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We previously demonstrated that the overall number of regulatory T (Treg) cells decrease proportionately with helper CD4+ T cells and their frequencies increase in antiretroviral therapy (ART)-naive human immunodeficiency virus type-1 (HIV-1) infected individuals. The question now is whether the discrepancies in Treg cell numbers and frequencies are synonymous to an impairment of their functions. To address this, we purified Treg cells and assessed their ability to modulate autologous monocytes functions. We observed that Treg cells were able to down modulate autologous monocytes activation as well as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production during stimulation with polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC). This activity of Treg cells has been shown to be influenced by immunocompetence including but not limited to helper CD4+ T cell counts, in individuals with HIV-1 infection. Compared to immunosuppressed participants (CD4 < 500 cells/µL), immunocompetent participants (CD4 ≥ 500 cells/µL) showed significantly higher levels of transforming growth factor beta (TGF-β) and IL-10 (p < 0.001 and p < 0.05, respectively), key cytokines used by Treg cells to exert their immunosuppressive functions. Our findings suggest the contribution of both TGF-β and IL-10 in the suppressive activity of Treg cells. [ABSTRACT FROM AUTHOR]

Although there are several indirect methods that can be used to verify reference limits, they have a common weakness in that they assume a low proportion of pathological values. This paper investigates whether a Gaussian decomposition algorithm can identify the non-pathological fraction even if it is not the main subset of mixed data. All investigations are carried out in the R programming environment. The mclust package is used for Gaussian mixture modelling via the expectation maximization (EM) algorithm. For right-skewed distributions, logarithms of the original values are taken to approximate the Gaussian model. We use the Bayesian information criterion (BIC) for evaluation of the results. The reflimR and refineR packages serve as comparison procedures. We generate synthetic data mixtures with known normal distributions to demonstrate the feasibility and reliability of our approach. Application of the algorithm to real data from a Nigerian and a German population produces results, which help to interpret reference intervals of reflimR and refineR that are obviously too wide. In the first example, the mclust analysis of hemoglobin in Nigerian women supports the medical hypothesis that an anemia rate of more than 50 % leads to falsely low reference limits. Our algorithm proposes various scenarios based on the BIC values, one of which suggests reference limits that are close to published data for Nigeria but significantly lower than those established for the Caucasian population. In the second example, the standard statistical analysis of creatine kinase in German patients with predominantly cardiac diseases yields a reference interval that is clearly too wide. With mclust we identify overlapping fractions that explain this false result. Gaussian mixture modelling does not replace standard methods for reference interval estimation but is a valuable adjunct when these methods produce discrepant or implausible results. [ABSTRACT FROM AUTHOR]

Background: The parasitic infection caused by Taenia solium represents a significant public health concern in developing countries. Larval invasion of body tissues leads to cysticercosis (CC), while central nervous system (CNS) involvement results in neurocysticercosis (NCC). Both conditions exhibit diverse clinical manifestations, and the potential impact of concomitant HIV infection especially prevalent in sub-Saharan Africa on peripheral and CNS immune responses remains poorly understood. This study aimed to identify the potential impact of HIV coinfection in CC and NCC patients. Methodology: A nested study within a cross-sectional analysis in two Tanzanian regions was performed and 234 participants (110 HIV+ and 124 HIV-) were tested for cysticercosis antibodies, antigens, CD4 counts and serum Th1 and Th2 cytokines via multiplex bead-based immunoassay. 127 cysticercosis seropositive individuals underwent cranial computed tomography (CCT) and clinical symptoms were assessed. Multiple regression analyses were performed to identify factors associated with cytokine modulation due to HIV in CC and NCC patients. Results: Serologically, 18.8% tested positive for cysticercosis antibodies, with no significant difference HIV+ and HIV+. A significantly higher rate of cysticercosis antigen positivity was found in HIV+ individuals (43.6%) compared to HIV- (28.2%) (p = 0.016). CCT scans revealed that overall 10.3% had active brain cysts (NCC+). Our study found no significant changes in the overall cytokine profiles between HIV+ and HIV- participants coinfected CC and NCC, except for IL-5 which was elevated in HIV+ individuals with cysticercosis. Furthermore, HIV infection in general was associated with increased levels of pro-and some anti-inflammatory cytokines e.g. TNF-α, IL-8, and IFN-γ. However, based on the interaction analyses, no cytokine changes were observed due to HIV in CC or NCC patients. Conclusions: In conclusion, while HIV infection itself significantly modulates levels of key cytokines such as TNF-α, IL-8, and IFN-γ, it does not modulate any cytokine changes due to CC or NCC. This underscores the dominant influence of HIV on the immune system and highlights the importance of effective antiretroviral therapy in managing immune responses in individuals coinfected with HIV and CC/NCC. Author summary: Our study evaluates the interplay of immune responses in individuals coinfected with HIV and neurocysticercosis (NCC) in resource-limited settings. We analyzed cytokine profiles among 234 participants, discovering that HIV infection significantly modulates various key cytokines such as TNF-α, IL-8, and IFN-γ. Notably, our results indicate that while HIV has a dominant influence on cytokine levels, it does not cause additional cytokine alterations specifically due to NCC. This suggests that the immunomodulatory effects of NCC are minimal in the presence of HIV, pointing to the overarching impact of HIV on the immune system. Our findings emphasize the complexity of immune responses in coinfected individuals and underscore the critical role of effective antiretroviral therapy. Insights from our study are crucial for refining therapeutic strategies in managing such complex coinfections in endemic regions. [ABSTRACT FROM AUTHOR]

Granuloma is a crucial pathological feature of tuberculosis (TB). The relationship between CD4+ T cells in both peripheral blood and granulomatous tissue, and the integrity of granulomas in Human Immunodeficiency Virus (HIV)–MTB co-infection, remains unexplored. This study collected biopsy specimens from 102 TB patients (53 with HIV-MTB co-infection and 49 only with TB). Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed, followed by microscopic examination of the integrity of tuberculous granulomas. Through statistical analysis of peripheral blood CD4+ T cell counts, tissue CD4+ T cell proportion, and the integrity of granulomas, it was observed that HIV infection leads to poor formation of tuberculous granulomas. Peripheral blood CD4+ T cell counts were positively correlated with granuloma integrity, and there was a similar positive correlation between tissue CD4+ T cell proportions and granuloma integrity. Additionally, a positive correlation was found between peripheral blood CD4+ T cell counts and the proportion of CD4+ T cells in granuloma tissues. Therefore, HIV infection could impact the morphology and structure of tuberculous granulomas, with a reduced proportion of both peripheral blood and tissue CD4+ T lymphocytes. [ABSTRACT FROM AUTHOR]

Coinfection with Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) is a significant public health concern. Individuals infected with Mtb who acquire HIV are approximately 16 times more likely to develop active tuberculosis. T cells play an important role as both targets for HIV infection and mediators of the immune response against both pathogens. This review aims to synthesize the current literature and provide insights into the effects of HIV/Mtb coinfection on T cell populations and their contributions to immunity. Evidence from multiple in vitro and in vivo studies demonstrates that T helper responses are severely compromised during coinfection, leading to impaired cytotoxic responses. Moreover, HIV's targeting of Mtb-specific cells, including those within granulomas, offers an explanation for the severe progression of the disease. Herein, we discuss the patterns of differentiation, exhaustion, and transcriptomic changes in T cells during coinfection, as well as the metabolic adaptations that are necessary for T cell maintenance and functionality. This review highlights the interconnectedness of the immune response and the pathogenesis of HIV/Mtb coinfection. [ABSTRACT FROM AUTHOR]

Developing new anti-human immunodeficiency virus (HIV) drug candidates that target different sites in HIV-1 replication, with better resistance profiles and lower drug toxicity, is essential to eradicating HIV. This study investigated the potential of fractionated crude extracts of Alternaria alternata as immunomodulatory or anti-HIV drug candidates. Solid-phase extraction (SPE) was used to fractionate A. alternata PO4PR2 using three different columns: MAX (Mixed-mode, strong Anion-eXchange), MCX (Mixed-mode, strong Cation-eXchange), and HLB (Hydrophilic–Lipophilic Balance) with methanol gradient methods (5%, 45%, and 95%). An MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to assess the cell viability and cytotoxicity of the fractionated crude extract A. alternata PO4PR2 in the TZM-bl cell lines. This was followed by a luciferase-based antiviral assay to assess the antiviral activity of A. alternata PO4PR2. A time of addition (TOA) assay was performed to ascertain the mechanism of inhibition employed by the fractionated crude extract of A. alternata PO4PR2 in the HIV life cycle. The p24 titer was determined using an ELISA, while a luciferase-based antiviral assay was used to evaluate the HIV percentage inhibition for different HIV-1 replication cycles. The TOA assay was established using antiviral drugs that target different sites in the HIV replication cycle. These included maraviroc, azidothymidine, raltegravir, and amprenavir. The immunomodulatory effect of the fractionated crude extracts on CD4+ T cells was measured by a flow cytometric analysis, for which fluorochrome-labelled monoclonal antibodies were used as markers for activation (CD38 and HLA-DR) and exhaustion (PD-1). The MCX fraction demonstrated a more significant anti-HIV inhibition than that of the fractions generated in other columns, with an IC50 of 0.3619 µg/mL, an HIV inhibition of 77%, 5% HLB (IC50: 0.7232 µg/mL; HIV inhibition of 64%), and 5% MAX (IC50: 5.240 µg/mL; HIV inhibition of 67%). It was evident from the time of addition data that the crude extract and the 5% MCX fraction inhibited viral binding (68%), reverse transcription (75%), integration (98%), and proteolysis (77%). It was shown that A. alternata (the MCX fraction) have a significant inhibitory effect on reverse transcription (75% HIV inhibition) and integration (100% HIV inhibition). The 5% MCX (p = 0.0062), 5% HLB (p = 0.0269), and 5% MAX (p = 0.0117) fractionated A. alternata crude extracts had low levels of CD4+ T cell (CD38 + HLA-DR+) activation compared to those of the AZT treatment, while CD4+ T cell activation was insignificant. The 5% MAX and HLB A. alternata fractions may possess immunomodulatory compounds with less anti-HIV-1 activity. A. alternata could be a key source of innovative anti-HIV drugs with immunomodulatory characteristics. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a prevalent infectious disease affecting populations worldwide. A classic trait of TB pathology is the formation of granulomas, which wall off the pathogen, via the innate and adaptive immune systems. Some key players involved include tumor necrosis factor-alpha (TNF-α), foamy macrophages, type I interferons (IFNs), and reactive oxygen species, which may also show overlap with cell death pathways. Additionally, host cell death is a primary method for combating and controlling Mtb within the body, a process which is influenced by both host and bacterial factors. These cell death modalities have distinct molecular mechanisms and pathways. Programmed cell death (PCD), encompassing apoptosis and autophagy, typically confers a protective response against Mtb by containing the bacteria within dead macrophages, facilitating their phagocytosis by uninfected or neighboring cells, whereas necrotic cell death benefits the pathogen, leading to the release of bacteria extracellularly. Apoptosis is triggered via intrinsic and extrinsic caspase-dependent pathways as well as caspase-independent pathways. Necrosis is induced via various pathways, including necroptosis, pyroptosis, and ferroptosis. Given the pivotal role of host cell death pathways in host defense against Mtb, therapeutic agents targeting cell death signaling have been investigated for TB treatment. This review provides an overview of the diverse mechanisms underlying Mtb-induced host cell death, examining their implications for host immunity. Furthermore, it discusses the potential of targeting host cell death pathways as therapeutic and preventive strategies against Mtb infection. [ABSTRACT FROM AUTHOR]

Congenital syphilis presents a significant global burden, contributing to fetal loss, stillbirth, neonatal mortality, and congenital infection. Despite the target established in 2007 by the World Health Organization (WHO) of fewer than 50 cases per 100,000 live births, the global incidence is on the rise, particularly in low- and middle-income regions. Recent data indicate a rate of 473 cases per 100,000 live births, resulting in 661,000 total cases of congenital syphilis, including 355,000 adverse birth outcomes such as early fetal deaths, stillbirths, neonatal deaths, preterm or low-birth-weight births, and infants with clinical congenital syphilis. Alarmingly, only 6% of these adverse outcomes occurred in mothers who were enrolled, screened, and treated. Unlike many neonatal infections, congenital syphilis is preventable through effective antenatal screening and treatment of infected pregnant women. However, despite available screening tools, affordable treatment options, and the integration of prevention programs into antenatal care in various countries, congenital syphilis remains a pressing public health concern worldwide. This review aims to summarize the current epidemiology, transmission, and treatment of syphilis in pregnancy, as well as to explore global efforts to reduce vertical transmission and address the reasons for falling short of the WHO elimination target. [ABSTRACT FROM AUTHOR]

Background: Clinical outcomes of ascariasis, one of the most common parasitic infections, are remarkably variable ranging from asymptomatic infection to death. Ascariasis can pair absorption of fats, vitamin A, iodine, and lactose digestion and destroys the villi, with significant consequences in pregnancy outcomes, leading to growth retardation, and cognitive impairment, decreased work capacity, and adverse pregnancy outcomes. One of the crucial factors driving the clinical outcomes of ascariasis is the immune response and associated oxidative stress. This study therefore examined the prevalence of ascariasis and associated immune response dysfunction by measuring four inflammatory cytokines alongside with the oxidant and antioxidant biomarkers in women of reproductive age in a health center in Cameroon. Results: Three-hundred and fifty-five women (pregnant and non-pregnant) were examined for the parasite. Because some participants did not donate blood and due to low volume of blood available, only 127 individuals (62 non-pregnant women and 65 pregnant women) were included for analysis of oxidative biomarkers, and 90 samples were used for the evaluation of inflammatory biomarkers (40 non-pregnant and 50 pregnant). The prevalence of Ascaris lumbricoides was of 13.23%. Ascariasis was associated with high levels in inflammatory cytokines (IL-1β, IL-12, IL-10, and TNF-α) and oxidative markers (TOS, OSI, MDA, and CAT) in both pregnant and non-pregnant women, while high level of NO was only seen in pregnant women. A significant relation was observed between some cytokines and oxidant markers: IL-10 and OSI and IL-12 and NO and between IL-1β and MDA in pregnant women, while in non-pregnant, significant relation was found between Il-10 and NO as well as IL-1β and OSI and NO. Principal component analysis (PCA) underlined a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-10, TNF-α). PCA also highlighted an oxidative stress with strongest contributions from TOS, OSI, SOD, NO, and CAT in pregnant and from OSI, TOS, NO, CAT, and TAC in non-pregnant. Conclusion: These findings demonstrate elevated cytokines (IL-1β, IL-12, IL-10, and TNF-α) and high oxidative stress imbalance, adding further evidence for the role of a pro-inflammatory cytokine signature of oxidative stress in women with A. lumbricoides. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combating the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials. [ABSTRACT FROM AUTHOR]

Background: In Burkina Faso, the prevalence of malaria has decreased over the past two decades, following the scale-up of control interventions. The successful development of malaria parasites depends on several climatic factors. Intervention gains may be reversed by changes in climatic factors. In this study, we investigated the role of malaria control interventions and climatic factors in influencing changes in the risk of malaria parasitaemia. Methods: Bayesian logistic geostatistical models were fitted on Malaria Indicator Survey data from Burkina Faso obtained in 2014 and 2017/2018 to estimate the effects of malaria control interventions and climatic factors on the temporal changes of malaria parasite prevalence. Additionally, intervention effects were assessed at regional level, using a spatially varying coefficients model. Results: Temperature showed a statistically important negative association with the geographic distribution of parasitaemia prevalence in both surveys; however, the effects of insecticide-treated nets (ITNs) use was negative and statistically important only in 2017/2018. Overall, the estimated number of infected children under the age of 5 years decreased from 704,202 in 2014 to 290,189 in 2017/2018. The use of ITNs was related to the decline at national and regional level, but coverage with artemisinin-based combination therapy only at regional level. Conclusion: Interventions contributed more than climatic factors to the observed change of parasitaemia risk in Burkina Faso during the period of 2014 to 2017/2018. Intervention effects varied in space. Longer time series analyses are warranted to determine the differential effect of a changing climate on malaria parasitaemia risk. [ABSTRACT FROM AUTHOR]

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Drug repurposing is an ongoing and clever strategy that is being developed to eradicate tuberculosis amid challenges, of which one of the major challenges is the resistance developed towards antibiotics used in standard directly observed treatment, short-course regimen. Surpassing the challenges in developing anti-tuberculous drugs, some novel host-directed therapies, repurposed drugs, and drugs with novel targets are being studied, and few are being approved too. After almost 4 decades since the approval of rifampicin as a potent drug for drugsusceptible tuberculosis, the first drug to be approved for drug-resistant tuberculosis is bedaquiline. Ever since the urge to drug discovery has been at a brisk as this milestone in tuberculosis treatment has provoked the hunt for novel targets in tuberculosis. Host-directed therapy and repurposed drugs are in trend as their pharmacological and toxicological properties have already been researched for some other diseases making the trial facile. This review discusses the remonstrance faced by researchers in developing a drug candidate with a novel target, the furtherance in tuberculosis research, novel anti-tuberculosis agents approved so far, and candidates on trial including the host-directed therapy, repurposed drug and drug combinations that may prove to be potential in treating tuberculosis soon, aiming to augment the awareness in this context to the imminent researchers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)