Experimental depletion of CD8+ cells in acutely SIVagm-Infected African Green Monkeys results in increased viral replication

<p>Abstract</p> <p>Background</p> <p><it>In vivo </it>CD8⁺cell depletions in pathogenic SIV infections identified a key role for cellular immunity in controlling viral load (VL) and disease progression. However, similar studies gave discordant results in chronically-infected SMs, leading some authors to propose that in natural hosts, SIV replication is independent of cellular immunity. To assess the role of cellular immune responses in the control of SIV replication in natural hosts, we investigated the impact of CD8⁺cell depletion during acute SIV infection in AGMs.</p> <p>Results</p> <p>Nine AGMs were infected with SIVagm.sab and were followed up to day 225 p.i. Four were intravenously infused with the cM-T807 antibody on days 0 (50 mg/kg), 6, and 13 (10 mg/kg, respectively) post infection (p.i.). CD8⁺cells were depleted for up to 28 days p.i. in peripheral blood and LNs in all treated AGMs. Partial CD8⁺T cell depletion occurred in the intestine. SIVagm VLs peaked at similar levels in both groups (10⁷-10⁸RNA copies/ml). However, while VLs were controlled in undepleted AGMs, reaching set-point levels (10⁴-10⁵RNA copies/ml) by day 28 p.i., high VLs (>10⁶RNA copies/ml) were maintained by day 21 p.i. in CD8-depleted AGMs. By day 42 p.i., VLs were comparable between the two groups. The levels of immune activation and proliferation remained elevated up to day 72 p.i. in CD8-depleted AGMs and returned to preinfection levels in controls by day 28 p.i. None of the CD8-depleted animals progressed to AIDS.</p> <p>Conclusion</p> <p>CD8⁺cells are responsible for a partial control of postacute viral replication in SIVagm.sab-infected AGMs. In contrast to macaques, the SIVagm-infected AGMs are able to control viral replication after recovery of the CD8⁺T cells and avoid disease progression.</p

Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4+ T Cells and Is Reverted by CD8+ Cell Depletion

Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs) and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi) and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This “functional cure” of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status

Myroides injenensis Bacteremia and Severe Cellulitis

Myroides spp. are environmental bacterial organisms that rarely cause disease in humans. Myroides spp. infections are infrequently reported in the literature, and Myroides injenensis infections are quite uncommon. Myroides spp. usually infect immunocompromised hosts and can have highly resistant antibiotic susceptibility patterns. Here we report a case of Myroides injenensis bacteremia and severe cellulitis in a patient with cirrhosis and review the literature of other Myroides spp. infections

The importance of the microbiome in pediatrics and pediatric infectious diseases

Purpose of reviewEmerging research on the pediatric microbiome implicates the importance of the microbiome on the development of the immune system, nervous system, and growth. Changes to the microbiome during infancy are associated with the development of chronic illnesses such as asthma and inflammatory bowel disease. Additionally, the microbiome provides protection against certain pathogens, affects vaccine responses, and alters drug metabolism. This review highlights what is known about the microbiome, the establishment of a healthy microbiome and the significance that changes to the microbiome composition have on growth and health of children and adolescents.Recent findingsVaginal delivery, breastfeeding, maternal health, and nutrition help shape a healthy microbiome. Caesarian delivery, formula feeding, and antibiotic use perturb the microbiome and are associated with the development of type II diabetes, asthma, allergic diseases, and obesity later in life. Specific interventions using pre and probiotics in multiple settings are under investigation with limited success.SummaryA better understanding of the microbiome and the interaction with the immune system may help guide interventions to alter the microbiome toward a state of lifelong health

People with HIV Have Higher Risk of COVID-19 Diagnosis but Similar Outcomes than the General Population

Abstract: Background: We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and to comorbidity burden. Methods: Retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV IPWs), and combined models. Among PWH, we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did or did not develop study outcomes using receiver operating characteristic analysis. Results: Between March and November 2020, 63,319 people were receiving primary care services at UCSD, of whom 4,017 were people living with HIV (PWH). PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared to those without HIV after weighting for potential testing bias, comorbidity burden, and HIV-IPW (95% CI 1.6-2.8). Relative to persons without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR): 0.5, 95% CI: 0.1 – 1.4]. PWH had neither a different rate of ICU admission (aIRR:1.08, 95% CI; 0.31 – 3.80) nor in-hospital death (aIRR:0.92, 95% CI; 0.08 – 10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. Conclusions: PWH have a higher risk of COVID-19 diagnosis but similar outcomes compared to those without HIV. Summary point: After considering the effects of potential bias due to differential testing, comorbidities, and other patient characteristics, people with HIV had an increased rate of SARS-CoV-2 positivity and similar rates of hospitalization, ICU admission, and death

People with HIV have a higher risk of COVID-19 diagnosis but similar outcomes to the general population.

BackgroundWe investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and comorbidity burden.MethodsThis was a retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability-weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV-IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis.ResultsBetween March and November 2020, 63&nbsp;319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV-IPW [95% confidence interval (CI): 1.6-2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR)&nbsp;=&nbsp;0.5, 95% CI: 0.1-1.4]. PWH did not have a different rate of ICU admission (aIRR&nbsp;=&nbsp;1.08, 95% CI: 0.31-3.80) or of in-hospital death (aIRR = 0.92, 95% CI: 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH.ConclusionsPeople living with HIV have a higher risk of COVID-19 diagnosis than those without HIV but the outcomes are similar in both groups

Early Release - Antimicrobial-Resistant Shigella spp. in San Diego, California, USA, 2017–2020 - Volume 28, Number 6—June 2022 - Emerging Infectious Diseases journal - CDC

Annually, Shigella spp. cause ≈188 million cases of diarrheal disease globally, including 500,000 cases in the United States; rates of antimicrobial resistance are increasing. To determine antimicrobial resistance and risk factors in San Diego, California, USA, we retrospectively reviewed cases of diarrheal disease caused by Shigella flexneri and S. sonnei diagnosed during 2017-2020. Of 128 evaluable cases, S. flexneri was slightly more common than S. sonnei; most cases were in persons who were gay or bisexual cisgender men, were living with HIV, were unhoused, or used methamphetamines. Overall, rates of resistance to azithromycin, fluoroquinolones, ampicillin, and trimethoprim/sulfamethoxazole (TMP/SMX) were comparable to the most recent national data reported from the Centers for Disease Control and Prevention; 55% of isolates were resistant to azithromycin, 23% to fluoroquinolones, 70% to ampicillin, and 83% to TMP/SMX. The rates that we found for TMP/SMX were slightly higher than those in national data