Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection.

There are sufficient data demonstrating that coexisting conditions in patients with Covid-19 influence clinical outcomes and that older age and male sex are associated with a greater risk of death. But despite disproportionately higher rates of Covid-19 infection, hospitalization, and death in racial and ethnic minority groups, the direct effects of genetic or biologic host factors remain unknown.¹

Chagas disease is a complex parasitic zoonosis that still threatens public health across the Americas. Initiatives to control Trypanosoma cruzi transmission via blood transfusion and non-native triatomine-bug vectors have yielded crucial advances; native vectors, however, actively bridge wild and domestic/peri-domestic transmission cycles throughout the region, and tens of thousands of people become infected each year. Oral-transmission outbreaks, urbanisation, and vertical transmission are additional/emerging issues calling for innovative strategic thinking. While critical for advocacy and sustained public health action, assessing Chagas disease burden remains difficult; the often-asymptomatic nature of T. cruzi infection, healthcare access limitations, pervasive underreporting, and other methodological hurdles inherent to reliably measuring incidence, prevalence, and disease progression all contribute to the difficulty. Whether and how parasite, vector, and host genetic makeups affect transmission dynamics and epidemiology is also unclear. Continued high-quality research and long-term, adaptive strategies combining vector control surveillance with enhanced case detection and integral patient care remain critical to effectively address the ethical and societal challenge of Chagas disease control.

Sepsis is a global health challenge associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to excessive inflammation or a "cytokine storm." However, anti-inflammation therapies have failed to lower sepsis mortality. We aim to characterize levels of key inflammatory cytokines in patients with sepsis and compare levels with those in healthy individuals and relate tumor necrosis factor (TNF) α levels to patient characteristics and outcomes. We performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched between 1985 and May 2020. Analysis was restricted to studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy individuals. The Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800). We identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8-85.8 pg/ml), and in healthy individuals was 5.5 pg/ml (95% CI 3.8-8.0 pg/ml). Pooled estimate means for IL-1β and IFN-γ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p = 0.001). In subgroup analyses, we did not detect an association between TNFα levels and sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score. A TNF-α cutoff level ≥14.7 pg/ml separated sepsis patients from healthy individuals with a sensitivity of 82.6%, a specificity of 91.7%, and a likelihood ratio of 9.9. Sepsis mean TNFα concentration is increased approximately 10-fold compared to mean concentration in healthy individuals, and TNFα associated with sepsis mortality but not sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data. None.

Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased susceptibility to infections are widely appreciated. However, the dose-dependent model frequently used may not accurately predict the risk of infection in all patients treated with long-term glucocorticoids. In this review, we examine the risks of opportunistic infections (OIs) in patients requiring glucocorticoid therapy by evaluating the influence of the glucocorticoid dose, duration, and potency, combined with biological and host clinical factors and concomitant immunosuppressive therapy. We propose strategies to prevent OIs, which involve screening, antimicrobial prophylaxis, and immunizations. While this review focuses on patients with autoimmune, inflammatory, or neoplastic diseases, the potential risks and preventative strategies are likely applicable to other populations. Clinicians should actively assess the benefit–harm ratios of systemic glucocorticoids and implement preventive efforts to decrease their associated infections complications.