scholarly journals Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262454
Author(s):  
Patrick Lungu ◽  
Evarist Njelesani ◽  
Thomas Sukwa ◽  
Owen Ngalamika ◽  
Sody Munsaka ◽  
...  

Background People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. Results We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28–42) years and 31(25–36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465–702.5 cells/mm3] vs 345 [157–483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827–23,686 pg/ml] vs. 9,508 [5,514–15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990–24,206 pg/ml] vs 9,505 [5,400–15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087–22,584 pg/ml] vs 10,413 [7,397–14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36–0.72; p < 0.0001) and r = 0.48 (95% CI 0.15–0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0–0.28] vs 0.007 [0–0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. Conclusions This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.

Author(s):  
Kamal K. Sawlani ◽  
Sushrut Singh ◽  
Shyam C. Chaudhary ◽  
D. Himanshu Reddy ◽  
Kauser Usman ◽  
...  

Background: Data on the prevalence of osteoporosis in HIV patients in Asian population is scarce this study was done to find out the prevalence of osteoporosis in HIV infected patients and its correlation with CD4 counts.Methods: This cross- sectional study was conducted in NACO- ART center of tertiary care hospital. Total 115 HIV patients were included in this study which were divided into ART naive (n= 69) and patients taking ART (n= 46). We analysed BMD by DEXA in 115 HIV positive patients and 78 HIV negative age and sex matched controls. Correlation of BMD with a CD4 count and ART regimen was studied.Results: BMD was found to be low in HIV positive patients. T score in HIV positive patients was significantly lower (p<0.05) as compared to the HIV negative control group. The prevalence of osteopenia and osteoporosis in HIV positive patients was 50.4% and 29.6% respectively, as compared to 23.1% and 2.6% in HIV negative controls. BMD showed relation with CD4 count. We did not find any statistical difference between any ART regimen and BMD.Conclusions: The prevalence of osteopenia and osteoporosis in HIV infected cases was higher as compared to HIV negative controls and higher in ART group as compared to ART naïve group. Low BMD levels show correlation with low CD4 count. We recommend that HIV positive patients especially with advanced stage of disease, low CD4 count should be screened for low BMD by DEXA scan for osteoporosis and managed accordingly


2020 ◽  
Vol 8 (4) ◽  
pp. 283-290
Author(s):  
A. Amoko ◽  
P.O. Ajiboye ◽  
F.A. Olagunju ◽  
R.O. Shittu

Objective: Depression is a common mental health problem among people living with HIV/AIDS (PLWHA); because low count of lymphocytes with  cluster of differentiation 4 (CD4 cell count) is associated with severe symptoms of HIV infection, there are thoughts that low CD4 cells count can provoke depressive illness. This study was conducted to determine the relationship between CD4 count and depression among adult HIV positivepatients attending Family Medicine clinics at University of Ilorin Teaching Hospital (UITH), Ilorin, Nigeria.Method: A hospital based descriptive cross-sectional study was done over a period of 6 months among 350 systematically randomly selected adult HIV-positive patients. PHQ-9 was used to obtain information on depression and the CD4 count was determined using a flow-cytometric method. Data were obtained and analyzed using SPSS-17. Chi-square was used to determine degree of association between the depression and the level of CD4 count. P-value of < 0.05 was considered statistically significant.Results: The prevalence of depression among the respondents was 33.4%. The prevalence of depression was highest among respondents with low CD4 count (≤349cells/ul), 37.0%, and least among those with high CD4 count (≥500cells/ul), 28.3%. This relationship was however not statistically significant.Conclusion: The overall prevalence of depression was high among the respondents (33.4%) suggesting the need for routine depression screening among HIV positive patients. There was no statistically significant association between presence of depression and level of CD4 count (p-value=0.302). Keywords: Depression, CD4count, PLWHA, Family Medicine, UITH.


2022 ◽  
Vol 14 (1) ◽  
pp. 43-55
Author(s):  
Cristina Micali ◽  
Ylenia Russotto ◽  
Grazia Caci ◽  
Manuela Ceccarelli ◽  
Andrea Marino ◽  
...  

Hepatocellular carcinoma (HCC) accounts for approximately 75–90% of primary liver cancers and is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. In the HIV-positive population, the risk of HCC is approximately four times higher than in the general population, with higher cancer-specific mortality than in HIV-negative patients. In most cases, HCC diagnosis is made in patients younger than the HIV-negative population and in the intermediate-advanced stage, thus limiting the therapeutic possibilities. Treatment choice in HIV-positive patients with HCC is subject to cancer staging, liver function and health status, as for HIV-negative and non-HIV-negative HCC patients. There are relatively few studies on the efficacy and safety in HIV-positive patients to date in loco-regional treatments for HCC. So far, literature shows that curative treatments such as radiofrequency ablation (RFA) have no significant differences in overall survival between HIV-positive and HIV-negative patients, as opposed to palliative treatments such as TACE, where there is a significant difference in overall survival. Although it can be assumed that the most recently discovered loco-regional therapies are applicable to HIV-positive patients with HCC in the same way as HIV-negative patients, further studies are needed to confirm this hypothesis. The purpose of our review is to evaluate these treatments, their efficacy, effectiveness, safety and their applicability to HIV-positive patients.


2015 ◽  
Vol 83 (5) ◽  
pp. 2118-2126 ◽  
Author(s):  
Truc Hoang ◽  
Else Marie Agger ◽  
Joseph P. Cassidy ◽  
Jan P. Christensen ◽  
Peter Andersen

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse ofMycobacterium tuberculosis, as well as increased pathology, in bothMycobacterium bovisBCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ+TNF-α+and IFN-γ+cells). PEM duringM. tuberculosisinfection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine againstM. tuberculosisinfection.


2013 ◽  
Vol 81 (10) ◽  
pp. 3750-3756 ◽  
Author(s):  
Arjan van Laarhoven ◽  
Jornt J. Mandemakers ◽  
Johanneke Kleinnijenhuis ◽  
Mimount Enaimi ◽  
Ekta Lachmandas ◽  
...  

ABSTRACTOne of the most widespread clades ofMycobacterium tuberculosisworldwide, the Beijing genotype family, consists of ancient (atypical) and modern (typical) strains. Modern Beijing strains outcompete ancient strains in terms of prevalence, while reserving a higher degree of genetic conservation. We hypothesize that their selective advantage lies in eliciting a different host immune response. Bead-disrupted lysates of a collection of differentM. tuberculosisstrains of the modern (n= 7) or ancient (n= 7) Beijing genotype, as well as the Euro-American lineage (n= 6), were used for induction ofex vivocytokine production in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals. Hierarchical clustering and multivariate regression analyses were used to study possible differences in production of nine cytokines. Modern and ancientM. tuberculosisBeijing genotypes induced different cytokine signatures. Overall induction of interleukin-1β (IL-1β), gamma interferon (IFN-γ), and IL-22 was 38 to 40% lower after stimulation with modern Beijing strains (correctedPvalues of <0.0001, 0.0288, and 0.0002, respectively). Euro-American reactivation strains induced 2-fold more TNF-α production than both types of Beijing strains. The observed differences in cytokine induction point to a reduction in proinflammatory cytokine response as a possible contributing factor to the evolutionary success of modern Beijing strains.


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