348 research outputs found
HIV Infection and Ocular Disease in South Africa
The burden of ocular disease in sub-Saharan African countries is disproportionally high, especially among HIV-infected individuals. This thesis presents the results of studies that provide novel insight into the clinical field of ophthalmology in a high HIV prevalence setting in rural South Africa (Mopani District, Limpopo Province). This insight opens the door for further improvement of the clinical care for individuals affected by HIV-associated ocular diseases
High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa
Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa
Early- and late-stage ocular complications of herpes zoster ophthalmicus in rural South Africa
OBJECTIVES : To describe the spectrum of ocular complications of herpes zoster ophthalmicus (HZO)
in rural South Africa.
METHODS : Patients presenting with visual complaints and active or healed HZO at the
ophthalmology outpatient department of three hospitals in rural South Africa were included in this
study. Demographic and clinical data were collected, and HIV status was determined for all
participants.
RESULTS : Forty-eight patients were included, and 81% were HIV infected. Poor vision was reported
by 94% of patients, painful eye by 79% and photophobia by 63%. A diverse spectrum of ocular
complications was observed with corneal inflammation and opacification in 77% followed by
anterior uveitis in 65%. The majority (65%) presented with late-stage ocular complications
associated with irreversible loss of vision whereas early-stage complications, such as punctate
epithelial keratitis and anterior uveitis, were less common. Blindness of the affected eye was observed
in 68% of patients with late-stage complications. There was a considerable delay between onset of
symptoms and first presentation to the ophthalmology outpatient department (median time 35 days;
range 1–2500 days), and longer delay was associated with late-stage ocular complications (P = 0.02).
CONCLUSIONS : HZO patients present with relatively late-stage ocular complications, and blindness
among these patients is common. The delayed presentation to the ophthalmology outpatient
department of hospitals in our rural setting is of concern, and efforts to improve ocular outcomes of
HZO are urgently needed.In part funded by the Rotterdamse Stichting Blindenbelangen
and the Rotterdam Global Health Initiative. Anova
Health Institute receives a grant from the US President’s
Emergency Plan for AIDS Relief (PEPFAR) programme
via the US Agency for International Development.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-31562017-03-31hb2016Medical Microbiolog
A novel antigen capture ELISA for the specific detection of IgG antibodies to elephant endotheliotropic herpes virus
BACKGROUND
Elephants are classified as critically endangered animals by the International Union for Conservation of Species (IUCN). Elephant endotheliotropic herpesvirus (EEHV) poses a large threat to breeding programs of captive Asian elephants by causing fatal haemorrhagic disease. EEHV infection is detected by PCR in samples from both clinically ill and asymptomatic elephants with an active infection, whereas latent carriers can be distinguished exclusively via serological assays. To date, identification of latent carriers has been challenging, since there are no serological assays capable of detecting seropositive elephants.
RESULTS
Here we describe a novel ELISA that specifically detects EEHV antibodies circulating in Asian elephant plasma/serum. Approximately 80 % of PCR positive elephants display EEHV-specific antibodies. Monitoring three Asian elephant herds from European zoos revealed that the serostatus of elephants within a herd varied from non-detectable to high titers. The antibody titers showed typical herpes-like rise-and-fall patterns in time which occur in all seropositive animals in the herd more or less simultaneously.
CONCLUSIONS
This study shows that the developed ELISA is suitable to detect antibodies specific to EEHV. It allows study of EEHV seroprevalence in Asian elephants. Results confirm that EEHV prevalence among Asian elephants (whether captive-born or wild-caught) is high
Triazole Fungicides Can Induce Cross-Resistance to Medical Triazoles in Aspergillus fumigatus
Contains fulltext :
103858.pdf (publisher's version ) (Open Access)BACKGROUND: Azoles play an important role in the management of Aspergillus diseases. Azole resistance is an emerging global problem in Aspergillus fumigatus, and may develop through patient therapy. In addition, an environmental route of resistance development has been suggested through exposure to 14alpha-demethylase inhibitors (DMIs). The main resistance mechanism associated with this putative fungicide-driven route is a combination of alterations in the Cyp51A-gene (TR(34)/L98H). We investigated if TR(34)/L98H could have developed through exposure to DMIs. METHODS AND FINDINGS: Thirty-one compounds that have been authorized for use as fungicides, herbicides, herbicide safeners and plant growth regulators in The Netherlands between 1970 and 2005, were investigated for cross-resistance to medical triazoles. Furthermore, CYP51-protein homology modeling and molecule alignment studies were performed to identify similarity in molecule structure and docking modes. Five triazole DMIs, propiconazole, bromuconazole, tebuconazole, epoxiconazole and difenoconazole, showed very similar molecule structures to the medical triazoles and adopted similar poses while docking the protein. These DMIs also showed the greatest cross-resistance and, importantly, were authorized for use between 1990 and 1996, directly preceding the recovery of the first clinical TR(34)/L98H isolate in 1998. Through microsatellite genotyping of TR(34)/L98H isolates we were able to calculate that the first isolate would have arisen in 1997, confirming the results of the abovementioned experiments. Finally, we performed induction experiments to investigate if TR(34)/L98H could be induced under laboratory conditions. One isolate evolved from two copies of the tandem repeat to three, indicating that fungicide pressure can indeed result in these genomic changes. CONCLUSIONS: Our findings support a fungicide-driven route of TR(34)/L98H development in A. fumigatus. Similar molecule structure characteristics of five triazole DMIs and the three medical triazoles appear the underlying mechanism of cross resistance development. Our findings have major implications for the assessment of health risks associated with the use of triazole DMIs
Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa
The purpose of this investigation was to determine
the clinical and corneal microbial profile of infectious keratitis
in a high human immunodeficiency virus (HIV) prevalence
setting in rural South Africa. Data in this cross-sectional study
were collected from patients presenting with symptoms of
infectious keratitis (n = 46) at the ophthalmology outpatient
department of three hospitals in rural South Africa. Corneal
swabs were tested for herpes simplex virus type 1 (HSV-1)
and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus
DNA by real-time polymerase chain reaction (PCR) and for
bacteria and fungi by culture. Based on clinical history, disease
characteristics and laboratory results, 29 (63 %) patients
were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and
17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was
detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively.
Among clinically defined viral keratitis cases, a negative
viral swab was predominantly (93 %) observed in cases with
subepithelial inflammation and was significantly associated
with an increased duration of symptoms (p=0.003). The majority
of bacteria cultured were Gram-positive (24/35), including
Staphylococcus epidermidis and S. aureus. Viral aetiology
was significantly associated with a history of herpes zoster
ophthalmicus (p < 0.001) and a trend was observed between
viral aetiology and HIV infection (p = 0.06). Twenty-one
(47 %) keratitis cases were complicated by anterior uveitis,
of which 18 (86 %) were HIV-infected cases with viral keratitis.
The data implicate a high prevalence of herpetic keratitis,
in part complicated by bacterial superinfection and/or uveitis,
in HIV-infected individuals presenting with infectious keratitis
in rural South Africa.http://link.springer.com/journal/10096hb2016Medical Microbiolog
Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice
Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425. We show that LPA1/3 inhibition significantly impaired atherosclerosis progression. Treatment with Ki16425 also resulted in reduced CCL2 production and secretion, which led to less monocyte and neutrophil infiltration. Furthermore, we provide evidence that LPA1/3 blockade enhanced the percentage of non-inflammatory, Ly6Clow monocytes and CD4+ CD25+ FoxP3+ T-regulatory cells. Finally, we demonstrate that LPA1/3 antagonism mildly reduced plasma LDL cholesterol levels. Therefore, pharmacological inhibition of LPA1/3 receptors may prove a promising approach to diminish atherosclerosis development.Biopharmaceutic
EEHV1A glycoprotein B subunit vaccine elicits humoral and cell-mediated immune responses in mice
DATA AVAILABILITY : Data will be made available on request.Asian elephants are an endangered species facing many threats, including severe hemorrhagic disease
(HD) caused by the elephant endotheliotropic herpesvirus (EEHV). EEHV-HD is the leading cause of death
in captive juvenile Asian elephants in North America and Europe, and also affects elephants in their natural
range countries. Significant challenges exist for successful treatment of EEHV-HD, which include
timely recognition of disease onset and limited availability of highly effective treatment options. To
address this problem, our goal is to prevent lethal disease in young elephants by developing a vaccine
that elicits robust and durable humoral and cell-mediated immunity against EEHV. EEHV glycoprotein
B (gB) is a major target for cellular and humoral immunity in elephants previously exposed to EEHV.
Therefore, we generated a vaccine containing recombinant EEHV1A gB together with a liposome formulated
TLR-4 and saponin combination adjuvant (SLA-LSQ). CD-1 mice that received one or two vaccinations
with the vaccine elicited significant anti-gB antibody and polyfunctional CD4+ and CD8+ T cell
responses, while no adverse effects of vaccination were observed. Overall, our findings demonstrate that
an adjuvanted gB protein subunit vaccine stimulates robust humoral and cell-mediated immune
responses and supports its potential use in elephants.The Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the CPRIT Core Facility Support Award, the NIH, the International Elephant Foundation (IEF) and Houston Zoo and funds acquired via Named Fund Friends of VetMed to the Utrecht University EEHV research group.http://www.elsevier.com/locate/vaccineam2023Veterinary Tropical Disease
Apolipoprotein A1 deficiency in mice primes bone marrow stem cells for T cell lymphopoiesis
The bone marrow has emerged as a potentially important target in cardiovascular disease as it generates all leukocytes involved in atherogenesis. In the current study, we evaluated whether a change in bone marrow functionality underlies the increased atherosclerosis susceptibility associated with high-density lipoprotein (HDL) deficiency. We found that HDL deficiency in mice due to the genetic lack of hepatocyte-derived apolipoprotein A1 (APOA1) was associated with an increase in the Lin-Sca-1+Kit+ (LSK) bone marrow stem cell population and lymphoid-primed multipotent progenitor numbers, which translated into a higher production and systemic flux of T cell subsets. In accordance with APOA1 deficiency-associated priming of stem cells to increase T lymphocyte production, atherogenic diet-fed low-density lipoprotein receptor knockout mice transplanted with bone marrow from APOA1-knockout mice displayed marked lymphocytosis as compared to wild-type bone marrow recipients. However, atherosclerotic lesion sizes and collagen contents were similar in the two groups of bone marrow recipients. In conclusion, systemic lack of APOA1 primes bone marrow stem cells for T cell lymphopoiesis. Our data provide novel evidence for a regulatory role of HDL in bone marrow functioning in normolipidemic mice.Biopharmaceutic
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