8 research outputs found
CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide
BACKGROUND : Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play
a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of
these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and
increased microbial translocation (MT).
METHODS : Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS
patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory
bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections
(OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of
proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension
Array System. Statistical analyses were performed using Spearman’s correlation and Wilcoxon matched-pair tests.
Results between groups were analyzed using the Kruskal-Wallis with Dunn’s post-test and the Mann–Whitney U tests.
RESULTS : None of the study participants had evidence of enteric co-infections as assessed by stool analysis and
histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased
infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor
(TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C)
motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC
revealed significant co-localization of TNF-α and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked
increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide
(LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated
mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS
CONCLUSIONS : Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistentinflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatmentstrategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoringthe epithelial barrier and limiting MT in HIV-infected patients.This research and selected researchers (EC, TR, PM, SM and CS) were funded
in part by a grant from the Delegation of the European Union to South
Africa: “Drug Resistance Surveillance and Treatment Monitoring Network for
the Public Sector HIV Antiretroviral Treatment Programme in the Free State –
Sante 2007/147-790” and by a grant from the National Research Council of
South Africa, Unlocking the Future 61509.http://www.biomedcentral.com/bmcinfectdisam201
A retrospective 5-year review of rubella in South Africa prior to the introduction of a rubella-containing vaccine
South Africa has yet to introduce a rubella-containing vaccine (RCV) into its Expanded Programme on Immunisation (EPI). Here we evaluated the incidence of laboratory-confirmed
rubella and congenital rubella syndrome (CRS) cases over the years 2015 to 2019, to document the epidemiology of rubella and CRS within South Africa prior to a RCV introduction. This
retrospective study evaluated the number of laboratory-confirmed rubella cases reported
through the national febrile rash surveillance system. A positive test for rubella immunoglobulin
M (IgM) antibodies was considered a confirmed rubella case. For CRS cases, we reported laboratory-confirmed CRS cases collected from 28 sentinel-sites from all nine provinces of South
Africa. From 2015–2019, 19 773 serum samples were tested for rubella IgM antibodies, 6 643
(33.6%) were confirmed rubella cases. Rubella was seasonal, with peaks in spring (September to November). Case numbers were similar between males (n = 3 239; 50.1%) and females
(n = 3 232; 49.9%). The highest burden of cases occurred in 2017 (n = 2 526; 38%). The
median age was 5 years (IQR: 3–7 years). Importantly, of females with rubella, 5.0% (161 of 3
232) of the cases were among women of reproductive age (15–44 years). A total of 62 CRS
cases were reported, the mortality rate was 12.9% (n = 8), and the most common birth defect
was congenital heart disease. In conclusion, rubella is endemic in South Africa. Children
below the age of 10 years were the most affected, however, rubella was also reported among
women of reproductive age. The baseline data represented here provides insight into the burden of rubella and CRS in South Africa prior to the introduction of a RCV, and can enable planning of RCV introduction into the South African EPI.The National Institute for Communicable Diseases, a division of the National Health Laboratory Service, South Africa.http://www.plosone.orgdm2022School of Health Systems and Public Health (SHSPH
Persistent microbial translocation and immune activation in HIV-1–infected South Africans receiving combination antiretroviral therapy
BACKROUND: Microbial translocation contributes to immune activation and disease progression during chronic
human immunodeficiency virus type 1 (HIV-1) infection. However, its role in the African AIDS epidemic remains
controversial. Here, we investigated the relationship between markers of monocyte activation, plasma lipopolysaccharide
(LPS), and HIV-1 RNA in South Africans prioritized to receive combination antiretroviral therapy
(cART).
METHODS: Ten HIV-1–negative African controls and 80 HIV-1–infected patients with CD4 T cell counts !200
cells/mL were sampled prior to ( ) or np60 during (np20) receipt of effective cART. Viral load was measured
by Nuclisens; LPS by the Limulus amoebocyte lysate assay; monocyte and T cell subsets by flow cytometry; and
soluble CD14, cytokines, and chemokines by enzyme-linked immunosorbent assay and customized Bio-Plex plates.
RESULTS: Three distinct sets of markers were identified. CCL2, CXCL10, and CD14+CD16+ monocyte levels
were positively correlated with HIV-1 viremia. This finding, together with cART-induced normalization of these
markers, suggests that their upregulation was driven by HIV-1. Plasma interleukin-6 was associated with the
presence of opportunistic coinfections. Soluble CD14 and tumor necrosis factor were linked to plasma LPS levels
and, as observed for LPS, remained elevated in patients receiving effective cART.
CONCLUSIONS: Microbial translocation is a major force driving chronic inflammation in HIV-infected Africans
receiving cART. Prevention of monocyte activation may be especially effective at enhancing therapeutic outcomes
The performance of hepatitis C virus (HCV) antibody point-of-care tests on oral fluid or whole blood and dried blood spot testing for HCV serology and viral load among individuals at higher risk for HCV in South Africa
Background and Aims: To enhance screening and diagnosis in those at-risk of hepatitis
C virus (HCV), efficient and improved sampling and testing is required. We investigated
the performance of point-of-care (POC) tests and dried blood spots (DBS) for
HCV antibody and HCV RNA quantification in individuals at higher risk for HCV (people
who use and inject drugs, sex workers and men who have sex with men) in seven
South African cities.
Methods: Samples were screened on the OraQuick HCV POC test (471 whole blood
and 218 oral fluid); 218 whole blood and DBS paired samples were evaluated on the
ARCHITECT HCV antibody (Abbott) and HCV viral load (COBAS Ampliprep/COBAS
TaqMan version 2) assays. For HCV RNA quantification, 107 dB were analyzed with
and without normalization coefficients.
Results: POC on either whole blood or oral fluid showed an overall sensitivity of
98.5% (95% CI 97.4-99.5), specificity of 98.2% (95% CI 98.8-100) and accuracy of
98.4% (95% CI 96.5-99.3). On the antibody immunoassay, DBS showed a sensitivity
of 96.0% (95% CI 93.4-98.6), specificity of 97% (95% CI 94.8-99.3) and accuracy of
96.3% (95% CI 93.8-98.8). A strong correlation (R2 = 0.90) between viral load measurements
for DBS and plasma samples was observed. After normalization, DBS viral
load results showed an improved bias from 0.5 to 0.16 log10 IU/mL.
Conclusion: The POC test performed sufficiently well to be used for HCV screening in at-risk populations. DBS for diagnosis and quantification was accurate and should
be considered as an alternative sample to test. POC and DBS can help scale up hepatitis
services in the country, in light of our elimination goals.The United States President's Emergency Plan for AIDS Relief, the United States Centers for Disease Control and Prevention, the Bristol-Meyers Squibb Foundation and the Global Fund.https://onlinelibrary.wiley.com/journal/23988835am2022Family Medicin
CD14(+) macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide
Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT).status: publishe