Global seroprevalence of scrub typhus: a systematic review and meta-analysis.

Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia-Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27-26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05-53.40) for males and 48.84% (45.87-51.80) for females. Eschar prevalence was observed to be 30.34% (22.54-38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions.

Global prevalence of asymptomatic dengue infections - a systematic review and meta-analysis.

OBJECTIVES: The burden of asymptomatic dengue infections is understudied. Therefore, we systematically reviewed the literature to estimate the global prevalence of asymptomatic dengue infections. METHODS: We searched cross-sectional studies reporting the prevalence of asymptomatic dengue infections from PubMed, Scopus, and Embase. Prevalence of asymptomatic dengue infections was pooled and reported as proportions with a 95% confidence interval (CI). This systematic review protocol was a priori registered in The International Prospective Register of Systematic Reviews (Reg: No. CRD42020218446). RESULTS: We included 41 studies with 131,953 cases in our analysis. The overall pooled prevalence of asymptomatic dengue infections was 59.26% (95% CI: 43.76-74.75, I2 = 99.93%), with 65.52% (95% CI: 38.73-92.32, I2 = 99.95%) during outbreaks and 30.78% (95% CI: 21.39-40.16, I2 = 98.78%) during non-outbreak periods. The pooled prevalence among the acutely infected individuals was 54.52% (95% CI: 17.73-46.76, I2 = 99.91%), whereas, among primary and secondary asymptomatic dengue infections, it was 65.36% (95% CI: 45.76-84.96, I2 = 98.82) and 48.99% (95% CI: 27.85-70.13, I2 = 99.08%) respectively. CONCLUSION: The majority of dengue cases are asymptomatic and may play a significant role in disease transmission. Public health strategies aimed at dengue outbreak response and mitigation of disease burden should include early detection of asymptomatic cases.

Immune Cell Cross Talk in the Establishment of Human Immunodeficiency Virus-1 Latency.

Revolutionary progress in combinational antiretroviral therapy has transformed human immunodeficiency virus (HIV) infection into a chronic manageable disease; yet, there exists an uneasy truce between the virus and the immune cells, where inflammation is limited but infection continues to fester from latent reservoirs of the virus. Clinical studies have identified the major immune cell types that constitute the latent HIV-1 reservoirs as monocytes/macrophages and CD4+ T cells. Latency probing approaches have thrown some light on the interaction between the virus and the reservoir cells from the time of onset of infection. However, research combining latency reversal strategies and immunotherapies face daunting obstacles in clinical trials because of the lack of in-depth knowledge on viral pathogenesis and mechanisms of viral evasion, leaving us behind in the battle for HIV cure. This article reviews existing knowledge on the cells and mechanisms that contribute to the establishment and survival of HIV reservoirs in infected individuals.

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy.

Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years (n = 22) and matched HIV-negative healthy individuals (n = 22, HC herein). Untargeted metabolite profiling was carried out using ultra-high-performance liquid chromatography/mass spectrometry/mass spectrometry (UHPLC/MS/MS). Plasma proteomics profiling was performed using proximity extension assay targeting 184 plasma proteins. A total of 250 metabolites differed significantly (p < 0.05, q < 0.1) between PLHIV and HC. Plasma levels of several essential amino acids except for histidine, branched-chain amino acids, and aromatic amino acids (phenylalanine, tyrosine, tryptophan) were significantly lower in PLHIV compared to HC. Machine-learning prediction of metabolite changes indicated a higher risk of inflammatory and neurological diseases in PLHIV. Metabolic abnormalities were observed in amino-acid levels, energetics, and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).

HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease.

With the success of antiretroviral therapy (ART), a dramatic decrease in viral burden and opportunistic infections and an increase in life expectancy has been observed in human immunodeficiency virus (HIV) infected individuals. However, it is now clear that HIV- infected individuals have enhanced susceptibility to non-AIDS (Acquired immunodeficiency syndrome)-related complications such as cardiovascular disease (CVD). CVDs such as atherosclerosis have become a significant cause of morbidity and mortality in individuals with HIV infection. Though studies indicate that ART itself may increase the risk to develop CVD, recent studies suggest a more important role for HIV infection in contributing to CVD independently of the traditional risk factors. Endothelial dysfunction triggered by HIV infection has been identified as a critical link between infection, inflammation/immune activation, and atherosclerosis. Considering the inability of HIV to actively replicate in endothelial cells, endothelial dysfunction depends on both HIV-encoded proteins as well as inflammatory mediators released in the microenvironment by HIV-infected cells. Indeed, the HIV proteins, gp120 (envelope glycoprotein) and Tat (transactivator of transcription), are actively secreted into the endothelial cell micro-environment during HIV infection, while Nef can be actively transferred onto endothelial cells during HIV infection. These proteins can have significant direct effects on the endothelium. These include a range of responses that contribute to endothelial dysfunction, including enhanced adhesiveness, permeability, cell proliferation, apoptosis, oxidative stress as well as activation of cytokine secretion. This review summarizes the current understanding of the interactions of HIV, specifically its proteins with endothelial cells and its implications in cardiovascular disease. We analyze recent in vitro and in vivo studies examining endothelial dysfunction in response to HIV proteins. Furthermore, we discuss the multiple mechanisms by which these viral proteins damage the vascular endothelium in HIV patients. A better understanding of the molecular mechanisms of HIV protein associated endothelial dysfunction leading to cardiovascular disease is likely to be pivotal in devising new strategies to treat and prevent cardiovascular disease in HIV-infected patients.