Etiology

Murine typhus is caused by R. typhi, a rickettsia transmitted from infected fleas to rats, other rodents, or opossums and back to fleas. Transovarial transmission (passage of the organism from infected fleas to their progeny) in fleas is inefficient. Transmission depends on distribution by the flea to uninfected mammals that become transiently rickettsemic and transmit the organism to uninfected fleas.

Rickettsia felis is a novel agent species identified as a cause of a murine typhus-like illness worldwide. This new rickettsia is genetically a member of a transitional Rickettsia group and is capable of highly efficient transovarial transmission in cat fleas. This organism is found in cat fleas obtained from areas endemic for murine typhus in the USA and increasingly worldwide.

Epidemiology

Murine typhus has a worldwide distribution and occurs especially in warm coastal ports, where it is maintained in a cycle involving rat fleas (Xenopsylla cheopis) and rats (Rattus species). Peak incidence occurs when rat populations are highest during spring, summer, and fall. In the USA, the disease is most prevalent in south Texas and southern California, although seroprevalence studies among children indicate a higher than anticipated rate of infection broadly across the southeast and south-central USA, expanding the endemic areas in which pediatricians must be alert for this infection. In the coastal areas of south Texas, the disease is seen predominantly from March through June and is associated with opossums, cats, and cat fleas (Ctenocephalides felis).

Transmission

R. typhi normally cycles between rodents or mid-size animals such as opossums and their fleas. Human acquisition of murine typhus occurs when rickettsiae-infected flea feces contaminate flea bite wounds.

Pathology and Pathogenesis

R. typhi is a vasculotropic rickettsia that causes disease in a manner similar to R. rickettsii (Chapter 220.1). R. typhi organisms in flea feces deposited on the skin as part of the flea feeding reflex are inoculated into the pruritic flea bite wound. After an interval for local proliferation, the rickettsiae spread systemically to infect the endothelium in many tissues. As with spotted fever group rickettsiae, typhus group rickettsiae infect endothelial cells, but unlike the spotted fever group rickettsiae, they polymerize intracellular actin poorly, have limited intracellular mobility, and probably cause cellular injury by mechanical lysis after accumulating in large numbers within the endothelial cell cytoplasm. Intracellular infection leads to endothelial cell damage, recruitment of inflammatory cells, and vasculitis. The inflammatory cell infiltrates bring in a number of effector cells, including macrophages that produce proinflammatory cytokines, and CD4, CD8, and natural killer lymphocytes, which can produce immune cytokines such as interferon-γ or participate in cell-mediated cytotoxic responses. Intracellular rickettsial proliferation of typhus group rickettsiae is inhibited by cytokine-mediated mechanisms and nitric oxide–dependent and –independent mechanisms.

Pathologic findings include systemic vasculitis in response to rickettsiae within endothelial cells. This manifests as interstitial pneumonitis, meningoencephalitis, interstitial nephritis, myocarditis, and mild hepatitis with periportal lymphohistiocytic infiltrates. As vasculitis and inflammatory damage accumulate, multiorgan damage can ensue.

Clinical Manifestations