Severe Arboviral Neuroinvasive Disease in Patients on Rituximab Therapy: A Review.

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days to 1 year), and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

Identification of Multiple Variant Extensively Drug-Resistant Typhoid Infections across Pakistan.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening bacterial infection. Recently, an outbreak of a new sublineage of extensively drug resistant (XDR) S. Typhi emerged in Pakistan in the province of Sindh. This sublineage had both a composite multidrug resistance transposon integrated on the chromosome and an acquired IncY plasmid carrying the extended spectrum beta-lactamase, blaCTX-M-15, which conferred resistance to third-generation cephalosporins. We observed previously that XDR typhoid had spread beyond the originating southern Sindh Province. Thus, we sought to determine the genetic diversity of 58 ceftriaxone-resistant S. Typhi clinical isolates by whole genome sequencing collected across Pakistan from November 2018 to December 2020 to provide insights into the molecular epidemiology of the evolving outbreak. We identify multiple novel genomic integrations of the extended spectrum beta-lactamase gene into the chromosome in S. Typhi, revealing the existence of various XDR typhoid variants circulating in the country. Notably, the integration of the IncY plasmid bearing antibiotic resistance genes may allow for subsequent plasmid acquisition by these variants, potentially leading to further plasmid-borne multidrug resistance. Our results can inform containment initiatives, help track associated outcomes and international spread, and help determine how widespread the risk is.