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Oxidative stress, inflammation, and apoptosis have been reported to influence cognitive function in patients with Alzheimer’s disease (AD), particularly those infected with herpes simplex virus type 1 (HSV-1) or cytomegalovirus (CMV). This study aimed to evaluate the effects of viral infection on oxidative stress markers associated with these pathways in AD patients. A total of 100 adults with mild-to-moderate AD were randomly assigned to a double-blind, placebo-controlled clinical trial and categorized into three groups: AD (uninfected), AD with HSV-1, and AD with CMV. The primary outcomes included changes in serum inflammatory markers (IL-1β and TNF-α), blood antioxidant and oxidative stress markers—glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), and total antioxidant capacity (TAC), as well as the expression levels of apoptosis-related proteins (BAX and BCL-2). Results showed that, compared to the control group, the AD group exhibited significant alterations in inflammatory and oxidative stress markers. CMV infection led to increased antioxidant enzyme activity and decreased serum inflammatory markers relative to the uninfected AD group. However, there were significant differences in ratio BAX/BCL-2 protein expression between the CMV and HSV-1 groups when compared to the AD group. In conclusion, AD patients infected with HSV-1 or CMV demonstrated distinct alterations in inflammatory, oxidative stress, antioxidant profiles, and apoptosis markers, which may have beneficial implications for circulatory biomarkers and potentially cognitive outcomes in AD.

Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.

Background Co-infection with malaria and intestinal parasites such as Ascaris lumbricoides is common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection. Ascaris is known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whether Ascaris co-infection can minimize the severity of malarial anaemia. Methods Data from a randomized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged (6–59 months) children conducted in 2006–2007 were analysed to examine the effect of malaria and Ascaris co-infection on anaemia severity. Children were enrolled and tested for malaria, helminths and anaemia at baseline, four, and eight months. Six hundred and ninety subjects were analysed in this study. Generalized linear mixed models were used to assess the relationship between infection status and Ascaris and Plasmodium parasite intensity on severity of anaemia, defined as a haemoglobin less than 11 g/dL. Results Malaria prevalence ranged from 35-78% over the course of this study. Of the malaria-infected children, 55% were co-infected with Ascaris at baseline, 60% were co-infected four months later and 48% were co-infected eight months later, underlining the persistent prevalence of malaria-nematode co-infections in this population. Over the course of the study the percentage of anaemic subjects in the population ranged between 84% at baseline and 77% at the eight-month time point. The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria. Ascaris infection alone did not increase the odds of being anaemic, indicating that malaria was the main cause of anaemia in this population. There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria and Ascaris . Conclusion In this cohort of Nigerian preschool children, malaria infection was the major contributor to anaemia status. Ascaris co-infection neither exacerbated nor ameliorated the severity of malarial anaemia.

Factors increasing genital human immunodeficiency virus (HIV) shedding may increase female-to-male HIV transmission risk. We examined HIV shedding in 67 women with HIV type 1 and herpes simplex virus type 2 coinfection, during 2 menstrual cycles. Shedding occurred in 60%, 48%, and 54% of samples during the follicular, periovulatory, and luteal phases, respectively (P = .01). Shedding declined after menses until ovulation, with a slope -0.054 log 10 copies/swab/day (P < .001), corresponding to a change of approximately 0.74 log 10 copies between peak and nadir levels. Shedding increased during the luteal phase only among women with CD4 counts of <350 cells/μL. In reproductive-aged women, shedding frequency and magnitude are greatest immediately following menses and lowest at ovulation.

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2-specific (SARS-CoV-2-specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non-COVID-19 patients. We showed that SARS-CoV-2-specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1-mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis-specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.

In a large study of children hospitalized with community-acquired pneumonia, virus-bacterium coinfections resulted in worse outcomes than virus-only infections. Patterns of coinfections varied with the pathogen. Abstract Background Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance. Methods We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics. Results A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings. Conclusions Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.

Leishmaniasis is a zoonotic disease in humans caused by the bite of a parasite-infected sandfly. The disease, widely referred to as “poor man’s disease,” affects millions of people worldwide. The clinical manifestation of the disease depends upon the species of the parasite and ranges from physical disfigurement to death if left untreated. Here, we review the past, present, and future of leishmaniasis in detail. The life cycle of Leishmania sp., along with its epidemiology, is discussed, and in addition, the line of therapeutics available for treatment currently is examined. The current status of the disease is critically evaluated, keeping emerging threats like human immunodeficiency virus (HIV) coinfection and post kala-azar dermal leishmaniasis (PKDL) into consideration. In summary, the review proposes a dire need for new therapeutics and reassessment of the measures and policies concerning emerging threats. New strategies are essential to achieve the goal of leishmaniasis eradication in the next few decades.

In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon (IFN) signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV superinfection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic IFN response. Using blood samples of coinfected patients, IFN-stimulated gene products including C-X-C motif chemokine 10 (CXCL10), C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic IFN response following HCV clearance and identify serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV-coinfected persons.

Secondary bacterial pneumonia leads to increased morbidity and mortality from influenza virus infections. What causes this increased susceptibility, however, is not well defined. Host defense from infection relies not only on immune resistance mechanisms but also on the ability to tolerate a given level of pathogen burden. Failure of either resistance or tolerance can contribute to disease severity, making it hard to distinguish their relative contribution. We employ a coinfection mouse model of influenza virus and Legionella pneumophila in which we can separate resistance and tolerance. We demonstrate that influenza virus can promote susceptibility to lethal bacterial coinfection, even when bacterial infection is controlled by the immune system. We propose that this failure of host defense is due to impaired ability to tolerate tissue damage.