The impact of sex hormones on BCG-induced trained immunity.

The anti-tuberculosis vaccine Bacillus Calmette-Guérin (BCG) is a well-known immune modulator that induces nonspecific protective effects against heterologous infections through induction of innate immune memory, also termed "trained immunity." In randomized trials in low weight newborns, BCG vaccination reduced neonatal mortality due to decreased incidence of sepsis and respiratory infections. In many studies, sex-differential nonspecific effects of vaccines have been observed, but the mechanisms behind these differential effects are unknown. We investigated whether the important sex hormones estrogen and dihydrotestosterone (DHT) influence BCG-induced trained immunity in human primary monocytes. Although addition of estradiol and DHT to BCG inhibited the production of proinflammatory cytokines after direct stimulation of human monocytes, they did not influence the induction of trained immunity by BCG. In addition, estradiol or DHT did not induce training or tolerance in monocytes themselves. We conclude that these important sex hormones are unlikely to explain the sex-differential effects after BCG vaccination. Future studies should focus on the investigation of alternative mechanisms as an explanation for sex-differential nonspecific effects of BCG vaccination.

Non-specific effects of vaccines: Current evidence and potential implications.

Besides protection against specific microorganisms, vaccines can induce heterologous or non-specific effects (NSE). Epidemiological data suggest that vaccination with live-attenuated vaccines such as Bacillus Calmette-Guérin (BCG), measles vaccine, and oral polio vaccine results in increased overall childhood survival, and several of these observations have been confirmed in randomized trials. Immunological mechanisms mediating NSE include heterologous lymphocyte effects and induction of innate immune memory (trained immunity). Trained immunity induces long-term functional upregulation of innate immune cells through epigenetic and metabolic reprogramming. An overview of the epidemiological evidence of non-specific effects of vaccines and the latest insights regarding the biological mechanisms behind this phenomenon is presented, and future research priorities and potential implications are discussed.

Spontaneous fracture of the femur due to osteomyelitis caused by the Streptococcus anginosus group.

A 57-year-old man was admitted because of pain in the right upper leg due to an osteolytic lesion of the femoral bone which was complicated by a spontaneous fracture. At first a malignancy was suspected. However, blood and bone cultures revealed the Streptococcus anginosus group. A diagnosis of acute osteomyelitis was made. In spite of extensive antibiotic and surgical treatment the patient developed severe septic shock with multiple organ failure and died. In the case of a pathological fracture, one should consider the broad differential diagnosis, including osteomyelitis, which should lead to a laboratory work-up and imaging studies. When bone biopsy for histological analysis is necessary, a microbiological culture to look for osteomyelitis should always be performed.

MRSA as a rare cause of vaginitis.

We describe a 26-year-old otherwise healthy woman with MRSA vaginitis. Traditional MRSA risk factors were absent and additional screening sites were negative. Patient was treated successfully with oral antibiotics combined with topical lactic acid emulsion. Because her partner appeared to have solitary MRSA carriage on the glans, a suggestion of sexual transmission was made. He was treated successfully with topical mupirocin ointment. Although solitary vaginal MRSA carriage and infection seems to be rare and its clinical impact is yet undefined, clinicians should consider adding the genitourinary tract to traditional screening sites in case of recurrent MRSA infections.

Fasciola hepatica as a cause of jaundice after chewing khat: a case report.

Fasciola hepatica is a worldwide distributed zoonotic trematode incidentally infecting humans. Although often symptomatic, fascioliasis can cause a wide spectrum of disease. The diagnosis can be established by stool examination detecting ova of the parasite, although serological testing has a higher sensitivity and specificity in the acute phase of disease. This case presents a 24-year-old Somalian man admitted with jaundice and abdominal discomfort due to fascioliasis after chewing khat. The patient was treated successfully with a single dose of triclabendazole.