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  1. Article ; Online: Neuroinflammation in the Dorsal Root Ganglia and Dorsal Horn Contributes to Persistence of Nociceptor Sensitization in SIV-Infected Antiretroviral Therapy-Treated Macaques.

    Warfield, Rebecca / Robinson, Jake A / Podgorski, Rachel M / Miller, Andrew D / Burdo, Tricia H

    The American journal of pathology

    2023  Volume 193, Issue 12, Page(s) 2017–2030

    Abstract: Despite the development of antiretroviral therapy (ART), HIV-associated distal sensory polyneuropathy remains prevalent. Using SIV-infected rhesus macaques, this study examined molecular mechanisms of peripheral and central sensitization to infer chronic ...

    Abstract Despite the development of antiretroviral therapy (ART), HIV-associated distal sensory polyneuropathy remains prevalent. Using SIV-infected rhesus macaques, this study examined molecular mechanisms of peripheral and central sensitization to infer chronic pain from HIV infection. Previous studies identified atrophy in nociceptive neurons during SIV infection, which was associated with monocyte infiltration into the dorsal root ganglia (DRG). However, the sensory signaling mechanism connecting this pathology to symptoms remains unclear, especially because pain persists after resolution of high viremia and inflammation with ART. We hypothesized that residual DRG and dorsal horn neuroinflammation contributes to nociceptive sensitization. Using three cohorts of macaques [uninfected (SIV-), SIV-infected (SIV+), and SIV infected with ART (SIV+/ART)], this study showed an increase in the cellular and cytokine inflammatory profiles in the DRG of SIV+/ART macaques compared with uninfected animals. It found significant increase in the expression of nociceptive ion channels, TRPV1, and TRPA1 among DRG neurons in SIV+/ART compared with uninfected animals. SIV-infected and SIV+/ART animals showed reduced innervation of the nonpeptidergic nociceptors into the dorsal horn compared with uninfected animals. Finally, there were a significantly higher number of CD68
    MeSH term(s) Animals ; HIV Infections/pathology ; Simian Acquired Immunodeficiency Syndrome/complications ; Simian Acquired Immunodeficiency Syndrome/pathology ; Simian Immunodeficiency Virus/physiology ; Nociceptors/pathology ; Macaca mulatta ; Neuroinflammatory Diseases ; Ganglia, Spinal/pathology ; Atrophy/pathology
    Language English
    Publishing date 2023-09-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2023.08.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.76: Show issues Location:
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  2. Article ; Online: Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques.

    Podgorski, Rachel M / Robinson, Jake A / Smith, Mandy D / Mallick, Suvadip / Zhao, Huaqing / Veazey, Ronald S / Kolson, Dennis L / Bar, Katharine J / Burdo, Tricia H

    Retrovirology

    2023  Volume 20, Issue 1, Page(s) 13

    Abstract: A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to ... ...

    Abstract A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.
    MeSH term(s) Animals ; Humans ; Macaca mulatta ; Simian Acquired Immunodeficiency Syndrome/drug therapy ; HIV Infections/drug therapy ; Antiretroviral Therapy, Highly Active ; Simian Immunodeficiency Virus/genetics ; Brain ; HIV-1/genetics ; Virus Replication/physiology ; Viral Load
    Language English
    Publishing date 2023-08-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2142602-8
    ISSN 1742-4690 ; 1742-4690
    ISSN (online) 1742-4690
    ISSN 1742-4690
    DOI 10.1186/s12977-023-00628-5
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  3. Article ; Online: DNA analysis reveals non-falciparum malaria in the Democratic Republic of the Congo.

    Podgorski, Rachel M / Goff, Kelly A / Penney, Toni P / Maness, Nicholas J / Keating, Joseph / Yukich, Joshua O / Marx, Preston A

    Acta tropica

    2020  Volume 212, Page(s) 105557

    Abstract: Background: The World Health Organization (WHO) attributes the entirety of malaria infection and transmission in the Democratic Republic of the Congo (DRC) to Plasmodium falciparum, one of the several species of malaria known to infect humans. Recent ... ...

    Abstract Background: The World Health Organization (WHO) attributes the entirety of malaria infection and transmission in the Democratic Republic of the Congo (DRC) to Plasmodium falciparum, one of the several species of malaria known to infect humans. Recent studies have put forth some evidence that transmission of Plasmodium vivax may also be occurring in the DRC. As interventions and treatments differ between malaria species, it is crucial to maintain the most accurate understanding of malaria species diversity in each region.
    Methods: Blood samples were taken from aymptomatic children 0-5 years old living in three regions of the DRC in 2014. For this study, samples were taken from a larger pool of samples, collected as part of a population-based survey in three regions. Plasmodium infection was screened for using nested polymerase chain reaction (PCR) assays and species were confirmed by cloning and DNA sequencing.
    Results: Of 336 samples screened by PCR, 62.2% (n=209) initially tested positive for P. falciparum and 14.6% (n=49) initially tested positive for P. vivax. Sanger sequencing was performed on PCR-positive Plasmodium samples to confirm identity of Plasmodium species. Sequencing showed Plasmodium malariae in one blood sample and Plasmodium ovale in another sample. Plasmodium vivax was detected in 12/65 cases (18.5%). Overall, 14/65 sequenced cases (21.5%) were infected with a non-falciparum malaria. 330bp 18s P. vivax DNA sequences were obtained.
    Conclusions: This study reveals Plasmodium vivax and other non-falciparum malaria across several regions of the DRC, and enforces the importance of further testing and more precise diagnostics when testing for and treating malaria in the DRC. Here, we find a higher proportion of cases of P. vivax malaria than found in previous studies. This is the most robust DNA sequencing of Plasmodium vivax in the DRC to date.
    MeSH term(s) Child, Preschool ; DNA, Protozoan/analysis ; Democratic Republic of the Congo ; Humans ; Infant ; Infant, Newborn ; Malaria, Vivax/diagnosis ; Plasmodium falciparum/genetics ; Plasmodium vivax/genetics ; Polymerase Chain Reaction
    Chemical Substances DNA, Protozoan
    Language English
    Publishing date 2020-05-29
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 210415-5
    ISSN 1873-6254 ; 0001-706X
    ISSN (online) 1873-6254
    ISSN 0001-706X
    DOI 10.1016/j.actatropica.2020.105557
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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.136: Show issues Location:
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  4. Article: DNA analysis reveals non-falciparum malaria in the Democratic Republic of the Congo

    Podgorski, Rachel M / Goff, Kelly A / Penney, Toni P / Maness, Nicholas J / Keating, Joseph / Yukich, Joshua O / Marx, Preston A

    Acta tropica. 2020 Dec., v. 212

    2020  

    Abstract: The World Health Organization (WHO) attributes the entirety of malaria infection and transmission in the Democratic Republic of the Congo (DRC) to Plasmodium falciparum, one of the several species of malaria known to infect humans. Recent studies have ... ...

    Abstract The World Health Organization (WHO) attributes the entirety of malaria infection and transmission in the Democratic Republic of the Congo (DRC) to Plasmodium falciparum, one of the several species of malaria known to infect humans. Recent studies have put forth some evidence that transmission of Plasmodium vivax may also be occurring in the DRC. As interventions and treatments differ between malaria species, it is crucial to maintain the most accurate understanding of malaria species diversity in each region.Blood samples were taken from aymptomatic children 0-5 years old living in three regions of the DRC in 2014. For this study, samples were taken from a larger pool of samples, collected as part of a population-based survey in three regions. Plasmodium infection was screened for using nested polymerase chain reaction (PCR) assays and species were confirmed by cloning and DNA sequencing.Of 336 samples screened by PCR, 62.2% (n=209) initially tested positive for P. falciparum and 14.6% (n=49) initially tested positive for P. vivax. Sanger sequencing was performed on PCR-positive Plasmodium samples to confirm identity of Plasmodium species. Sequencing showed Plasmodium malariae in one blood sample and Plasmodium ovale in another sample. Plasmodium vivax was detected in 12/65 cases (18.5%). Overall, 14/65 sequenced cases (21.5%) were infected with a non-falciparum malaria. 330bp 18s P. vivax DNA sequences were obtained.This study reveals Plasmodium vivax and other non-falciparum malaria across several regions of the DRC, and enforces the importance of further testing and more precise diagnostics when testing for and treating malaria in the DRC. Here, we find a higher proportion of cases of P. vivax malaria than found in previous studies. This is the most robust DNA sequencing of Plasmodium vivax in the DRC to date.
    Keywords DNA ; Plasmodium falciparum ; Plasmodium malariae ; Plasmodium ovale ; Plasmodium vivax ; World Health Organization ; blood sampling ; diagnostic techniques ; malaria ; polymerase chain reaction ; species diversity ; surveys ; Democratic Republic of the Congo
    Language English
    Dates of publication 2020-12
    Publishing place Elsevier B.V.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 210415-5
    ISSN 1873-6254 ; 0001-706X
    ISSN (online) 1873-6254
    ISSN 0001-706X
    DOI 10.1016/j.actatropica.2020.105557
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    In stock of ZB MED Bonn / Germany

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  5. Article ; Online: Seroprevalence of anti-Lassa Virus IgG antibodies in three districts of Sierra Leone: A cross-sectional, population-based study.

    Grant, Donald S / Engel, Emily J / Roberts Yerkes, Nicole / Kanneh, Lansana / Koninga, James / Gbakie, Michael A / Alhasan, Foday / Kanneh, Franklyn B / Kanneh, Ibrahim Mustapha / Kamara, Fatima K / Momoh, Mambu / Yillah, Mohamed S / Foday, Momoh / Okoli, Adaora / Zeoli, Ashley / Weldon, Caroline / Bishop, Christopher M / Zheng, Crystal / Hartnett, Jessica /
    Chao, Karissa / Shore, Kayla / Melnik, Lilia I / Mucci, Mallory / Bond, Nell G / Doyle, Philip / Yenni, Rachael / Podgorski, Rachel / Ficenec, Samuel C / Moses, Lina / Shaffer, Jeffrey G / Garry, Robert F / Schieffelin, John S

    PLoS neglected tropical diseases

    2023  Volume 17, Issue 2, Page(s) e0010938

    Abstract: Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The ... ...

    Abstract Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown. This cross-sectional study aimed to establish a baseline point seroprevalence of IgG antibodies to LASV in three administrative districts of Sierra Leone and identify potential risk factors for seropositivity and LASV exposure.
    Methodology and principal findings: Between 2015 and 2018, over 10,642 participants from Kenema, Tonkolili, and Port Loko Districts were enrolled in this cross-sectional study. Previous LASV and LF epidemiological studies support classification of these districts as "endemic," "emerging," and "non-endemic", respectively. Dried blood spot samples were tested for LASV antibodies by ELISA to determine the seropositivity of participants, indicating previous exposure to LASV. Surveys were administered to each participant to assess demographic and environmental factors associated with a higher risk of exposure to LASV. Overall seroprevalence for antibodies to LASV was 16.0%. In Kenema, Port Loko, and Tonkolili Districts, seroprevalences were 20.1%, 14.1%, and 10.6%, respectively. In a multivariate analysis, individuals were more likely to be LASV seropositive if they were living in Kenema District, regardless of sex, age, or occupation. Environmental factors contributed to an increased risk of LASV exposure, including poor housing construction and proximity to bushland, forested areas, and refuse.
    Conclusions and significance: In this study we determine a baseline LASV seroprevalence in three districts which will inform future epidemiological, ecological, and clinical studies on LF and the LASV in Sierra Leone. The heterogeneity of the distribution of LASV and LF over both space, and time, can make the design of efficacy trials and intervention programs difficult. Having more studies on the prevalence of LASV and identifying potential hyper-endemic areas will greatly increase the awareness of LF and improve targeted control programs related to LASV.
    MeSH term(s) Animals ; Humans ; Sierra Leone/epidemiology ; Cross-Sectional Studies ; Seroepidemiologic Studies ; Lassa Fever/epidemiology ; Lassa virus ; Virus Diseases ; Murinae ; Antibodies, Viral ; Immunoglobulin G
    Chemical Substances Antibodies, Viral ; Immunoglobulin G
    Language English
    Publishing date 2023-02-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010938
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  6. Article ; Online: A medical records and data capture and management system for Lassa fever in Sierra Leone: Approach, implementation, and challenges.

    Shaffer, Jeffrey G / Schieffelin, John S / Gbakie, Michael / Alhasan, Foday / Roberts, Nicole B / Goba, Augustine / Randazzo, Jessica / Momoh, Mambu / Moon, Troy D / Kanneh, Lansana / Levy, Danielle C / Podgorski, Rachel M / Hartnett, Jessica N / Boisen, Matt L / Branco, Luis M / Samuels, Robert / Grant, Donald S / Garry, Robert F

    PloS one

    2019  Volume 14, Issue 3, Page(s) e0214284

    Abstract: Situated in southeastern Sierra Leone, Kenema Government Hospital (KGH) maintains one of the world's only Lassa fever isolation wards and was a strategic Ebola virus disease (EVD) treatment facility during the 2014 EVD outbreak. Since 2006, the Viral ... ...

    Abstract Situated in southeastern Sierra Leone, Kenema Government Hospital (KGH) maintains one of the world's only Lassa fever isolation wards and was a strategic Ebola virus disease (EVD) treatment facility during the 2014 EVD outbreak. Since 2006, the Viral Hemorrhagic Fever Consortium (VHFC) has carried out research activities at KGH, capturing clinical and laboratory data for suspected cases of Lassa fever. Here we describe the approach, progress, and challenges in designing and maintaining a data capture and management system (DCMS) at KGH to assist infectious disease researchers in building and sustaining DCMS in low-resource environments. Results on screening patterns and case-fatality rates are provided to illustrate the context and scope of the DCMS covered in this study. A medical records system and DCMS was designed and implemented between 2010 and 2016 linking historical and prospective Lassa fever data sources across KGH Lassa fever units and its peripheral health units. Data were captured using a case report form (CRF) system, enzyme-linked immunosorbent assay (ELISA) plate readers, polymerase chain reaction (PCR) machines, blood chemistry analyzers, and data auditing procedures. Between 2008 and 2016, blood samples for 4,229 suspected Lassa fever cases were screened at KGH, ranging from 219 samples in 2008 to a peak of 760 samples in 2011. Lassa fever case-fatality rates before and following the Ebola outbreak were 65.5% (148/226) and 89.5% (17/19), respectively, suggesting that fewer, but more seriously ill subjects with Lassa fever presented to KGH following the 2014 EVD outbreak (p = .040). DCMS challenges included weak specificity of the Lassa fever suspected case definition, limited capture of patient survival outcome data, internet costs, lapses in internet connectivity, low bandwidth, equipment and software maintenance, lack of computer teaching laboratories, and workload fluctuations due to variable screening activity. DCMS are the backbone of international research efforts and additional literature is needed on the topic for establishing benchmarks and driving goal-based approaches for its advancement in developing countries.
    MeSH term(s) Antibodies, Viral/blood ; Blood Chemical Analysis ; Databases, Factual ; Disease Outbreaks ; Hospitals, District ; Humans ; Information Dissemination ; Lassa Fever/diagnosis ; Lassa Fever/epidemiology ; Lassa Fever/mortality ; Lassa virus/genetics ; Lassa virus/immunology ; Lassa virus/isolation & purification ; Medical Records ; RNA, Viral/metabolism ; Sierra Leone/epidemiology ; Software ; Survival Rate
    Chemical Substances Antibodies, Viral ; RNA, Viral
    Language English
    Publishing date 2019-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0214284
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