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Molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. Mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. Here, we compared the genetic diversity of the bacteria that established infection to the bacterial populations obtained from infected tissues during murine M. tuberculosis pulmonary infection and human disseminated M. bovis BCG infection. We found that new mutations accumulate during in vitro culture, but that in vivo, purifying selection against new mutations dominates, indicating that M. tuberculosis follows a dominant lineage model of evolution. Comparing bacterial populations passaged in T cell-deficient and immunocompetent mice, we found that the presence of T cells is associated with an increase in the diversity of the M. tuberculosis genome. Together, our findings put M. tuberculosis genetic evolution in a new perspective and clarify the impact of T cells on sequence diversity of M. tuberculosis.

A recent surge in this disease has prompted health advisories by the US Centers for Disease Control and Prevention (CDC),1 the Royal College of Paediatrics and Child Health,2 and WHO.3 As SARS-CoV-2 spreads and awareness of MIS-C grows, the number of reported cases continues to increase. Complete blood counts showed leukocytosis (11 600–16 500 white blood cells per μL), with lymphopenia (0–700 lymphocytes per μL), neutrophilia (10 100–15 000 neutrophils per μL), atypical lymphocytosis (2% atypical lymphocytes), and increased band neutrophils (2–16% band cells), whereas comprehensive metabolic panels showed hyponatraemia (serum sodium 124–135 mmol/L) and elevated hepatic enzymes (aspartate aminotransferase [AST] 96–198 U/L; alanine aminotransferase 78–133 U/L). Emerging reports have revealed a pattern of clinical differences distinguishing MIS-C from classic Kawasaki disease.5–9 Notably, although our patient's presentation met AHA criteria for Kawasaki disease, he also exhibited many MIS-C-related features such as a predominance of gastrointestinal symptoms, generalised extremity pain, and prominent cardiac dysfunction, and his cardiac findings (elevated cardiac enzymes and left ventricular hypokinesis with a reduction in ejection fraction) resemble findings of myocarditis recently described in MIS-C.10 Furthermore, our patient's palmar lesions are distinct from the acral erythema and swelling with subsequent desquamation typically seen in Kawasaki disease, and his diffuse conjunctivitis was not limbic-sparing.

We describe a case of a 72-year-old man with early-stage chronic lymphocytic leukemia (CLL) who presented with invasive nontyphoidal Salmonella (iNTS) infection, necrotizing pneumonia, and chronic infection of a hilar lymph node. Infection is a major cause of death in patients with CLL. Though few cases of iNTS infection associated with CLL have been described in the literature, to our knowledge this is the first reported case of iNTS-associated necrotizing pneumonia. Immunocompromised state in patients, even with early-stage CLL, likely predisposes them to invasive infection with intracellular organisms, such as Salmonella spp. In this case, successful treatment was achieved with prolonged course of intravenous followed by oral antibiotics without any surgical removal of infected focus.

Hepatitis is an unusual manifestation of herpesvirus infection. Herpes simplex virus hepatitis is a difficult diagnosis to establish, and the infection is often fatal. We report one case of herpes simplex virus hepatitis and review 51 cases in the literature. Impaired immunity resulting from pregnancy, malignancy, immunosuppression, or inhalational anesthetics may be predisposing factors. Fever, nausea, vomiting, abdominal pain, leukopenia, thrombocytopenia, coagulopathy, and a marked rise in serum transaminase levels are invariably present. Liver biopsy is the procedure of choice for diagnosis. The liver appears mottled and has a minimal inflammatory response. Mortality rates associated with herpes simplex virus hepatitis are high, and early diagnosis and treatment with acyclovir or vidarabine may produce a favorable outcome.

Abstract Background Patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) have poor outcomes and frequently develop comorbid conditions, including cytomegalovirus (CMV) reactivation. The implications of CMV reactivation in this setting are unknown. We aimed to investigate if treatment of CMV viremia improved in-hospital mortality in ICU patients with COVID-19. Methods In this single-center retrospective study, we analyzed clinical outcomes in patients diagnosed with COVID-19 pneumonia and CMV viremia admitted to an ICU from March 1, 2020, to April 30, 2021, who either received treatment (ganciclovir and/or valganciclovir) or received no treatment. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were total hospital length of stay (LOS), ICU LOS, requirement for extracorporeal membrane oxygenation (ECMO) support, duration of mechanical ventilation (MV), and predictors of in-hospital mortality. Results A total of 80 patients were included, 43 patients in the treatment group and 37 in the control group. Baseline characteristics were similar in both groups. CMV-treated patients were more likely to test positive for CMV earlier in their course, more likely to be on ECMO, and received higher total steroid doses on average. In-hospital mortality was similar between the 2 groups (37.2% vs 43.2.0%; P = .749). There was no significant difference in hospital LOS, though CMV-treated patients had a longer ICU LOS. Conclusions Treatment of CMV viremia did not decrease in-hospital mortality in ICU patients with COVID-19, but the sample size was limited. CMV viremia was significantly associated with total steroid dose received and longer ICU stay.

Treatment of Legionnaires’ disease in severely ill or immunosuppressed patients presents a clinical challenge. Tigecycline (TG) achieves high concentrations intracellularly and has been shown to be effective against L. pneumophila in animal and cell models. We report our experience using TG as second-line therapy. Clinical response was seen in most patients after switching to TG alone or as a combination therapy.

To the Editor: The earliest trial of zidovudine (Retrovir; formerly called azidothymidine, or AZT) in the treatment of human infections with human immunodeficiency virus began in 1985. Nearly 9000 persons with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex have received this drug, which has been shown to reduce the incidence of death and opportunistic infections.* Its principal toxic effects are macrocytic anemia, neutropenia, and various constitutional symptoms. No cases of a polymyositis-like syndrome associated with zidovudine have been reported to the manufacturer of the drug (Collins E: personal communication). We have observed four patients receiving long-term zidovudine therapy who had . . .

The heart infection called endocarditis can be a deadly matter. Guarding against it requires steady vigilance by doctors and patients. Those who have to worry about endocarditis are a diverse group that includes children with congenital heart defects, patients with artificial heart valves, and persons with heart murmurs or abnormalities of heart valves, including some cases of mitral valve prolapse, a cardiac condition more common in women than men.