Typhus Group Rickettsioses

Keywords

• murine typhus

• endemic typhus

• flea-borne typhus

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 infection from the flea to uninfected mammals that then sustain transient rickettsemia and serve as sources of the bacterium for uninfected fleas that bite during the period of rickettsemia.

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. Sentinel surveillance studies suggest that travel-acquired murine typhus occurs most often in those visiting Southeast Asia and Africa. In the United States, the disease is recognized most often in south Texas and Southern California. However, seroprevalence studies among children indicate that murine typhus is acquired across the southeast and south-central United States, thus expanding the endemic areas in which pediatricians must be alert for this infection. In the coastal areas of south Texas and in Southern California, the disease is seen predominantly from March through June and is associated with a sylvatic cycle involving opossums and cat fleas (Ctenocephalides felis) .

Transmission

R. typhi normally cycles between rodents or midsize animals such as opossums and their fleas. Human acquisition of murine typhus occurs when rickettsiae-infected flea feces contaminate flea bite wounds. Direct inoculation via flea bite is possible, but inefficient.

Pathology and Pathogenesis

R. typhi is a vasculotropic rickettsia that causes disease in a manner similar to Rickettsia rickettsii (see Chapter 255.1 ). 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 via lymphatics to the blood, after which they 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 either enzymatic membrane or 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 vasculitis 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

In children, murine typhus is a generally a self-limited infection, but can be severe, similar to other vasculotropic rickettsioses. The incubation period varies from 1 to 2 wk. The initial presentation is often nonspecific and mimics typhoid fever; fever of undetermined origin is the most common presentation. Pediatric patients with murine typhus exhibit symptoms classically attributed to other vasculotropic rickettsioses, such as rash (48–80%), myalgias (29–57%), vomiting (29–45%), cough (15–40%), headache (19–77%), and diarrhea or abdominal pain (10–40%). A petechial rash is observed in <15% of children, and the usual appearance is that of macules or maculopapules distributed on the trunk and extremities. The rash can involve both the soles and palms. Among common clinical features, only abdominal pain, diarrhea, and sore throat are more common in children than in adults, underscoring the mild nature of most cases in children. Murine-typhus associated hemophagocytic syndrome was recently described. Although neurologic involvement is a common finding in adults with murine typhus, photophobia, confusion, stupor, coma, seizures, meningismus, and ataxia are seen in <20% of hospitalized children and <6% of infected children treated as outpatients. Poor neonatal outcomes are reported with infection during pregnancy; however, both the frequency and clinical spectrum are not well documented.