1021. Utility of Cell-Free DNA Sequencing in Diagnosing Murine typhus in Children

Background Murine typhus is a zoonotic infection caused by Rickettsia typhi and transmitted through infected fleas. Geographic distribution within the United States is limited primarily to South Texas and Southern California. Infection is typically associated with a triad of fever, headache, and rash, although is only present in one-third of cases. Immunofluorescence assay (IFA) is currently the gold standard for diagnosis, but it has its limitations as it is dependent on the time to seroconversion and has low specificity due to cross-reactivity among other rickettsial species. Cell-free DNA (cfDNA) sequencing for broad-range pathogen detection may offer higher sensitivity at the early stages of the disease. Methods We performed a retrospective electronic medical record search of children with cfDNA sequencing detection of Murine typhus hospitalized at Driscoll Children’s Hospital, Corpus Christi, Texas, between June 2020 and May 2021. Results We found 4 children (range 9-15 year-old) positive for R. typhi by cfDNA sequencing. All patients presented with fever of unknown origin and rash. Also, 2 patients were diagnosed with pneumonia. One patient exhibited severe illness with acute kidney injury, elevation of transaminases and encephalitis that warranted admission to the pediatric intensive care unit. All patients defervesced and improved within 48 hours of doxycycline initiation; average length of stay 6 days (range 3-12 days). In one patient, M. typhus was detected by Karius® test only, in the other three was concordant with serology. Conclusion We highlight next-generation cfDNA sequencing as a useful tool in identifying the etiologic agent of patients with fever of known origin, where murine typhus is one of the possible etiologies. Preventing extensive laboratory workup and subsequent delay of assessment and management. The rapid turnaround time of cfDNA test allows for de-escalation of therapy and initiation of appropriate treatment. Disclosures Jaime Fergie, MD, AstraZeneca (Scientific Research Study Investigator)Explify (Speaker’s Bureau)Karius (Speaker’s Bureau)Pfizer, Merck, AstraZeneca, and Sanofi (Speaker’s Bureau)Pfizer, Merck, Sanofi, and Moderna (Consultant, Advisor or Review Panel member)

A spatio-temporal analysis of scrub typhus and murine typhus in Laos; implications from changing landscapes and climate

Background Scrub typhus (ST) and murine typhus (MT) are common but poorly understood causes of fever in Laos. We examined the spatial and temporal distribution of ST and MT, with the intent of informing interventions to prevent and control both diseases. Methodology and principle findings This study included samples submitted from 2003 to 2017 to Mahosot Hospital, Vientiane, for ST and MT investigation. Serum samples were tested using IgM rapid diagnostic tests. Patient demographic data along with meteorological and environmental data from Laos were analysed. Approximately 17% of patients were positive for either ST (1,337/8,150 patients tested) or MT (1,283/7,552 patients tested). While both diseases occurred in inhabitants from Vientiane Capital, from the univariable analysis MT was positively and ST negatively associated with residence in Vientiane Capital. ST was highly seasonal, with cases two times more likely to occur during the wet season months of July-September compared to the dry season whilst MT peaked in the dry season. Multivariable regression analysis linked ST incidence to fluctuations in relative humidity whereas MT was linked to variation in temperature. Patients with ST infection were more likely to come from villages with higher levels of surface flooding and vegetation in the 16 days leading up to diagnosis. Conclusions The data suggest that as cities expand, high risk areas for MT will also expand. With global heating and risks of attendant higher precipitation, these data suggest that the incidence and spatial distribution of both MT and ST will increase.

Neglected human Rickettsia felis infection in Taiwan: A retrospective seroepidemiological survey of patients with suspected rickettsioses

Background Current knowledge on Rickettsia felis infection in humans is based on sporadic case reports. Here we conducted a retrospective seroepidemiological survey of R. felis infection among febrile patients visiting a medical center in Taipei. Methodology/Principal findings A total of 122 patients with suspected rickettsioses presenting with fever of unknown origin (FUO) but tested negative for scrub typhus, murine typhus, or Q fever were retrospectively identified during 2009 to 2010. The archived serum samples were examined for the presence of antibodies against R. felis, Rickettsia japonica, and Rickettsia typhi using microimmunofluorescence (MIF) assay. Serological evidence of Rickettsia exposure was found in 23 (19%, 23/122) patients. Eight patients had antibodies reactive to R. felis, including four with current infection (a ≥4-fold increase in IgG titer between acute and convalescent sera). The clinical presentations of these four patients included fever, skin rash, lymphadenopathy, as well as more severe conditions such as pancytopenia, hepatomegaly, elevated liver enzymes/bilirubin, and life-threatening acute respiratory distress syndrome. One of the patients died after doxycycline was stopped after being tested negative for scrub typhus, Q fever, and murine typhus. Conclusions Rickettsia felis is a neglected flea-borne pathogen in Taiwan, and its infection can be life-threatening. Further prospective studies of the prevalence of R. felis among patients with FUO and compatible clinical manifestations are warranted.

Sunbathing, a possible risk factor of murine typhus infection in Greece

Background There are few studies about the presence of murine typhus in Greece. Our objective was to conduct a large scale retrospective investigation to determine the clinical and epidemiological features of patients diagnosed with murine typhus in Greece. Methodology/Principal findings From 2012 to 2019 serum samples from hospitalized patients and outpatients throughout Greece suspected for murine typhus infection were tested by immunofluorescence assay for Rickettsia typhi. Immunofluorescence positive samples obtained since 2016 were also tested by qPCR targeting R. typhi. Clinical and epidemiological data were retrospectively collected for the patients with confirmed murine typhus. Overall, we tested 5,365 different patients and, in total, 174 patients from all geographic regions of Greece were diagnosed with murine typhus. The most frequently reported sign or symptom was fever (89%), followed by headache (84%) and rash (81%). The classical triad of fever, headache, and rash was present in 72% of patients during their illness. Severe infections with complications including acute renal failure or septic shock were not recorded. The majority of cases (81%) occurred during May–October and peaked in June and September. Most of patients (81%) infected in Athens, recalled that their only activity the last weeks before symptoms onset was swimming on the beach and 59% of them also reported an insect bite while sunbathing. Conclusions/Significance Our results may reflect the reemergence of murine typhus in Greece and we highlight the importance of awareness of this difficult-to-recognize undifferentiated febrile illness.