctr Utrecht, Dept Med Genet, Utrecht, NetherlandsNatl Childrens Hosp, San Jose, Costa RicaSisli Etfal Res Hosp, Dept Med Genet, Istanbul, TurkeyNizams Inst Med Sci, Dept Med Genet, Hyderabad, Andhra Pradesh, IndiaMaulana Azad Med Coll, Dept Pediat, New Delhi, IndiaDeenanath Mangeshkar Hosp & Res Ctr, Dept Genet, Erandawane, IndiaMinist Hlth, Dept Pediat, Manama, BahrainUniv Fed Bahia, Fac Med, Hosp Univ Prof Edgar Santos, Pediat Endocrinol Unit, Salvador, BA, BrazilErnst Moritz Arndt Univ Greifswald, Univ Med, Dept Med A, Greifswald, GermanyTech Univ Munich, Else Kroner Fresenius Zentrum Ernahrungsmed, Freising Weihenstephan, GermanyTech Univ Munich, Zent Inst Ernahrungs & Lebensmittelforsch, Freising Weihenstephan, GermanyTech Univ Munich, Klinikum Rechts Isar, Dept Pediat, D-80290 Munich, GermanyGerman Research Foundation: DFG ZE 524/2-3Web of Scienc