Outcome markers of ART-treated HIV+ patients with early stage Kaposi’s sarcoma

HIV-associated/epidemic Kaposi’s sarcoma (EpKS) is an AIDS-defining angio-proliferative malignancy. It can be treated with antiretroviral therapy (ART) alone or with ART plus cytotoxic chemotherapy. ART-treated EpKS can either respond or worsen upon treatment. This study aimed at identifying immunological markers of ART-treatment response. We compared responders (those with clinical EpKS tumor regression) versus poor responders (those with progressive or non-responsive EpKS). We measured plasma cytokine and chemokine levels using cytometric bead assays. Kaposi’s sarcoma herpesvirus (KSHV) neutralizing antibody (nAb) responses were also quantified to test associations with treatment outcome. Interleukin (IL)-5 levels were significantly elevated in responders versus poorresponders at baseline (0.76pg/ml vs. 0.37pg/ml; p\u3c0.01) and follow-up (0.56pg/ml vs. 0.37pg/ml; p\u3c0.01); IL-6 was lower in responders than poor-responders at follow-up (600fg/ ml vs. 4272fg/ml; p\u3c0.05). IP-10/CxCL-10 was significantly lower at follow-up in responders versus poor-responders (187pg/ml vs. 528pg/ml; p\u3c0.01). KSHV nAb were not significantly differential between responders and poor-responders. In conclusion, high plasma IL-5 at baseline could be a marker for ART-treated KS tumor regression, whereas increased proinflammatory cytokine IL-6, and the chemokine IP-10, associate with KS tumor progression

HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals

Background: High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. Methods: We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. Results: The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and nondipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001). Conclusions: The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this

Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia.

INTRODUCTION: Rotavirus vaccines have been introduced into national immunization programmes to mitigate morbidity and mortality associated rotavirus diarrhoea. Lower vaccine effectiveness has however been noted in low-middle income countries, but little is known about the role of maternal components found in breast milk. This study assessed the effect of lactoferrin, lactadherin, and tenascin-c on rotavirus vaccine seroconversion. METHODS: This was a retrospective cohort study of 128 infants who had been fully immunized with Rotarix™. Serum samples were collected from the infant at baseline and one month after second rotavirus vaccine dose. Breast milk samples were collected from mothers at baseline. Standard ELISA was used to determine titres of rotavirus-specific immunologlobulin G and A in breast milk and serum as well as concentrations of lactoferrin, lactadherin, and tenascin-c. Poisson regression model with robust standard error was used to estimate the effect of breast milk components on seroconversion. The components were modelled on log base 2 so that the effect would be interpreted as a doubling of the concentration. RESULTS: In a multivariable analysis adjusting for maternal age, maternal HIV status, seropositivity at baseline, sex, age of child at vaccination as well as breast milk IgA and IgG, we found evidence of independent effect of LA (Adjusted IRR = 0.95; 95% CI = 0.91-0.99; P = 0.019) on seroconversion while there was no evidence for TNC (Adjusted IRR = 1.00; 95% CI = 0.85-1.17; P = 0.967) and LF (Adjusted RR = 1.01; 95% CI = 0.96-1.05); P = 0.802). We explored the joint effects of the three components but we found no evidence (Adjusted RR = 0.95; 95% CI = 0.81; P = 0.535). CONCLUSION: High breast milk concentrations of lactadherin might play a role in infant's failure to seroconvert to rotavirus vaccines. Further research to understand this observed association is an important consideration

Immediate pressor response to oral salt and its assessment in the clinic: a time series clinical trial

Background: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor efect of salt is viewed as a chronic efect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this efect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments. Methods: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2g of sodium chloride; their BP was monitored for 120minutes in intervals of 10minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data. Results: Median age was 30 years (interquartile range, 22–46 years) and 52% were female patients. An increase of ≥10mmHg in mean arterial pressure (MAP), considered a clinically signifcant IPROS, was present in 62% of participants. Systolic BP 30minutes after the salt load was a signifcant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting. Conclusions: We confrm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral saltloads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our fndings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP

Awareness and acceptance of COVID-19 vaccines and associated factors among pharmacy students in Zambia

Background: Several vaccines have been developed and administered since coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. In April 2021, the authorities in Zambia administered the first doses of the Oxford-AstraZeneca® COVID-19 vaccine. Objective: To assess the awareness and acceptance of COVID-19 vaccines and associated factors among pharmacy students in Zambia. Methods: A cross-sectional study among 326 undergraduate pharmacy students in Lusaka, Zambia, from February through to 25 April 2021. Data were analysed using Stata version 16.1. Multivariable logistic regression was used to determine factors influencing vaccine acceptance. Results: Of the 326 participants, 98.8% were aware of the COVID-19 vaccines, but only 24.5% would accept vaccination. Being of Christian faith was associated with reduced odds of awareness of the COVID-19 vaccine (aOR=0.01; 95% CI: 0.01-0.20). Compared to females, male respondents were 86% more likely to accept the vaccine if it was made available (aOR=1.86; 95% CI: 1.10-3.14). Unmarried compared to married respondents were 2.65 times as likely to accept vaccination (aOR=2.65; 95% CI: 1.06-6.63) whilst unemployed respondents were less likely to accept vaccination (aOR=0.32; 95% CI: 0.16-0.46). Barriers to the acceptability of the vaccine were possible side effects (78.5%) and scepticism about its effectiveness to prevent COVID-19 (10.2%). Conclusion: There was significant vaccine hesitancy toward COVID-19 vaccines among Zambian pharmacy students despite their awareness of the vaccines. Health authorities must work collaboratively with training institutions to mitigate vaccine hesitancy, especially with healthcare students being a key part of the future healthcare workforce overseeing disease prevention strategies

Towards a competency-based doctoral curriculum at the University of Zambia: lessons from practice

We describe a collaborative, iterative, and participatory process that we undertook to develop and adopt a competency-based doctoral curriculum framework at the University of Zambia. There needs to be more than the traditional unstructured apprenticeship of PhD training in a knowledge-based economy where PhD graduates are expected to contribute to industry problem-solving. The lack of industry-driven competencies and, to some extent, limited skills possessed by PhD graduates relative to the demands of employers has led to the misclassification of doctoral degrees as mere paper certificates. Further, under traditional PhD training without specific core competencies, it has led to criticisms of such PhD studies as a waste of resources. The calls to rethink doctoral development in broader employment contexts led many countries to redesign their PhD programs. Training has increasingly introduced industrial linkages and industry-defined research projects to increase the attractiveness of doctoral students. Whereas developed countries have made significant reforms towards competency-based PhD training, little or nothing has been done in developing countries, especially in sub-Saharan Africa. This against the demands that Africa needs more than 100,000 PhDs in the next decade to spur economic development. Against this background, the University of Zambia has developed an industry-driven structured competency-based PhD curriculum framework. The framework will guide and support the development of standardized program-specific PhD curricula, delivery, and assessment of competencies at the University of Zambia, ensuring that doctoral students acquire skills and demonstrate core competencies that are transferable and applicable in industry settings. This framework focuses on the development of specific competencies that are necessary for successful PhD completion. The competencies are divided into three main categories: research, teaching, and professional development. Each category is then broken down into ten core competencies from which respective doctoral programs will develop sub-competencies. It is from these core competencies and sub-competencies that learning outcomes, assessment methods, and teaching activities are developed. It is envisioned that this new competency-based doctoral curriculum framework will be a helpful tool in training a cadre of professionals and researchers who benefit the industry and contribute to economic and societal development

Luna Virus and Helminths in Wild Mastomys natalensis in Two Contrasting Habitats in Zambia: Risk Factors and Evidence of Virus Dissemination in Semen

Transmission dynamics and the maintenance of mammarenaviruses in nature are poorly understood. Using metagenomic next-generation sequencing (mNGS) and RT-PCR, we investigated the presence of mammarenaviruses and co-infecting helminths in various tissues of 182 Mastomys natalensis rodents and 68 other small mammals in riverine and non-riverine habitats in Zambia. The Luna virus (LUAV) genome was the only mammarenavirus detected (7.7%; 14/182) from M. natalensis. Only one rodent from the non-riverine habitat was positive, while all six foetuses from one pregnant rodent carried LUAV. LUAV-specific mNGS reads were 24-fold higher in semen than in other tissues from males. Phylogenetically, the viruses were closely related to each other within the LUAV clade. Helminth infections were found in 11.5% (21/182) of M. natalensis. LUAV-helminth co-infections were observed in 50% (7/14) of virus-positive rodents. Juvenility (OR = 9.4; p = 0.018; 95% CI: 1.47-59.84), nematodes (OR = 15.5; p = 0.001; 95% CI: 3.11-76.70), cestodes (OR = 10.8; p = 0.025; 95% CI: 1.35-86.77), and being male (OR = 4.6; p = 0.036; 95% CI: 1.10-18.90) were associated with increased odds of LUAV RNA detection. The role of possible sexual and/or congenital transmission in the epidemiology of LUAV infections in rodents requires further study, along with the implications of possible helminth co-infection

Characterization of HIV-1 binding to peripheral blood mononuclear cells versus monocytes/macrophages : relationship to neuropathogenesis

Thesis (M.S.)--University of Hawaii at Manoa, 2007.Includes bibliographical references (leaves 57-63).xii, 63 leaves, bound col. ill. 29 cmIndividuals with HIV-1-associated dementia (HAD) are characterized with increased percentages of circulating activated monocytes/macrophages (M/MΦ) with CDl4/CDl6 phenotype. Higher levels of HIV-1 DNA are detected in these activated cells, thus hypothesizing that the activated M/MΦ have higher viral binding and possibly leading to more permissive infectivity. From a non-HIV-I-infected volunteer, peripheral blood mononuclear cells (PBMCs), magnetic bead-separated activated and non-activated monocytes were exposed to 2ng p24 units of LAI (X4 Strain) and p89.6 (dual tropic but preferentially X5 strain) for one hour at 37°C, 5% CO2. Viral binding capacity was assayed by RT-PCR using HIV Gag and β-actin primers with appropriate positive and negative control RNA and densitometry. Differences in binding capacities between each of the two groups were considered significant by Student's t-test and One-Way ANOVA if p<0.05. As expected, M/MΦ displayed a higher HIV-1 binding to p89.6 than to LAI, 0.497 vs. 0.328 (p=0.025), respectively. In the PBMCs, viral binding capacity was increased compared to M/MΦ , for LAI: 0.492 vs. 0.328, respectively (p=0.011); for p89.6: 0.878 vs. 0.497, respectively (p=0.004). Of note was the significantly higher binding found with p89.6 (0.878) compared to LAI (0.492) (p=0.004), since the PBMCs were from the same volunteer obtained at the same time. There was a trend for HIV-1 binding to be higher for activated monocytes [LAI (0.324), P89.6 (0.277)] compared to non-activated monocytes [LAI (0.22S), p89.6 (0.249)], p= 0.362. These results demonstrate that peripheral M/MΦ preferentially bind CCRS virus suggesting that the high HIV DNA found in PBMCs represents bound virus on the M/MΦ subset. The enhanced binding of CCR5 strains to M/MΦ , particularly to activated M/MΦ , may lead to more permissive infection of this subset. The theory that increased trafficking of HIV-1-infected activated M/MΦ to the central nervous system is consistent with the findings

Effects of marijuana on peripheral and central nervous immune markers in marijuana smokers and HIV-infected subjects

Ph.D. University of Hawaii at Manoa 2012.Includes bibliographical references.Marijuana can lower cellular immune responses and inhibit inflammation. The goal of this dissertation was to examine the effects of marijuana on peripheral and central nervous system (CNS) immune markers in current marijuana users (MJ) and HIV-infected marijuana users (HIV+MJ). We hypothesized that marijuana would lower cell activation and reduce inflammatory cytokine secretion in the CNS. An in vitro monocyte activation model using lipopolysaccharide was developed to assess baseline and activation immune markers in healthy individuals using flow cytometry and the kinetics of HIV infection between activated and non-activated monocytes was studied. Peripheral blood mononuclear cells were isolated from HIV+MJ, HIV+ subjects (HIV+), MJ and sero-negative controls (SN). Cells were stained for cannabinoid receptors (CB) and immune markers and were analyzed using flow cytometry. Cytokines from age-matched subjects who provided cerebral spinal fluid (CSF) were measured by Luminex. After lipopolysaccharide stimulation, monocytes increased CD16 and CD69 surface expression (p<0.05). The activated monocyte phenotype was supported by an increase in TNF-α production (p<0.05). The activated monocytes also had increased CCR5 expression (p=0.05) and bound more R5-tropic HIV than non-activated monocytes (p<0.05). CB1 and CB2 receptors were found on monocytes and significant group differences were observed in the expression of inflammatory CD16 (p<0.0001) and CCR5 (p<0.003) on monocytes. CD14+CD16+ monocytes were higher in HIV+MJ than in HIV+ subjects (p=0.0054), and in MJ users than in SN subjects (p<0.0001). CCR5 expression was significantly higher in MJ users than SN subjects (p<0.0001); however, no difference in CCR5 expression was found between HIV+MJ users and HIV subjects (p=0.4). The duration of marijuana use correlated with the levels of CD14+CD16+ (r=0.53, p<0.001) and CD14+CCR5+ expression (r=0.24, p=0.049). Inflammatory cytokines (fractalkine, INF-α2 and IL-1α) and chemoattractants (MCP-1, IP-10 and IL-8) were all significantly higher in the HIV+MJ and MJ than in respective controls. The higher levels of inflammatory cytokines and activated monocytes in HIV+MJ and MJ groups, as well as their correlation with lifetime MJ use, suggest marijuana induced inflammation in the periphery and CNS. Moreover, higher CCR5 expression on the activated monocytes in MJ suggests that marijuana use may render susceptibility to HIV infection

Cells of the Innate and Adaptive Immune Systems in Kaposi’s Sarcoma

Kaposi’s sarcoma (KS) is an angioproliferative malignancy whose associated etiologic agent is the Kaposi’s sarcoma-associated herpesvirus (KSHV). KS is the most prevalent malignancy among HIV-infected individuals globally and is considered an AIDS-defining malignancy. The different forms of KS including HIV-associated KS, iatrogenic (immunosuppression-related) KS, and classical KS in elderly males suggest that immune cell dysregulation is among the key components in promoting KS development in KSHV-infected individuals. It is therefore expected that different cell types of the immune system likely play distinct roles in promoting or inhibiting KS development. This narrative review is focused on discussing cells of the innate and adaptive immune systems in KSHV infection and KS pathogenesis, including how these cells can be useful in the control of KSHV infection and treatment of KS