Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients’ fibroblast phenotypes are rescued with WT IFNAR1. Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine–associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.

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Introduction: Multi-drug-resistant bacteria surveillance (MDR) systems are used to identify the epidemiology of MDR bacteria in neonates and children. This study aimed to describe the patterns by which MDR bacteria colonize and infect neonatal (NICU) and pediatric intensive care unit (PICU) patients in the state of Rio de Janeiro State, Brazil. Methods: A cross-sectional survey was performed using electronic data on NICU and PICU patients reported to the Rio de Janeiro State MDR bacteria surveillance system. All healthcare institutions that reported at least one case during the study period were included. Results: Between 2014 and 2017, 10,210 MDR bacteria cases, including 9261 colonizations and 949 infections, were reported. Among the colonizations, 5379 occurred in NICUs and 3882 in PICUs, while 405 infections occurred in NICUs and 544 in PICUs. ESBL producing Klebsiella sp and E. coli were the most reported colonization-causing agents in NICUs (1983/5379, 36.9%) and PICUs (1494/3882; 38.5%). The main causing bacteria reported in catheter-associated bloodstream infection (CLABSI), ventilator associated pneumonia, and catheter-associated urinary tract infection in NICUs were Klebsiella sp and E.coli (56/156, 35.9%), carbapenem-resistant Gram-negative bacteria (CRGNB) (22/65, 33.9%), and CRGNB (11/36, 30.6%) respectively, while in PICUs, they were MRSA (53/169, 31.4%), CRGNB (50/87, 57.4%), Klebsiella sp and E.coli (18/52, 34.6%), respectively. Conclusions: MDR Gram-negative bacteria (ESBL producers and carbapenem-resistant bacteria) were the most reported agents among MDR bacteria reported to Rio de Janeiro surveillance system. Except for CLABSI in children, they caused all deviceassociated infections in NICUs and PICUs.

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