Lung nodules due to Candida parapsilosis in a person with cystic fibrosis.

We present the first reported case of Candida parapsilosis pulmonary infection presenting as lung nodules. The patient is a 31-year-old man with cystic fibrosis (CF) colonised with multidrug-resistant Escherichia coli and increased frequency of pulmonary exacerbations in the preceding months. While on intravenous antibiotics for a pulmonary exacerbation, he developed bilateral pulmonary nodules. Bronchoalveolar lavage cultures grew C. parapsilosis He was initially treated with dual antifungal therapy, voriconazole and micafungin. Discontinuation of voriconazole due to transaminitis resulted in the development of new nodules, and isavuconazonium was added. Repeat imaging revealed no progression of disease. Micafungin was eventually discontinued. Monotherapy with isavuconazonium is planned for 1 year post lung transplant. In the CF population, C. parapsilosis may be an opportunistic pathogen. The case highlights that frequent CF exacerbations and antibiotic exposure increase the risk for opportunistic infections including Candida species and the implications for lung transplantation in this setting.

B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies.

Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14-43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.