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1.  Knowledge, attitudes and practices regarding rabies and exposure to bats in two rural communities in Guatemala 
BMC Research Notes  2015;8:955.
Background
Rabies is a fatal encephalitis caused by rabies virus, of the genus Lyssavirus. The principal reservoir for rabies in Latin America is the common vampire bat (Desmodus rotundus), which feeds routinely on the blood of cattle, and when livestock are scarce, may prey on other mammals, including humans. Although rabies is endemic in common vampire bat populations in Guatemala, there is limited research on the extent of exposure to bats among human populations living near bat refuges.
Results
A random sample of 270 of 473 households (57%) in two communities located within 2 Km of a known bat roost was selected and one adult from each household was interviewed. Exposure to bats (bites, scratches or bare skin contact) was reported by 96 (6%) of the 1,721 residents among the selected households. Of those exposed, 40% received rabies post-exposure prophylaxis. Four percent of household respondents reported that they would seek rabies post exposure prophylaxis if they were bitten by a bat.
Conclusions
These findings demonstrate that exposure to bats in communities near bat roosts is common but recognition of the potential for rabies transmission from bats is low. There is a need for educational outreach to raise awareness of bat-associated rabies, prevent exposures to bats and ensure appropriate health-seeking behaviours for bat-inflicted wounds, particularly among communities living near bat roosts in Guatemala.
doi:10.1186/s13104-014-0955-1
PMCID: PMC4302579  PMID: 25576098
Rabies; Bat bite; Health practices; Post-exposure prophylaxis; Guatemala; Rabies prevention; Vampire bat
2.  Child Exposure to Parental Violence and Psychological Distress Associated With Delayed Milestones 
Pediatrics  2013;132(6):e1577-e1583.
OBJECTIVE:
To examine the association between parental report of intimate partner violence (IPV) and parental psychological distress (PPD) with child attainment of developmental milestones.
METHODS:
By using data collected from a large cohort of primary care patients, this cross-sectional study examined the relationship between parental report of IPV and/or PPD and the attainment of developmental milestones within the first 72 months of a child’s life. Multivariate logistic regression analyses were used to adjust for parental report of child abuse concern and sociodemographic characteristics.
RESULTS:
Our study population included 16 595 subjects. Children of parents reporting both IPV and PPD (n = 88; 0.5%) were more likely to fail at least 1 milestone across the following developmental domains: language (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3–3.3), personal-social (aOR 1.9; 95% CI 1.2–2.9), and gross motor (aOR 3.0; 95% CI 1.8–5.0). Significant associations for those reporting IPV-only (n = 331; 2.0%) were found for language (aOR 1.4; 95% CI 1.1–1.9), personal-social (aOR 1.7; 95% CI 1.4–2.2), and fine motor-adaptive (aOR 1.7; 95% CI 1.0–2.7). Significant associations for those reporting PPD-only (n = 1920; 11.6%) were found for: language (aOR 1.5; 95% CI 1.3–1.7), personal-social (aOR 1.6; 95% CI 1.5–1.8), gross motor (aOR 1.6; 95% CI 1.4–1.8), and fine-motor adaptive (aOR 1.6; 95% CI 1.3–2.0).
CONCLUSIONS:
Screening children for IPV and PPD helps identify those at risk for poor developmental outcomes who may benefit from early intervention.
doi:10.1542/peds.2013-1020
PMCID: PMC3838530  PMID: 24190682
child development; computerized clinical decision support; developmental milestones; intimate partner violence; parental psychological distress
3.  Right Place, Wrong Species: A 20-Year Review of Rabies Virus Cross Species Transmission among Terrestrial Mammals in the United States 
PLoS ONE  2014;9(10):e107539.
Introduction
In the continental US, four terrestrial mammalian species are reservoirs for seven antigenic rabies virus variants. Cross species transmission (CST) occurs when a rabies virus variant causes disease in non-reservoir species.
Methods
This study analyzed national surveillance data for rabies in terrestrial mammals. The CST rate was defined as: number of rabid non-reservoir animals/number of rabid reservoir animals. CST rates were analyzed for trend. Clusters of high CST rate counties were evaluated using space-time scanning statistics.
Results
The number of counties reporting a raccoon variant CST rate >1.0 increased from 75 in 1992 to 187 in 2011; counties with skunk variant CST rates >1.0 remained unchanged during the same period. As of 2011, for every rabid raccoon reported within the raccoon variant region, there were 0.73 cases of this variant reported in non-reservoir animals. Skunks were the most common non-reservoir animal reported with the raccoon rabies variant. Domestic animals were the most common non-reservoir animal diagnosed with a skunk rabies virus variant (n = 1,601). Cross species transmission rates increased fastest among domestic animals.
Conclusions
Cross species transmission of rabies virus variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control. Cross species transmission in raccoon rabies enzootic regions increased dramatically during the study period. Pet owners should vaccinate their dogs and cats to ensure against CST, particularly in regions with active foci of rabies circulation. Clusters of high CST activity represent areas for further study to better understand interspecies disease transmission dynamics. Each CST event has the potential to result in a rabies virus adapted for sustained transmission in a new species; therefore further understanding of the dynamics of CST may help in early detection or prevention of the emergence of new terrestrial rabies virus variants.
doi:10.1371/journal.pone.0107539
PMCID: PMC4189788  PMID: 25295750
4.  Bat Rabies in Guatemala 
Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. As part of a larger pathogen detection program, enhanced bat rabies surveillance was conducted in Guatemala, between 2009 and 2011. A total of 672 bats of 31 species were sampled and tested for rabies. The prevalence of rabies virus (RABV) detection among all collected bats was low (0.3%). Viral antigens were detected and infectious virus was isolated from the brains of two common vampire bats (Desmodus rotundus). RABV was also isolated from oral swabs, lungs and kidneys of both bats, whereas viral RNA was detected in all of the tissues examined by hemi-nested RT-PCR except for the liver of one bat. Sequencing of the nucleoprotein gene showed that both viruses were 100% identical, whereas sequencing of the glycoprotein gene revealed one non-synonymous substitution (302T,S). The two vampire bat RABV isolates in this study were phylogenetically related to viruses associated with vampire bats in the eastern states of Mexico and El Salvador. Additionally, 7% of sera collected from 398 bats demonstrated RABV neutralizing antibody. The proportion of seropositive bats varied significantly across trophic guilds, suggestive of complex intraspecific compartmentalization of RABV perpetuation.
Author Summary
In this study we provide results of the first active and extensive surveillance effort for rabies virus (RABV) circulation among bats in Guatemala. The survey included multiple geographic areas and multiple species of bats, to assess the broader public and veterinary health risks associated with rabies in bats in Guatemala. RABV was isolated from vampire bats (Desmodus rotundus) collected in two different locations in Guatemala. Sequencing of the isolates revealed a closer relationship to Mexican and Central American vampire bat isolates than to South American isolates. The detection of RABV neutralizing antibodies in 11 species, including insectivorous, frugivorous, and sanguivorous bats, demonstrates viral circulation in both hematophagous and non-hematophagous bat species in Guatemala. The presence of bat RABV in rural communities requires new strategies for public health education regarding contact with bats, improved laboratory-based surveillance of animals associated with human exposures, and novel techniques for modern rabies prevention and control. Additionally, healthcare practitioners should emphasize the collection of a detailed medical history, including questions regarding bat exposure, for patients presenting with clinical syndromes compatible with rabies or any clinically diagnosed progressive encephalitis.
doi:10.1371/journal.pntd.0003070
PMCID: PMC4117473  PMID: 25080103
5.  A tool kit for rapid cloning and expression of recombinant antibodies 
Scientific Reports  2014;4:5885.
Over the last four decades, molecular cloning has evolved tremendously. Efficient products allowing assembly of multiple DNA fragments have become available. However, cost-effective tools for engineering antibodies of different specificities, isotypes and species are still needed for many research and clinical applications in academia. Here, we report a method for one-step assembly of antibody heavy- and light-chain DNAs into a single mammalian expression vector, starting from DNAs encoding the desired variable and constant regions, which allows antibodies of different isotypes and specificity to be rapidly generated. As a proof of principle we have cloned, expressed and characterized functional recombinant tumor-associated antigen-specific chimeric IgE/κ and IgG1/κ, as well as recombinant grass pollen allergen Phl p 7 specific fully human IgE/λ and IgG4/λ antibodies. This method utilizing the antibody expression vectors, available at Addgene, has many applications, including the potential to support simultaneous processing of antibody panels, to facilitate mechanistic studies of antigen-antibody interactions and to conduct early evaluations of antibody functions.
doi:10.1038/srep05885
PMCID: PMC4115235  PMID: 25073855
6.  Associations between early exposure to intimate partner violence, parental depression and subsequent mental health outcomes 
JAMA pediatrics  2013;167(4):341-347.
Objective
To examine the association between parent reports of intimate partner violence (IPV) and depressive symptoms within the first 3 years of a child’s life with subsequent mental health conditions and psychotropic drug treatment.
Design
Prospective cohort study linking parental IPV and depression with subsequent billing and pharmacy data.
Setting
4 pediatric clinics between November 2004 and June 2012
Patients/Participants
2,422 children
Main Exposure
Any report of IPV and/or parental depressive symptoms from birth to 3 years of age.
Main Outcome Measures
ICD-9 mental health diagnoses and any psychotropic drug treatment between 3 and 6 years of age.
Results
2.4% of caregivers (n=58) reported both IPV and depressive symptoms before their children were 3 years of age, 3% (n=69) of caregivers reported IPV only, 29% (n=704) reported depressive symptoms only, and 65.7% (n=1,591) reported neither exposure. Children of parents reporting both IPV and depressive symptoms were more likely to have a diagnosis of attention-deficit hyperactivity disorder (ADHD) (AOR 4.0; 95% CI: 1.5–10.9), even after adjusting for child gender, race/ethnicity, and insurance type. Children whose parents reported depressive symptoms were more likely to have been prescribed psychotropic medication (AOR 1.9; 95% CI: 1.0–3.4).
Conclusions
Exposure to both IPV and depression before 3 years is associated with preschool-onset ADHD; and early exposure to parental depression is associated with being prescribed psychotropic medication.
doi:10.1001/jamapediatrics.2013.780
PMCID: PMC4029325  PMID: 23381234
Mental Health; Family Violence; Depression; Primary Healthcare; Decision Support Systems; Clinical; ADHD
7.  A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special? 
Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.
doi:10.1098/rspb.2012.2753
PMCID: PMC3574368  PMID: 23378666
trait-based approaches; zoonoses; viral richness; reservoir host; spillover; Chiroptera
8.  New World Bats Harbor Diverse Influenza A Viruses 
PLoS Pathogens  2013;9(10):e1003657.
Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.
Author Summary
Previous studies indicated that a novel influenza A virus (H17N10) was circulating in fruit bats from Guatemala (Central America). Herein, we investigated whether similar viruses are present in bat species from South America. Analysis of rectal swabs from bats sampled in the Amazon rainforest region of Peru identified another new influenza A virus from bats that is phylogenetically distinct from the one identified in Guatemala. The genes that encode the surface proteins of the new virus from the flat-faced fruit bat were designated as new subtype H18N11. Serologic testing of blood samples from several species of Peruvian bats indicated a high prevalence of antibodies to the surface proteins. Phylogenetic analyses demonstrate that bat populations from Central and South America maintain as much influenza virus genetic diversity in some gene segments as all other mammalian and avian species combined. The crystal structures of the hemagglutinin and neuraminidase proteins indicate that sialic acid is not a receptor for virus attachment nor a substrate for release, suggesting a novel mechanism of influenza A virus attachment and activation of membrane fusion for entry into host cells. In summary, our findings indicate that bats constitute a potentially important reservoir for influenza viruses.
doi:10.1371/journal.ppat.1003657
PMCID: PMC3794996  PMID: 24130481
9.  Prevalence and Diversity of Bartonella spp. in Bats in Peru 
Bartonella infections were investigated in bats in the Amazon part of Peru. A total of 112 bats belonging to 19 species were surveyed. Bartonella bacteria were cultured from 24.1% of the bats (27/112). Infection rates ranged from 0% to 100% per bat species. Phylogenetic analyses of gltA of the Bartonella isolates revealed 21 genetic variants clustering into 13 divergent phylogroups. Some Bartonella strains were shared by bats of multiple species, and bats of some species were infected with multiple Bartonella strains, showing no evident specific Bartonella sp.–bat relationships. Rarely found in other bat species, the Bartonella strains of phylogroups I and III discovered from the common vampire bats (Desmodus rotundus) were more specific to the host bat species, suggesting some level of host specificity.
doi:10.4269/ajtmh.2012.12-0097
PMCID: PMC3435358  PMID: 22826480
10.  IgG4 antibodies and cancer-associated inflammation 
Oncoimmunology  2013;2(7):e24889.
The role of B cells and antibodies in cancer is insufficiently understood but is receiving increasing attention. We have recently identified IgG4 as an antibody subclass elicited by melanoma-associated interleukin-10-driven inflammation. In this setting, IgG4 exhibit inefficient immunostimulatory capacity and block the cytotoxic activities of other antibodies. These previously unappreciated mechanisms of immune escape may constitute promising targets for the development of novel anticancer immunotherapies.
doi:10.4161/onci.24889
PMCID: PMC3782134  PMID: 24073371
B cells; FcγRI; IL-10; IgG4; VEGF; antibody effector functions; cancer inflammation; immune escape; melanoma
11.  IgG4 subclass antibodies impair antitumor immunity in melanoma 
The Journal of Clinical Investigation  2013;123(4):1457-1474.
Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches.
doi:10.1172/JCI65579
PMCID: PMC3613918  PMID: 23454746
12.  Evidence of Rabies Virus Exposure among Humans in the Peruvian Amazon 
In May of 2010, two communities (Truenococha and Santa Marta) reported to be at risk of vampire bat depredation were surveyed in the Province Datem del Marañón in the Loreto Department of Perú. Risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. Rabies virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG) antibodies were detected in the sera of three individuals, two of whom were also seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent with positive rVNA results reported prior vaccination and 86% (six of seven) of rVNA-positive respondents reported being bitten by bats, these data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.
doi:10.4269/ajtmh.2012.11-0689
PMCID: PMC3414554  PMID: 22855749
13.  Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies 
PLoS ONE  2011;6(4):e19330.
Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.
doi:10.1371/journal.pone.0019330
PMCID: PMC3084832  PMID: 21559411
14.  Antimicrobial Activities of Amine- and Guanidine-Functionalized Cholic Acid Derivatives 
Compounds in a series of cholic acid derivatives, designed to mimic the activities of polymyxin B and its derivatives, act as both potent antibiotics and effective permeabilizers of the outer membranes of gram-negative bacteria. Some of these compounds rival polymyxin B in antibacterial activity against gram-negative bacteria and are also very active against gram-positive organisms. Other compounds interact synergistically with hydrophobic antibiotics to inhibit bacterial growth.
PMCID: PMC89276  PMID: 10348750

Results 1-14 (14)