Murine typhus (also called flea-borne or endemic typhus) is an undifferentiated febrile illness caused by the bacterium Rickettsia typhi. The disease, transmitted by rat and cat fleas, is endemic to seaboard regions worldwide. Recently, murine typhus has reemerged as an increasingly recognized cause of febrile illness in the United States, especially in Texas and Southern California. In addition to fever, manifestations often include headache, malaise, myalgias, and a maculopapular rash in approximately half of cases. Although usually considered a mild illness, when untreated, symptoms can last up to 3 weeks. Severe manifestations such as pneumonitis, acute kidney injury, and meningoencephalitis may occur. Historically, death has occurred in 0.4%, but in Southern California, the case fatality rate has been recently recorded at 1.8%. As murine typhus has reemerged, there have been growing reports that this infection has triggered hemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome. We herein report two fatal cases of hemophagocytic lymphohistiocytosis secondary to murine typhus. Autopsy revealed typhus group rickettsial antigen in tissues via immunohistochemistry, along with hemophagocytosis. Interestingly, the classic vascular and perivascular histopathologic findings associated with disseminated rickettsial infection were absent. These findings highlight an aberrant inflammatory cascade leading to hemophagocytic lymphohistiocytosis.

Typhus group rickettsiosis (TGR), caused by Rickettsia typhi and Rickettsia prowazekii, are globally distributed vector-borne diseases with increasing cases. Diagnosis is usually clinical, confirmed by seroconversion of IgG antibodies. Human infection occurs in diverse geographic areas with some developing CNS infection characterized by fever, headache, meningismus, and/or focal signs - usually beyond the first week of initial symptomatology. Seizures and other CNS manifestations have been observed. When untreated, infection may result in neurologic sequelae and even death. This study presents a systematic review of all documented cases of Rickettsia typhi meningoencephalitis published since 2015 with the addition of five cases of TGR in South Coastal Texas, USA. This review followed the guidelines outlined in PRISMA. A schematic explanation of the pathophysiology is offered. CSF may present with high opening pressure, mild to moderate pleocytosis, mildly elevated protein levels, and low csf/serum glucose ratio, or normal findings. Meningeal enhancement, intracranial hypertension, and focal abnormalities have been described in imaging studies, but can be normal. Treatment with doxycycline leads to prompt resolution of symptoms. Failure to initiate early empiric treatment can lead to serious consequences. The study recommends routine testing for TGR in patients from endemic areas with classical symptoms when other diagnoses are inconclusive or in cases with atypical presentations. The authors advocate for incorporating empiric treatment for murine typhus into community-acquired bacterial meningitis guidelines in endemic areas; and stress the importance of enhancing laboratory diagnostic capabilities in public health entities world-wide. Further studies of community acquired mengingoencephalitis caused by TGR are highly encouraged.

We conducted a systematic analysis of the notifiable rickettsial diseases in humans in China during 1950-2022. We utilized descriptive statistics to analyze the epidemiological characteristics, clinical manifestations, and diagnostic characteristics of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases. Since the 1950s, there have been variations in the incidence rate of TGR and ST in China, with a downtrend for TGR and an uptrend for ST. The South became a high-incidence area of TGR, whereas the North was previously the high-incidence area. ST cases were concentrated in the South and the geographic area of ST spread northward and westward. The seasonality of TGR and ST were similar in the South but distinct in the North. Most TGR and ST cases were reported by county-level medical institutions, whereas primary institutions reported the least. Delayed diagnosis was associated with fatal outcomes of TGR and ST. Cases in low-incidence provinces, confirmed by laboratory tests and reported from county/municipal-level institutions had higher odds of delayed diagnoses. Our study revealed significant changes in the epidemiological characteristics of TGR and ST in China, which can provide useful information to enhance the control and prevention strategies of rickettsial diseases in China.

Whether increases in typhus group rickettsiosis in Galveston County, Texas, USA, are caused by increased recognition or true reemergence is unclear. We conducted a serosurvey that demonstrated Rickettsia typhi antibodies increased from 1.2% in 2013 to 7.8% in 2021 (p<0.001). These findings support pathogen reemergence rather than enhanced recognition alone.